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@#Type 2 diabetes mellitus(T2DM)was a chronic,non-communicable disease with a combination of multiple genetic and environmental factors,of which the main characteristics included insufficient insulin secretion and insulin resistance.Insulin-like growth factor 2 mRNA binding protein 2(IGF2BP2/IMP2),an important insulin secretion-related protein in human body,is mainly expressed in tissues and cells such as pancreas,fat and intestine.It has been confirmed that IGF2BP2 can down-regulate the expression of IGF2 and the function damage of the related islet β cell is an important cause of T2DM and vascular complications.Therefore,IGF2BP2 gene can be used as an important predictor for diabetes mellitus risk.This paper reviews the correlation between IGF2BP2 gene and T2DM.
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Type 2 diabetes mellitus （T2DM） is a heterogeneous disease with insulin deficiency and insulin resistance （IR） as the main etiology and is often accompanied by complications. Volatile oil is a volatile oily liquid extracted from natural plants， which has many pharmacological effects such as regulating Qi， relieving pain， inhibiting bacteria， and reducing inflammation. In recent years， there have been numerous reports on the treatment of T2DM by natural plant volatile oil and its effective components， which has become one of the new directions in the treatment of T2DM. With natural plant essential oil and its active components as the starting point， this paper comprehensively analyzed and summarized the material basis， mechanism， and signaling pathways of essential oil in the treatment of T2DM and its complications in China and abroad in recent years， and focused on the inhibitory effect of essential oil and its active components， such as carvacrol， paeonol， and β-caryophylene， on IR to improve T2DM by protecting pancreatic β-cells， inhibiting α-glucosidase activity， regulating the abundance and diversity of intestinal microbiota， and regulating glucose transporter protein type4 （GLUT4）， adenylate 5′-monophosphate-activated protein kinase （AMPK）， phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt） signaling pathways to provide some references for the volatile oil intervention in T2DM and the development of new green antidiabetic drugs.
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OBJECTIVE@#To observe the hypoglycemic effect of electroacupuncture (EA) at "Tianshu" (ST 25) combined with metformin on rats with type 2 diabetes mellitus (T2DM) as well as its effect on expression of adenosine monophosphate activated protein kinase (AMPK) in liver and pancreas.@*METHODS@#Thirty-six male SD rats were randomly divided into a blank group (6 rats) and a model establishing group (30 rats). The rats in the model establishing group were fed with high-fat diet and treated with intraperitoneal injection of low-dose streptozotocin (STZ) to establish T2DM model. The rats with successful model establishment were randomly divided into a model group, a control group, a metformin group, an EA group and a combination group, 6 rats in each group. The rats in the EA group were treated with EA at "Tianshu" (ST 25), dense-disperse wave, 2 Hz/15 Hz in frequency and 2 mA in current intensity, 20 min each time. The rats in the metformin group were treated with intragastric administration of metformin (190 mg/kg) dissolved in 0.9% sodium chloride solution (2 mL/kg). The rats in the combination group were treated with EA at "Tianshu" (ST 25) and intragastric administration of metformin. The rats in the control group were treated with intragastric administration of 0.9% sodium chloride solution with the same dose. All the treatments were given once a day for 5 weeks. After the intervention, the body mass and random blood glucose were detected; the serum insulin level was detected by ELISA; the expression of AMPK and phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) in liver and pancreas was detected by Western blot method; the expression of protein gene product 9.5 (PGP9.5) was detected by immunofluorescence.@*RESULTS@#①Compared with the blank group, the body mass in the model group was decreased (P<0.05); compared with the model group, the body mass in the EA group and the combination group was decreased (P<0.05); the body mass in the EA group and the combination group was lower than the metformin group (P<0.05). Compared with the blank group, the random blood glucose in the model group was increased (P<0.01); compared with the model group, the random blood glucose in the metformin group, the EA group and the combination group was decreased (P<0.01). The random blood glucose in the combination group was lower than the metformin group and the EA group (P<0.05). ②Compared with the blank group, the insulin level in the model group was decreased (P<0.05); compared with the model group, the insulin level in the metformin group, the EA group and the combination group was all increased (P<0.05). The insulin level in the combination group was higher than the metformin group and the EA group (P<0.05). ③Compared with the blank group, the protein expression of AMPK and p-AMPK in liver tissue was decreased (P<0.05), and the protein expression of AMPK and p-AMPK in pancreatic tissue was increased (P<0.05) in the model group. Compared with the model group, the protein expression of AMPK and p-AMPK in liver tissue in the metformin group, the EA group and the combination group was increased (P<0.05, P<0.01); the protein expression of AMPK in pancreatic tissue in the metformin group was increased (P<0.05); the protein expression of AMPK in pancreatic tissue in the EA group and the combination group was decreased (P<0.05); the protein expression of p-AMPK in pancreatic tissue in the metformin group, the EA group and the combination group was decreased (P<0.05). The protein expression of AMPK and p-AMPK in liver tissue in the combination group was higher than that in the metformin group and the EA group (P<0.05); the protein expression of AMPK in pancreatic tissue in the EA group and the combination group was less than that in the metformin group (P<0.05), and the expression of p-AMPK protein in pancreatic tissue in the combination group was less than that in the metformin group and the EA group (P<0.05). ④Compared with the blank group, the expression of PGP9.5 in pancreatic tissue in the model group was increased (P<0.01); compared with the model group, the expression of PGP9.5 in pancreatic tissue in the metformin group, the EA group and the combination group was decreased (P<0.05, P<0.01). The expression of PGP9.5 in pancreatic tissue in the EA group was lower than the metformin group and the combination group (P<0.05).@*CONCLUSION@#Electroacupuncture at "Tianshu" (ST 25) could promote the effect of metformin on activating AMPK in liver tissue of T2DM rats, improve the negative effect of metformin on AMPK in pancreatic tissue, and enhance the hypoglycemic effect of metformin. The mechanism may be related to the inhibition of pancreatic intrinsic nervous system.
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Animals , Male , Rats , Acupuncture Points , AMP-Activated Protein Kinases/genetics , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Electroacupuncture , Hypoglycemic Agents , Insulins , Metformin , Rats, Sprague-DawleyABSTRACT
ObjectiveTo investigate the effect of Dendrobii Caulis mixture on cell inflammatory response and apoptosis in diabetic rat with non-alcoholic fatty liver disease（NAFLD） and its possible mechanism. MethodForty male SD rats were randomly divided into blank group and model group of type 2 diabetes mellitus（T2DM） with NAFLD according to body weight. The model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ）， which was randomly divided into the model group， Dendrobii Caulis mixture group（16.67 g·kg-1·d-1） and metformin group（100 mg·kg-1·d-1） according to blood glucose and body weight， and 10 rats in each group. Rats in each group were administered by continuous gavage for 4 weeks， the blank and model groups were given saline by gavage at 10 mL·kg-1·d-1. Fasting blood glucose（FBG）， serum insulin（INS）， glycosylated serum protein（GSP）， triglyceride（TG）， total cholesterol（TC）， high density lipoprotein（HDL-C）， low density lipoprotein（LDL-C）， alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were detected in each group of rats. The liver tissues of rats in each group were stained with hematoxylin-eosin（HE） to observe the pathological changes， and the positive expressions of nuclear transcription factor（NF）-κB， NOD-like receptor heat protein structural domain-related protein 3（NLRP3）， interleukin（IL）-1β and tumor necrosis factor（TNF）-α were observed by immunohistochemistry. Western blot and fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of B-cell lymphoma-2（Bcl-2）， Bcl-2 associated X protein（Bax）， Caspase-3 and NF-κB p65， NLRP3， IL-1β， TNF-α in liver tissue of rats in each group. ResultCompared with the blank group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels were increased， INS and HDL-C levels were decreased， Bax， Caspase-3， NLRP3， IL-1β， TNF-α protein and mRNA expression were increased in model group， the ratio of p-NF-κB/NF-κB protein increased， the expression of Bcl-2 protein and mRNA decreased， and the positive immunohistochemical expression of NF-κB， NLRP3， IL-1β and TNF-α increased， and the differences were statistically significant（P<0.01）. The morphological structure of the liver was disrupted， and obvious fat vacuoles were seen. Compared with the model group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels of Dendrobii Caulis mixture group and metformin group were decreased， INS and HDL-C levels were increased， and protein and mRNA expressions of Bax， Caspase-3， NLRP3， IL-1β and TNF-α were decreased， the protein ratio of p-NF-κB/NF-κB decreased， the expression of Bcl-2 protein and mRNA increased， and the positive immunohistochemical expressions of NF-κB， NLRP3， IL-1β and TNF-α decreased， and the differences were statistically significant（P<0.01）. The liver morphology and structure were relatively complete， and the fat vacuoles were reduced. ConclusionDendrobii Caulis mixture can inhibit cell apoptosis， reduce inflammatory response and alleviate liver injury in rats with T2DM and NAFLD， the mechanism may be related to inhibiting the activation of NF-κB pathway， blocking the activation of NLRP3 inflammatory vesicles， reducing IL-1β secretion， attenuating Caspase-3 activity and reducing the ratio of Bcl-2/Bax.
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Abstract The insertion of Pharmaceutical Care in Primary Health Care (PHC) improves patients' clinical outcomes and quality of life. Pharmacotherapeutic follow-up can contribute to the management of chronic diseases such as diabetes, promoting better glycemic control and adherence to therapy. This study aimed to assess the Drug-therapy Problems (DTPs) and Pharmacist Interventions (PIs) on the pharmacotherapeutic management in patients with type 2 diabetes mellitus (T2DM) in a community pharmacy. A quantitative, retrospective, and cross-sectional study was conducted in a Pharmaceutical Care Program within the PHC in Juiz de Fora (Minas Gerais, Brazil). Inclusion criteria were patients with T2DM above 18, who attended at least three pharmaceutical consultations between July 2016 and October 2018 and presented two or more glycated hemoglobin tests. The study group (n = 17) was largely composed of women (65%), elderly (76%), sedentary (72%), and obese people (52%). The resolution was achieved in 79% of the DTPs identified (n = 115). Most of DTPs were related to administration and adherence to pharmacotherapy (46%). 60% of the 437 PIs involved the provision of information and counseling. In other words, accessible interventions lead to high resolvability. Therefore, clinical actuation of pharmacists could improve the prognosis in diabetes treatment
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Humans , Male , Female , Adolescent , Adult , Aged , Patients/classification , Pharmaceutical Services/organization & administration , Primary Health Care/organization & administration , Diabetes Mellitus, Type 2/pathology , Pharmacies/classification , Referral and Consultation/standards , Chronic Disease/drug therapy , Cross-Sectional Studies/instrumentation , Pharmacoepidemiology/instrumentation , Drug Therapy/classificationABSTRACT
ObjectiveTo explore the mechanism of herbal pair Astragali Radix-Puerariae Lobatae Radix （AR-PLR） against type 2 diabetes mellitus （T2DM） based on network pharmacology and experimental verification. MethodThe active ingredients and targets of AR and PLR were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The related targets of T2DM were retrieved from disease databases and the common targets of drugs and diseases were extracted. The protein-protein interaction （PPI） network was analyzed and constructed by STRING and the network topology of key targets was analyzed by Cytoscape 3.7.1. Then gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analyses of core targets were carried out by DAVID to explore its possible molecular mechanism. The T2DM model was induced in rats by the high-fat diet combined with tail intravenous injection of streptozocin. The rats were divided into a normal group，a model group，a metformin group，and high-，medium- and low-dose AR-PLR groups. After four weeks of intragastric administration，the serum levels of fasting blood sugar （FBS），fasting insulin（FINS），aspartate aminotransferase（AST），alanine aminotransferase（ALT），triglyceride（TG），total cholesterol（TC），low-density lipoprotein cholesterin（LDL-C），high-density lipoprotein cholesterin （HDL-C），interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） of rats in each group were measured. The protein expression of insulin receptor substrate-2（IRS-2），phosphatidylinositol 3-kinase（PI3K），protein kinase B（Akt）， and forkhead box transcription factor O1（FoxO1） in rat liver was detected by Western blot. ResultA total of 131 core targets of AR-PLR in the treatment of T2DM were screened out by network pharmacology， where Akt1，mitogen-activated protein kinase 1 （MAPK1），TNF-α，and IL-6 were critical. As revealed by KEGG enrichment analysis， AR-PLR exerted the hypoglycemic effect mainly through the PI3K/Akt，TNF， and FoxO signaling pathways. Compared with the model group，the high- and medium-dose AR-PLR groups showed reduced FBS and FINS levels and increased glycogen level （P<0.05，P<0.01），all the AR-PLR groups showed decreased levels of AST，ALT，TG， and LDL-C （P<0.05，P<0.01）， the high- and low-dose AR-PLR groups showed decreased TC levels （P<0.05）. Compared with the model group， the high- and medium-dose AR-PLR groups showed reduced levels of IL-6 and TNF-α（P<0.05，P<0.01）， and the high-dose AR-PLR group showed increased expression of IRS-2， Akt， p-Akt， PI3K， and p-PI3K， and decreased expression of FoxO1 protein（P<0.05）. ConclusionAR-PLR has the characteristics of multi-component，Multi-target and multi-pathway in the treatment of T2DM. This herbal pair may regulate the PI3K/Akt/FoxO1 signaling pathway through IL-6， TNF-α， and other targets to affect insulin resistance， glycogen synthesis， gluconeogenesis， glucose transport， inflammation， immune response， and other processes， thereby treating T2DM.
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ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.
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Objective To identify related factors for hypoglycemic episodes in patients with type 2 diabetes mellitus(T2DM)through continuous glucose monitoring(CGM). Methods The included 147 patients with T2DM were those who had undergone CGM for 5 days in our ward of Department of Endocrinology and Metabolism,Huashan Hospital from Dec 2018 to Oct 2019. The general information, laboratory parameters and CGM parameters of the patients were collected. According to whether there wasan episode of hypoglycemia during the monitoring period,the patients were divided into non-hypoglycemia group and hypoglycemic group. A single hypoglycemia episode was defined as a sensor monitoring blood glucose of less than 3.9 mmol/L and lasting for more than 15 minutes.CGM parameters included the mean blood glucose(MBG),standard deviation(SD),coefficient of variation(CV),the differences between maximum and minimum blood glucose (BG) levels (ΔBG),mean amplitude of glycemic excursions (MAGE)and the percentage of time in range(％TIR)of BG at <3.9 mmol/L,3.9-7.8 mmol/L,>7.8 mmol/L,3.9-10.0 mmol/L,and >10.0 mmol/L. Results Logistic regression analysis showed that lower estimated glomerular filtration rate(eGFR)levels,increased use of insulin and its analogs and lower MBG levels were associated with hypoglycemic episodes. Spearman correlation analysis showed that the MBG level and the ％TIR of BG>7.8 mmol/L and BG>10.0 mmol/L were negatively associated while glycemic variability(GV)levels(SD,CV,ΔBG,MAGE)and ％ TIR of BG at 3.9-7.8 mmol/L were positively associated with hypoglycemic episodes. Pearson correlation analysis showed that the duration of hypoglycemic episodes was positively correlated with the use of sulfonylureas and CV levels. Conclusion Lower eGFR levels,increased treatment with insulin and its analogs and lower MBG levels were related factors for hypoglycemic episodes in patients with T2DM.
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Objective:To investigate the effect of compatibility of Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex couplet medicines on glucolipid metabolism in type 2 diabetic rats before and after salt-processing. Method:The type 2 diabetic rat model was induced by high-fat and high-glucose diet combined with low dose streptozotocin （STZ）， the model rats were randomly divided into six groups， including the model group， metformin group （200 mg·kg<sup>-1</sup>）， and different compatibility groups of raw and salt-processed of Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex （6.48 g·kg<sup>-1</sup>）. In addition， The same week old rats fed with normal diet were set as the blank group. After 30 d of continuous intragastric administration， changes of fasting blood glucose （FBG）， fasting serum insulin （FINS）， glycosylated serum protein （GSP）， hepatic glycogen， blood lipid ［total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）］， nonesterified fatty acid （NEFA）， adipocytokines ［adiponectin （ADP） and leptin）］， kidney function ［blood urea nitrogen （BUN） and creatinine （CRE）］ and other indicators of rats from different groups were detected， and the insulin sensitivity index （ISI） and insulin resistance index （HOMA-IR） were calculated， hematoxylin-eosin （HE） staining was used to observe the morphological changes of pancreas， liver and kidney of rats from different groups. Result:Compared with the model group， compatibility of Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex couplet medicines before and after salt-processing all could decrease the levels of FBG， GSP， TC， TG， LDL-C， NEFA， leptin， BUN， CRE and HOMA-IR， and increase the contents of FINS， HDL-C， ADP， hepatic glycogen and ISI， among which the compatibility of salt-processed Anemarrhenae Rhizoma and salt-processed Phellodendri Chinensis Cortex had the most significant effect on regulating glucolipid metabolism in type 2 diabetic rats. The compatibility of all couplet medicines could improve the histopathological changes of pancreas， liver and kidney in type 2 diabetic rats， among which the compatibility of salt-processed Anemarrhenae Rhizoma and salt-processed Phellodendri Chinensis Cortex had the most prominent effect on repairing pathological damage. Conclusion:The compatibility of Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex before and after salt-processing can improve glucolipid metabolism in type 2 diabetic rats， while the comprehensive effect of salt-processed Anemarrhenae Rhizoma and salt-processed Phellodendri Chinensis Cortex<italic> </italic>on lowering glucose and regulating lipid is the best.
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Objective:To explore the long-term effect of Zhenzhu Tiaozhi capsule（FTZ） on hemoglobin A1c（HbA1c）in patients with type 2 diabetes mellitus （T2DM） based on real-world data. Method:T2DM patients who were provided with FTZ （FTZ group） and those receiving conventional hypoglycemic drugs （control group） were extracted from the hospital information system （HIS） of the First Affiliated Hospital of Guangdong Pharmaceutical University， followed by propensity score matching （PSM） for balancing the confounding factors between groups. With HbA1c as the efficacy evaluation index， the difference in efficacy between the two groups was compared using <italic>t</italic>-test and <italic>χ</italic><sup>2</sup> test. For repeated measurement data of the same patient， the difference in efficacy and the stability of FTZ against HbA1c were analyzed by generalized estimating equation （GEE）. The factors that might affect the efficacy of FTZ against HbA1c were subjected to multivariate linear regression analysis （MLRA）， and the subgroup analyses were then conducted after the stratification of relevant factors. Result:There were 46 patients included in the FTZ group and 1 208 patients in the control group. PSM yielded 42 pairs of samples with balanced covariates between groups. As revealed by one-year observation， ① HbA1c in the FTZ group after treatment was 6.51%±1.09%. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. At the same time， the HbA1c compliance rate in the FTZ group was 73.8% after treatment. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. ② The GEE results showed that the post-treatment HbA1c levels in the two groups were not significantly different from each other. Moreover， the HbA1c level remained stable over treatment time. ③ MLRA and subgroup analyses results demonstrated that FTZ was more effective in patients with high baseline HbA1c ［<italic>β</italic>=-0.530，95% confidence interval（CI） -0.850～-0.209，<italic>P</italic><0.01］ or those who were complicated with hypertension （<italic>β</italic>=-0.918，95%CI -1.614～-0.222，<italic>P</italic><0.05）. Conclusion:In the real world， FTZ is able to control the blood sugar， and its effect is similar to those of conventional hypoglycemic drugs. Besides， it is capable of stabilizing the blood sugar for a long time.
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Objective:To investigate the action mechanism of Yinchenhao Tang against type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） in MKR mice. Method:Forty eight-week-old MKR mice were fed a high-fat diet for eight weeks and then divided into the model group，original Yinchenhao Tang （17.16 g·kg<sup>-1</sup>） group，Yinchenhao Tang group at a specified dose （4.68 g·kg<sup>-1</sup>） in teaching materials，and positive drug ［metformin + simvastatin， （65+2.6）×10<sup>-3</sup> g·kg<sup>-1</sup>］ group. Another 10 MKR mice of the same age were classified into the blank group and 10 FVB mice into the normal group. After eight weeks of intragastric administration in each group，the liver wet weight，oral glucose tolerance test （OGTT），serum inflammatory factors interleukin-6 （IL-6） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>），and changes in blood lipid and liver function were determined. Hematoxylin-eosin （HE） staining was conducted for observing the morphological changes in liver tissue under a transmission electron microscope，followed by the detection of Toll-like receptor 4 （TLR4），myeloid differentiation factor 88 （MyD88），and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） protein expression by Western blot. Result:Compared with the model group，the medication groups exhibited significantly reduced liver wet weight index （<italic>P</italic><0.01），improved OGTT result （<italic>P</italic><0.05），and down-regulated serum IL-6 and TNF-<italic>α</italic> levels （<italic>P</italic><0.01）. In terms of morphological changes，Yinchenhao Tang protected the hepatocyte structure and alleviated hepatocyte steatosis. Moreover， Yinchenhao Tang obviously down-regulated the protein expression levels of TLR4，MyD88，and NF-<italic>κ</italic>B in liver tissue of MKR mice with T2DM combined with NAFLD （<italic>P</italic><0.05），and the down-regulation of TLR4 and NF-<italic>κ</italic>B in the original Yinchenhao Tang group was better than that in the Yinchenhao Tang group at a specified dose in teaching materials （<italic>P</italic><0.05）. Conclusion:Yinchenhao Tang is able to reduce inflammatory factor levels and down-regulate TLR4，MyD88，and NF-<italic>κ</italic>B expression in liver tissue to relieve the pathological liver injury and interfere with T2DM combined with NAFLD of MKR mice. It exerts a certain liver-protective effect by lowering the blood lipids and delaying the hepatic inflammation.
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@#Introduction: Diabetic knowledge is one of the limiting factors in optimizing treatment for diabetic patients. Despite educational programs carried out by healthcare practitioners, most diabetic patients are not managing their diabetes well. Thus, this study aimed to determine the level of patients’ diabetic knowledge in Hospital Pakar Sultanah Fatimah and factors affecting it. Methods: A cross-sectional study was conducted among Type 2 Diabetic Mellitus (T2DM) patients in Hospital Pakar Sultanah Fatimah using the 14-item Michigan Diabetes Knowledge Test (MDKT) validated questionnaire. The questionnaires were self-administered by patients during their scheduled appointments at outpatient pharmacy and Medical Outpatient Clinic (MOPC). Descriptive statistics were used to summarize patients’ demographics, socioeconomic status and knowledge scores; while non-parametric tests were used to analyze the relationship between diabetic knowledge with patient demography and socioeconomic status. Results: There were a total of 262 respondents with median (IQR) age of 59(13.5) years. Majority of the patients were Malay, retiree/ unemployed and have household income less than RM3000. 66.4% of patients scored ≥7 points in MDKT-14. Race, household income and educational levels were significantly associated with knowledge scores (p=0.003, p=0.027 and p<0.001 respectively). A multivariate analysis was conducted and found that race and education level were significantly predictive of knowledge score with adjusted R2 =0.28. Conclusion: The respondents’ diabetic knowledge was moderate. By identifying the income, race and educational level as the contributing factors of patient’s poor diabetic knowledge score, we may target these areas to improve patients’ medication adherence and hence treatment outcome.
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OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.
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Humans , Receptors, Dopamine D1/genetics , MicroRNAs/genetics , Diabetes Mellitus, Type 2/genetics , Essential Hypertension/genetics , Biomarkers , Polymorphism, Single NucleotideABSTRACT
Objective: To analyze the medication rules of traditional Chinese medicine (TCM) in treating type 2 diabetes mellitus (T2DM),and explore the mechanism of action.Method: The articlesabout TCM treatment for T2DM in CNKI and Wanfang Med Online were retrieved.The data was entered into Excel 2013 to set up a database,and the factor analysis,association rules and cluster analysis were used to analyze core medication combinations by SPSS Statistics 19.0 and SPSS Modeler 14.1.kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using BATMAN-TCM to reveal the mechanism of action.Result: A total of 92 prescriptions were included,the high frequency medicines were Astragali Radix.The major properties of TCM were cold and plain.The major flavors of TCM were sweet and bitter.The major meridian tropism of TCM was livermeridian.These high frequency medicines were deficiency-nourishing herbs,and blood circulation-invigorating and stasis-eliminating herbs.Totally 6 core medication combinations were mined through association rules.Seven common factors were extracted from factor analysis.Clustering analysis was used to get 6 kinds of herbs.KEGG pathway analysis revealed 24 biological pathways and 6 diseases relating to T2DM.Conclusion: The most commonly used Astragali Radix for treating T2DM.In clinical,it can be combined with Poria,Salviae Miltiorrhizae Radix et Rhizoma and Rehmanniae Radix for treating T2DM.At the same time,it can be combined with such herbs as deficiency-nourishing herbs,and blood circulation-invigorating and stasis-eliminating herbs.The mechanism of action of high-frequency herbs may be related to the targets of exophosphatase/phosphodiesterase (PDEs),adenosine A1 receptor gene 1(ADORA1),adenosine A2A receptor gene (ADORA2A),neuropetide second receptor (NPY2R),and endothelial carbon monoxide synthase (NOS3) by interfering with PI3K/Akt,starch and sucrose metabolism signaling pathways.
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Objective: To observe effect of Mori Folium-containing serum on glucose consumption and cell activity of fat cell line 3T3-L1 insulin resistance (IR) model, in order to screen out the optimal concentration of drug-containing serum, detect effect of Mori Folium on the content of inflammatory factors, and explore the possible mechanism. Method: 3T3-L1 preadipocytes in logarithmic growth phase were selected, and induced with 10 mg·L-1 insulin (Ins), 0.25 mmol·L-1 dexamethasone (DEX) and 0.5 mmol·L-1 3-isobutyl-methylxanthine(IBMX) for 48 h and then with 10 mg·L-1 Ins for 48 h. After the cells were differentiated into mature adipocytes, they were induced with 1 μmol·L-1 DEX for 96 h to establish IR model. Glucose content in the supernatant of cells was detected by glucose oxidase after serum containing Mori Folium cultured for 12,24,36, 72 h. Methyl-thiazdyl-tetrazolium(MTT) was used to detect the effect of serum containing Mori Folium on IR cells activity. The content of tumor necrosis factor-α(TNF-α) was determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the effects of inflammatory factors on the expressions of insulin signaling pathway proteins insulin receptor (InsR), insulin receptor substrate (IRS), p-IRS1 and glucose transporter 4 (GLUT4) were determined by Western blot. Result: Serum containing Mori Folium could significantly increase the glucose consumption rate and cell activity of IR cells (Pα (PPPConclusion: Mori Folium can significantly improve IR status of 3T3-L1 cells, and its mechanism may be related to inhibiting TNF-α and promoting the expressions of insulin signaling pathway proteins.
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OBJECTIVE: To evaluate the effects of jejunal-ileal bypass(JIB) in addition to sleeve gastrectomy(SG) on glycemic regulation and body weight in Zucker Diabetic Fatty(ZDF) rats and underlying mechnisms. METHODS: Twelve ZDF(fa/fa) rats were randomly divided into two groups based upon the procedure performed including sleeve gastrectomy plus jejunal-ileal bypass surgery group(SG+JIB,n=6) and sleeve gastrectomy plus sham procedure group(SG+Sham,n=6). In addition,five healthy ZDF(fa/+) rats were employed as normal controls. Body weight,fasting blood glucose,food intake,oral glucose tolerance test and plasma GLP-1 levels were measured before surgery and at 2 and 4 weeks after surgery. RESULTS: Preoperatively,all baseline parametes had no statistical difference between SG+JIB and SG+Sham groups. In comparison with SG+Sham group,fasting plasma glucose levels at postoperative week 2(17.3 mmol/L vs. 8.7 mmol/L) and 4(21.4 mmol/L vs. 11.9 mmol/L)were significantly lower in SG + JIB group(P<0.0001). Oral glucose tolerace was significantly improved,represented by glucose excursion area under curve for 180 minutes period(4221 vs.2964,P<0.0001 at postoperative week 2;and 4104 vs. 3388,P<0.01 at postoperative week 4). Simutaneously,plasma GLP-1 levels were significantly higher in SG + JIB group than SG + Sham group(64.58 pmol/L v.s.30.52 pmol/L,P<0.001). However,SG + JIB had less food intake and body weight only decreased at postoperative week 2,but not at week 4. CONCLUSION: By adding JIB onto SG,the metabolic regulation capability is able to be furtherly enhanced. However,it seems that there is not additional benefit in weight loss.Therefore,based upon these results,we suggest that SG + JIB should be recommended to the patients who needs additional metabolic effects,but not to the patients for the purpose of additional weight loss above SG alone.
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Objective: To investigate the effect of Lycium barbarum polysaccharides on inflammatory cytokines in type 2 diabetes mellitus (T2DM) mice without myeloid differentiation factor 88 gene (MyD88-/-). Methods: Levels of interleukin 1β (IL-1β), IL-6, IL-8, transforming growth factor β1 (TGF-β1), and IL-10 in serum were assessed by ELISA in the MyD88-/- T2DM mice which had been administered with different doses of LBP (20, 40, and 80 mg/kg). Mouse macrophages Raw264.7 were stimulated by lipopolysaccharide (LPS) after treatment with different concentrations of LBP (25, 50, and 100 μg/mL). Then Western blotting was used to detect nuclear translocation level of nuclear factor κB (NF-κB) and protein expressions of inhibitor of NF-κB (IκB) and p-IκB. Results: Serum levels of IL-1β and TGF-β1 in MyD88-/- T2DM mice were down-regulated by LBP (P<0.05). Cell experiment proved that nuclear migration of NF-κB was dose-dependently inhibited by LBP, and the level of p-IκB was reduced by high dose of LBP. Conclusion: LBP can reduce some proinflammatory cytokines in the MyD88-/- T2DM mice, which may be related with its inhibitive effect on the phosphorylation of IκB and nuclear migration of NF-κB in the macrophages.
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Objective • To analyze the related risk factors of decreased heart rate variability (HRV) in type 2 diabetes mellitus (T2DM) patients. Methods • A total of 210 cases with T2DM in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from Jan. 2013 to Dec. 2014 were divided into two groups by the levels of urinary albumin creatinine ratio (UACR) and serum triacylglycerol (TAG), and with/without hypertension, respectively. By comparing the differences of clinical characteristics, HRV parameters and other general clinical data between the two groups, the correlations between HRV indexes and their risk factors were explored. Results • The average heart rate of the whole day was higher, and SDNN [normal RR intervals of sinus beats (NN intervals) standard deviation] was lower in the high UACR group than those in the normal UACR group (both P<0.05). The average heart rate of the whole day was higher, while SDNN and pNN50 (percentage of total heart beats with adjacent NN intervals greater than 50 ms) were lower in the hypertriglyceridemia group than those in the normal TAG group (all P<0.05). Minimum frequency domain power hour was lower in the hypertension group than that in the normotension group (P<0.05). Regression analysis showed that the linear correlativity between TAG and SDNN was very prominent (P<0.05), as well as between the diastolic blood pressure (DBP) and the average heart rate of the whole day, SDNN, frequency domain power 24 hours and minimum frequency domain power hour (all P<0.05). Similarly, the age was linearly correlated significantly with the average heart rate of the whole day, SDNN, SDANN (the standard deviation of the mean NN intervals every 5 min), frequency domain power 24 hours, minimum frequency domain power hour and maximum frequency domain power hour (all P<0.05). Conclusion • Age, TAG level and hypertension are the risk factors of decreased HRV in T2DM patients. Thus, early detection of the decrease of HRV in these patients can prevent the cardiovascular events of T2DM.
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Objective: To explore the risk factors associated with short-term progression of albuminuria in the patients with type 2 diabetes mellitus (T2DM). Methods: The retrospective cohort study design was performed to consecutively recruit 210 hospitalized T2DM patients who met the inclusion criteria, including 102 males and 108 females from April 2010 to April 2015. The data of the patients twice in hospital (as baseline and follow-up information, respectively), including general data, biochemical examinations and medication were collected. Multivariate Logistic analysis was used to explore the potential risk factors for baseline albuminuria and short-term progression of albuminuria. Results: Serum uric acid levels were significantly higher in the patients with macroalbuminuria ( ≥ 300 mg/24 h) than those in the patients without albuminuria (< 30 mg/24 h) at baseline (P=0.002). Among the 207 patients (excluding 3 samples with missing data) during the second hospitalization, 51 patients (24.6%) had progress in albuminuria and 156 patients (75.4%) had none. Serum uric acid levels were significantly higher in the progression group than those in the non-progression group (P=0.009). Multivariate Logistic regression analysis showed that high serum uric acid level was an independent risk factor for progression of albuminuria in T2DM patients (OR=1.349, 95%CI 1.014-1.793, P=0.040). Conclusion: The high serum uric acid level may be an independent risk factor for short-term progression of albuminuria, and early intervention with hyperuricemia might delay the progression of diabetic kidney disease in T2DM patients.
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@#Introduction: The prevalence of diabetes mellitus (DM) in Malaysia is drastically increasing. Subjects with DM are more likely to have deranged liver function tests (LFT). This study aimed to determine the prevalence of abnormal liver enzymes [(alanine aminotransferase (ALT) and alkaline phosphatase (ALP)] and its associated factors among type 2 DM (T2DM) subjects visiting a referral diabetic clinic in a tertiary government hospital. Methods: This retrospective, cross-sectional study included electronic data of 300 T2DM subjects ≥18 years old in the outpatient specialist clinic from January 2011 to December 2014. Statistical analysis was performed using SPSS version 22. Results: The study population at large included Malays, of age >60 years with comparable gender percentage. Most subjects had long-standing DM, poor glycaemic control and were on treatment. The prevalence of abnormal ALT and ALP was 27.3% and 13%; with 90.2% and 97.4% having mild ALT and ALP elevations, respectively. Significant associations noted for age, body mass index (BMI) and duration of T2DM for ALT whereas for ALP, anti-diabetic medication was significant between groups of normal and abnormal levels. Deranged liver enzymes were associated significantly with dyslipidaemia. Conclusion: Our study on the crude prevalence of raised liver enzymes may help identify T2DM patients at increased risk of non-alcoholic fatty liver disease (NAFLD). Modification of metabolic risk factors, such as weight loss, control of dyslipidaemia rather than just tighter glycaemic control should be emphasised to reduce morbidity and mortality. Liver enzymes remain a simple and non- invasive marker of liver pathology in daily medical practice