Effect of Zuoguiwan on Pancreatic Islet Function in Offspring of Maternal Rats with GDM / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Zuoguiwan on pancreatic islet function in offspring of gestational diabetes mellitus （GDM） maternal rat model and explore the mechanisms of Zuoguiwan in improving pancreatic islet function based on postpartum pancreatic regeneration. MethodHealthy female SD rats with normal blood glucose levels were paired with male rats in a 2∶1 ratio and housed together. Pregnancy was confirmed based on vaginal plugs or vaginal smears. The pregnant rats were divided into the following groups： normal group， model group， insulin group （insulin Detemir， 20 U·kg-1）， low-dose Zuoguiwan group （1.89 g·kg-1）， and high-dose Zuoguiwan group （3.78 g·kg-1）. The GDM rat model was induced using streptozotocin in rats except for those in the normal group. The model was confirmed by blood glucose testing in the maternal rats. Except for the normal and model groups， the other groups received daily administration of corresponding treatments. At 21 days after birth， fasting blood glucose （FBG） and fasting serum insulin （FINS） levels were measured in 6 offspring from each group. The homeostasis model assessment of insulin resistance （HOMA-IR） was calculated， and an oral glucose tolerance test （OGTT） was performed on additional 12 offspring from each group. Blood samples were taken from the abdominal aorta of the offspring at postnatal day 22， and enzyme-linked immunosorbent assay （ELISA） was used to measure insulin， glucagon （GC）， pancreatic polypeptide （PPY）， and somatostatin （SS） levels in the serum. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the pancreatic tissue of the offspring. Immunofluorescence （IF） was used to observe the area and structure of the pancreatic islets. Western blot was used to detect the expression of key proteins involved in the development and functional expression of pancreatic β-cells， namely pancreatic and duodenal homeobox factor 1 （Pdx1）， Nkx6.1， and Glucose transporter 2 （Glut2）. ResultCompared with the normal group， the model group showed significant increases in FBG and FINS levels， and HOMA-IR （P<0.01）. Compared with the model group， the insulin group showed significant decreases in FBG levels and HOMA-IR （P<0.01）， the low-dose Zuoguiwan group showed a significant decrease in FBG levels （P<0.05）， and the high-dose Zuoguiwan group showed significant decreases in FBG and FINS levels， and HOMA-IR （P<0.01）. Compared with the normal group， the model group showed significant increases in OGTT 60-min blood glucose levels and AUC index （P<0.05， P<0.01）. Compared with the model group， the high-dose Zuoguiwan group showed significant decreases in OGTT60-min blood glucose levels and area under the curve（AUC） index （P<0.05， P<0.01）. HE staining of pancreatic tissue showed that compared with the normal group， the model group had a reduced number of islets and a loose arrangement of acinar cells. Compared with the model group， the groups with drug treatment showed increased number of islets and a compact arrangement of acinar cells. Compared with the normal group， the model group had significantly increased levels of insulin， GC， PPY， and SS in the serum （P<0.01）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups and the insulin group showed significantly decreased serum levels of insulin， GC， PPY， and SS （P<0.05， P<0.01）. IF results showed that compared with the normal group， the model group had a significantly lower positive rate of insulin （P<0.05）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups showed a significant increase in the positive rate of insulin （P<0.05）. There was no significant difference in the positive rate of GC among the groups. In terms of the proportion of insulin and GC in individual islets， compared with the normal group， the model group showed a significant decrease in the proportion of insulin （P<0.01） and a significant increase in the proportion of GC （P<0.01）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups showed significantly increased proportion of insulin （P<0.01） and significantly decreased proportion of GC （P<0.01）. Compared with the normal group， the model group showed significantly decreased expression levels of Pdx1， Nkx6.1， and Glut2 proteins in the pancreatic tissue of GDM offspring （P<0.05）. Compared with the model group， the insulin group and the low-dose Zuoguiwan group showed significant increases in the expression levels of Pdx1 and Nkx6.1 proteins in the pancreatic tissue of GDM offspring （P<0.05）， and the low-dose and high-dose Zuoguiwan groups showed significant increases in the expression levels of Glut2 protein （P<0.05）. ConclusionZuoguiwan can promote pancreatic islet development in offspring of GDM maternal rat model， improve pancreatic islet morphology and function， and alleviate insulin resistance. Its mechanism of action may be related to the regulation of Pdx1， Nkx6.1， and Glut2 protein expression in the pancreatic tissue of offspring.

Effect of modified Xiaoke Prescription on the patients with Yin deficiency and heat excessive type 2 diabetes mellitus / 国际中医中药杂志

Objective:The purpose of this study was to explore the therapeutic effect of modified Xiaoke prescription on patients with Yin deficiency and heat excessive type 2 diabetes mellitus (T2DM), and its influence on TCM syndrome scores, pancreatic islet function and oxidative stress.Methods:Randomized controlled trial. Eighty patients with Yin deficiency and heat excessive T2DM treated in the hospital between January and July 2021 were selected, and divided into observation group (41 cases) and control group (39 cases) by random number table method. Patients in the control group were treated with conventional western medicine, and patients in the observation group were treated with modified Xiaoke Prescription on the basis of the control group. Both groups were treated for 1 month. TCM syndrome scores were performed before and after treatment. Fasting plasma glucose (FPG) and 2 hPG were measured by glucose oxidase method. Serum HbA1c, malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and SOD activity were measured by ELISA. The levels of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) were detected by colorimetry.Results:The total effective rate of the observation group was 92.68% (38/41), and that of the control group was 76.92% (30/39). The difference between the two groups was statistically significant ( χ2=3.89, P=0.048). After treatment, the scores of tiredness and fatigue, thirst and appetite, overeating and hunger, redness of tongue and lack of saliva and total scores in the observation group were significantly lower than those in the control group ( t=4.46, 16.89, 13.37, 8.58, 8.38, P<0.01). After treatment, the levels of serum FPG [(7.31±0.90) mmol/L vs. (8.72±1.50) mmol/L, t=5.13], 2 hPG [(9.64±2.05) mmol/L vs. (12.85±1.20) mmol/L, t=8.49], HbA1c [(7.64±0.58)% vs. (8.11±1.35)%, t=2.04] in the observation group were significantly lower than those in the control group ( P<0.05); MDA [(3.96±1.00) mmol/L vs. (5.04±0.73) mmol/L, t=5.49], 8-OHdG [(203.41±30.70) ng/L vs. (234.50±59.00) ng/L, t=2.98] levels were significantly lower than those in the control group ( P<0.05); The activity of serum SOD [(48.64±5.05) mU/L vs. (41.75±3.58) mU/L, t=7.01] was significantly higher than that of the control group ( P<0.01); The serum LDL-C [(2.01±0.11) mmol/L vs. (2.56±0.25) mmol/L, t=12.84], TC [(4.75±0.20) mmol/L vs. (5.12±0.07) mmol/L, t=10.93] levels were significantly lower than those in the control group ( P<0.01); The serum HDL-C [(1.62±0.18) mmol/L vs. (1.24±0.42) mmol/L, t=5.31] level was significantly higher than that of the control group ( P<0.01). Conclusion:The modified Xiaoke Prescription can improve clinical symptoms, curative effect and pancreatic function, and relieve oxidative stress on the patients with T2DM.

The impact of human umbilical cord-derived mesenchymal stem cells on the pancreatic function of type 2 diabetic mice and their regulatory role on NLRP3 inflammasomes / 中华内科杂志

Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

Effects of p,p'-DDE on H19 DMR methylation and insulin secretion of INS-1 cells / 环境与职业医学

Background Diabetes is a major threat to public health across the world. Studies have shown that exposure to p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) is closely related to the occurrence of type 2 diabetes mellitus. However, the relevant molecular mechanism is not clear. Objective To investigate the effects of p,p'-DDE on H19 differentially methylated region (DMR) methylation and insulin secretion of rat insulinoma cells (INS-1 cells). Methods INS-1 cells were cultured with different concentrations (0, 3.125, 6.25, 12.5, 25, 50, and 75 µmol·L−1) of p,p'-DDE for 24 h, and the viability of INS-1 cells was detected by CCK-8 method. INS-1 cells were exposed to 0, 12.5, 25, and 50 µmol·L−1 p,p'-DDE for 24 h in subsequent experiments. The methylation levels of 24 CpG sites in H19 DMR were analyzed by bisulfite genomic sequencing. The expression levels of insulin-like growth factor 2 (IGF2) mRNA were detected by real-time quantitative PCR. The expression levels of IGF2 and insulin-like growth factor-1 receptor (IGF1R) proteins were detected by Western blotting. The insulin secretion function of INS-1 cells was determined by glucose-stimulatedinsulin secretion test (5 and 25 mmol·L−1 glucose, respectively). Results Compared with the control group, the viability of INS-1 cells increased significantly after treatment with 12.5 µmol·L−1 p,p'-DDE; however, it was significantly inhibited after treatment with 50 or 75 µmol·L−1 p,p'-DDE (P<0.01); therefore, 50 µmol·L−1 was chosen as the maximum concentration of exposure for subsequent experiments. The 25 µmol·L−1 p,p'-DDE treatment decreased the methylation levels of CpG18 and CpG22-CpG24 sites in H19 DMR, and the 50 µmol·L−1 p,p'-DDE treatment decreased the methylation levels of CpG10-CpG24 sites (P<0.05 or P<0.05). Multiple concentrations (12.5, 25, and 50 µmol·L−1) of p,p'-DDE down-regulated the mRNA and protein relative expression levels of IGF2 and the protein relative expression levels of IGF1R. The transcription level of IGF2 decreased to 67.8%, 68.6%, and 62.5% of the control group, the protein level of IGF2 decreased to 73.3%, 79.5%, and 80.9% of the control group, and the protein level of IGF1R decreased to 54.8%, 25.6%, and 12.9% of the control group, respectively (P<0.01). In the high glucose context, p,p'-DDE at selected concentrations inhibited the insulin secretion levels to 85.0%, 58.6%, and 49.5% of the control group, respectively (P<0.01). Conclusion p,p'-DDE could down-regulate methylation level of H19 DMR, interfere the IGF2/IGF1R signaling pathway, and inhibit insulin secretion of islet cells.

Metformin combined with glucocorticoid in the treatment of SLE patients with IGT / 中国临床药理学与治疗学

AIM: To investigate the clinical curative effect of metformin combined with glucocorticoids in the treatment of patients with systemic lupus erythematosus (SLE) complicated with impaired glucose tolerance (IGT) and the effect on islet function and Th17/Treg cell imbalance. METHODS: Eighty-four patients with SLE complicated with IGT were randomly divided into the combined group and the control group with 42 cases in each group. All of them were given life and diet guidance. The control group was treated with glucocorticoids while the combined group was treated with metformin combined with glucocorticoids. One month later, the curative effect was observed, and islet function and Th17/Treg cell imbalance were evaluated. RESULTS: The total response rate of the combined group was significantly higher than that of the control group (90.48% vs. 71.43%, P0.05). CONCLUSION: Metformin combined with glucocorticoids is effective in the treatment of SLE with IGT. The treatment can control disease activity, lower blood glucose levels, improve islet function and correct Th17/Treg cell imbalance with high safety.

The differences in homeostasis model assessment values in type 2 diabetic patients with different lengths of history of diabetes

ABSTRACT Objective Type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic islet β-cell function over time and insulin resistance. Knowing more about the differences in pancreatic islet function in T2DM patients who have had diabetes for different lengths of time can help improve therapy for T2DM. Subjects and methods We conducted a cross-sectional study to compare islet β-cell function and insulin resistance in T2DM patients (n = 3,254) who had had diabetes for different lengths of time and those in normal controls (n = 794) using ANOVA and LSD analysis. Results We found that compared with that in normal controls, HOMA-β in T2DM patients with a history of diabetes of less than 1 year was lower (approximately 52% of that of normal controls, p = 0.003), while HOMA-IR in these patients was higher (approximately 50% of that of normal controls, p = 0.007). Compared with that in other diabetic patients, HOMA-β in patients with a history of diabetes of more than 30 years was the lowest. HOMA-IR in patients with a history of diabetes of between 20 and 30 years was lower than that in other diabetic patients (p < 0.05). Conclusions There were obvious decreases in HOMA-β and increases in HOMA-IR in T2DM patients with a history of diabetes of less than 1 year compared with those in normal controls. Therefore, early screening and intervention for T2DM might help improve islet function and delay the progression of diabetes.

Clinical Efficacy of Modified Bingtitang in Treatment of Type 2 Diabetes Mellitus and Effect on Pancreas Islet Function / 中国实验方剂学杂志

Objective:To investigate the clinical efficacy of modified Bingtitang in treatment of type 2 diabetes mellitus(T2DM) and its effect on pancreas islet function. Method:A total of 108 patients with T2DM were divided into two groups according to the digital number table method, with 54 cases in each group. The control group were given routine therapy of diabetic diet, proper exercise and blood sugar control, while the treatment group were orally given traditional Chinese medicine (TCM) and modified Bingtitang in addition to the therapy of the control group. The blood sugar, pancreas islet function-related indexes, TCM syndrome score, serum retinol binding protein 4 (RBP4) and Betatrohin levels were compared between two groups before and after treatment. The total effective rate was also compared. Result:After treatment, the fasting blood glucose (FPG), glycated hemoglobin (HbA1c), blood glucose variation coefficient (CV-FPG), insulin resistance index (HOMA-IR) of the treatment group were lower than those of control group (PΔI30/ΔG30)of treatment group were higher than those of the control group (PPPPConclusion:In addition to the routine treatment, modified Bingtitang can effectively control blood sugar, improve pancreas islet function, and alleviate TCM syndromes, with a significant effect on T2DM. Its mechanism may be related to the regulation of serum RBP4 and Betatrohin levels.

Correlation analysis of serum progesterone with clinical indicators and common traditional Chinese medicine syndrome types in male type 2 diabetic patients / 南方医科大学学报

OBJECTIVE@#To analyze the correlation of serum progesterone (PROG) level with blood biochemical parameters and common traditional Chinese medicine (TCM) syndromes in male patients with type 2 diabetes mellitus (T2DM).@*METHODS@#We collected the clinical data of 192 male patients with T2DM, who were admitted in the Department of Endocrinology, Nanjing Hospital of Chinese Medical Affiliated to Nanjing University of Chinese Medicine between January, 2018 and March, 2019. The general clinical data, C-peptide level, blood glucose level, glycated hemoglobin (HbA1c), HOMA, blood lipid level, and sex hormones were compared between the patients with normal PROG and elevated PROG levels and also between the patients with two common TCM syndromes, namely and deficiency syndrome and damp- heat accumulation in the spleen syndrome. We further compared the sex hormones, C-peptide level, HOMA, HbA1c, and blood glucose level among the patients with the two TCM syndromes having normal or elevated PROG levels.@*RESULTS@#Compared with those in patients with normal PROG level, BMI, C-peptide, HOMA-β, and HOMA2-IR were significantly lowered and HOMA-IS, E2, and T were significantly increased in patients with elevated PROG level; no statistical differences were found in age, disease duration, waist-to-hip ratio (WHR), smoking history, blood pressure, blood glucose, blood lipids, HbA1c, LH, FSH or PRL between the two groups. Compared with the patients with damp-heat accumulation syndrome group, the patients with and deficiency syndrome were older and had a longer disease duration, a greater BMI, and higher levels of PROG, C-Peptide, HOMA-β, HOMA2-IR and HOMA-IS, but the smoking history, WHR, HbA1c, blood glucose, and sex hormone levels were comparable between the two groups. Among the 4 groups of patients with different PROG levels and TCM syndromes, significant differences were found in the levels of C-peptide, HOMA-β, HOMA-IS, HOMA2-IR, PROG, E2, T, LH and FSH, and the patients with and deficiency syndrome as well as an elevated PROG level had the lowest C-peptide level, HOMA-β and HOMA2-IR and the highest HOMA-IS, PROG, E2, T, LH and FSH.@*CONCLUSIONS@#An elevated PROG level is closely related to islet cell dysfunction and TCM syndrome types in male patients with T2DM.

Effects of Glimepiride Combined with Metformin on Glucose and Lipid Metabolism, Islet Function and Serum miR-126 Expression of Newly Diagnosed Type 2 Diabetes Patients / 中国药房

OBJECTIVE: To investigate the effects of glimepiride combined with metformin on glucose and lipid metabolism, islet function and serum miR-126 expression of newly diagnosed type 2 diabetes patients. METHODS: A total of 100 patients with newly diagnosed type 2 diabetes in Nanchuan Hongren Hospital of Chongqing during Jan. 2014-Jan. 2017 were divided into observation group and control group according to random numble table, with 50 cases in each group. Control group was given Metformin hydrochloride sustained-release tablets (Ⅱ) with initial dose of 0. 5 g, once a day, adjusted to 0. 5 g 12 weeks later, twice a day, maximal dose of 1 g at meal or after meal. Observation group was additionally given Glimepiride tablets 2 mg, once a day, at breakfast, on the basis of control group. Both group were treated at lasted for 24 weeks. The levels of blood glucose (FPG, 2 hPG, HbA1c), blood lipid (TC, TG), islet function (FINS, 2 hINS, FCP, 2 hCP, HOMA-IR), serum miR-126 before and after treatment and the occurrence of ADR were observed in 2 groups. RESULTS: Before treatment, there was no statistical significance in the levels of blood glucose, blood lipid, islet function or serum miR-126 expression between 2 groups (P＞0. 05). After treatment, the levels of blood glucose, blood lipid and HOMA-IR in 2 groups were significantly lower than before treatment, and the levels of blood glucose and HOMA-IR in observation group were significantly lower than control group. The levels of FINS, 2 hINS, FCP and 2 hCP, serum miR-126 expression in 2 groups were significantly higher than before treatment, and the observation group was significantly higher than control group, with statistical significance(P＜0. 05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS: Glimepiride combined with metformin can significantly improve glucose and lipid metabolism, islet function, and regulate serum miR-126 expression without increasing the occurrence of ADR.

Research advances in functional regulation of islet α cells / 中华内分泌代谢杂志

Dysfuntion ofα cells plays a critical role in the pathogenesis of diabetes. Its own transcription factors, posttranscriptional modification, transporters related to secretion and paracrine signals fromβ and δ cells, inflammatory factors, and carbohydrates, lipids, amino acids, all influenceαcell function. We summaried the various factors involved in the regulation ofαcell function as well as recent related advances on their molecular mechanisms.

Study of isolation efficiency of new islet isolation solution for mouse islets / 器官移植

Objective To investigate the isolation and protective effect of a new islet purification solution (IPS)-Optiprep solution on the islet in mouse models. Methods The digested pancreatic islets were divided into the IPS and UW groups according to the islet volume. The pancreatic islets were isolated by the continuous gradient density centrifugation using IPS-Optiprep or UW-Optiprep solutions. The purification efficiency and isolated islet activity of purification solution were compared between two groups. The diabetic mouse models were successfully induced and randomly assigned into three groups. In the experimental group (n=10), the mice received pancreatic islet transplantation using islets isolated and purified by the IPS-Optiprep solution. In the control group (n=10), the mice underwent pancreatic islet transplantation using islets isolated and purified by the UW-Optiprep solution. In the sham surgery group (n=5), the mice merely underwent surgery without pancreatic islet transplantation. Postoperative blood glucose levels were detected and compared among three groups. The blood glucose levels of intraperitoneal glucose tolerance test at postoperative 21 d were statistically compared between the experimental and control groups. The cost of the preparation of two isolation solutions was also compared. Results Compared with the UW group, the islet equivalent (IEQ), islet purity, recovery rate and islet integrity were significantly higher in the IPS group. Islet morphological observation revealed that the islet membrane was complete and the islet diameter in the IPS group was considerably larger than that in the UW group. The activity of purified islets in the UW group was significantly higher than that in the IPS group [(88±5)% vs. (84±3)%, P<0.01]. Compared with the UW-Optiprep solution, identical in vivo islet function was obtained in the IPS-Optiprep solution.The cost of IPS-Optiprep solution was significantly less than that of the UW-Optiprep solution. Conclusions The new IPS-Optiprep solution yields higher islet isolation efficiency, purification, integrity and recovery rate and significantly reduces the purification cost compared with the UW-Optiprep solution. Nevertheless, IPS-Optiprep solution exerts a less protective effect on the activity of islet cells, which is probably correlated with the high islet integrity and the endotoxin in the IPS-Optiprep solution.

Clinical Observation of Insulin Glargine for Type 2 Diabetes Mellitus Patients with Poor Control by Rosigli-tazone and Metformin / 中国药房

OBJECTIVE:To observe the effects of insulin glargine in type 2 diabetes mellitus patients with poor glucose con-trol by rosiglitazone and metformin. METHODS:A total of 90 patients with type 2 diabetes mellitus with poor glucose control by rosiglitazone and metformin admitted to our hospital from Aug. 2013 to Dec. 2015 were divided into control group and observation group according to random number table,with 45 cases in each group. Control group was given Acarbose tablets 50 mg orally be-fore meal,tid,with maximal dose of 300 mg/d. Observation group was given Insulin glargine injection subcutaneously,qd,with initial dose of 0.15 u/kg,adjusted according to blood glucose monitoring,with maximal dose of 40 u/d. Both group were treated for 24 weeks. The levels of fasting blood glucose,2 h postprandial blood glucose,HbA1c,fasting C peptide and 2 h postprandial C peptide were compared between 2 groups before and after treatment. The time of blood glucose reaching target and the occur-rence of adverse events were recorded,and the incidence of adverse events was calculated. RESULTS:Before treatment,there was no statistical significance in above indexes between 2 groups(P>0.05). After treatment,The levels of fasting blood glucose and 2 h postprandial blood glucose in 2 groups were significantly lower than before treatment,and the levels of fasting C peptide,2 h postprandial C peptide and HbA1c were significantly higher than before treatment;except for fasting blood glucose,above indexes of observation group were significantly better than those of control group,with statistical significance (P<0.05). The time of blood glucose reaching target in observation group was significantly shorter than control group,the incidence of nocturnal hypogly-cemia,severe hypoglycemia,edema and gastrointestinal reactions and total adverse events in observation group were significantly lower than control group,with statistical significance(P<0.05). CONCLUSIONS:The application of insulin glargine in type 2 di-abetes mellitus patients with poor glucose control by rosiglitazone and metformin can effectively reduce the levels of blood glucose and HbA1c,and improve islet function with good safety.

Protective effects of combining human umbilical cord mesenchymal stem cells and glucagon like peptide-1 receptor agonist on the islet inflammatory injury in rat model of type 2 diabetes mellitus / 中华内分泌代谢杂志

T2DM+LIRA group and T2DM+LIRA+UC-MSCs group (P<0. 05). The ratio of insulin positive area in pancreas tissue was obviously rised, while the ratio of glucagon positive area in pancreas tissue was clearly descended in T2DM+LIRA+UC-MSCs group. And the same difference in valuating islet cells apoptosis by TUNEL could be observed ( P<0. 05). The expression of NF-κB and TLR4 protein in pancreas tissue of T2DM+LIRA+UC-MSCs group were the least amongthefourgroups[(0.75±0.10)vs(0.60±0.08),(0.47±0.08),(0.31±0.04),P<0.05]and[(1.24± 0. 12) vs (0. 93 ± 0. 10), (0. 95 ± 0. 09), (0. 74 ± 0. 07), P<0. 05 ]. Conclusion The combined treatment of liraglutide with umbilical cord mesenchymal stem cells is superior over a single treatment of liraglutide or umbilical cord mesenchymal stem cells in improving the islet function in type 2 diabetes mellitus models, which may be related to the down modulating the TLR4/NF-κB inflammatory signaling pathway.

Effects on pancreas islet function in patients undergoing laparoscopic myomectomy during sevoflurane and propofol anesthesia / 临床麻醉学杂志

Objective To investigate the effects on pancreas islet function in patients ubdergoing laparoscopic myomectomy during sevoflurane or propofol anesthesia.Methods Forty pa-tients,40-55 years,ASA Ⅰ or Ⅱ scheduled for elective surgery of laparoscopic myomectomy were randomly divided into two groups (n=20 each group).Propofol 2 mg/kg,sufentanil 0.5 μg/kg and rocuronium 0.9 mg/kg were used for induction,BIS was controlled between 40 and 55 during surgery.The anesthesia was maintained with sevoflurane and MAC was maintained with 0.7-1.3 in group S.The anesthesia was maintained with propofol continuous infusion and the plasma concentra-tion of target was set between 2.0 to 5.0μg/ml in group P.Blood glucose,insulin,c-peptide,gluca-gon and cortisol were measured at 3 time points:before induction of anesthesia (T0 ),start of surgery (T1 ),end of surgery(T2 ).Results Compared with T0 ,blood glucose,insulin,c-peptide,glucagon and cortisol in two groups were increased significantly at T1 and T2 (P <0.05).Compared with T1 , blood glucose,insulin,c-peptide,glucagon and cortisol in two groups were increased significantly at T2 (P <0.05).Compared with group S,blood glucose,glucagon and cortisol were increased indis-tinctively and insulin,c-peptide were increased significantly in group P at T1 and T2 (P < 0.05). Conclusion Compared with sevoflurane,propofol could promote the secretion of insulin and c-pep-tide,and inhibit cortisol and glucagon secretion,thus inhibit the rise of intraoperative blood glucose.

Effect of liraglutide combined with insulin on HbA1c, T lymphocyte subsets and islet function in patients with type 1 diabetes / 中国生化药物杂志

Objective To investigate the effect of liraglutide combined with insulin on the HbA1c, T lymphocyte subsets and islet function in patients with type 1 diabetes.Methods 46 cases from endocrinology department of Tangshan Traditional Chinese Medicine Hospital with type 1 diabetes were selected and randomly divided into two groups each group had 23 patients.Control group were given recombinant human insulin to control blood sugar according to the blood glucose level, and experimental group were given liraglutide on the basis of control group.HbA1c, T lymphocyte subsets, C-Peptide ( CP) and islet function were compared after treatment.ResuIts Compared with control group after treatment, HBAlc level in experimental group was lower (P<0.05); CD4 +T was higher, CD8 +T was lower, and CD4 +/CD8 +T was higher (P<0.05); the fasting plasma glucose (FPG) level was lower (P<0.05);2-hour postprandial blood glucose (2 hPG) was lower (P<0.05); CP and 2-hour postprandial C-Peptide (2 hCP) were higher (P<0.05).There was no significant difference in liver and kidney function between two groups.ConcIusion Liraglutide combined with insulin could significantly reduce serum glycated hemoglobin level, increase CD4 +T level and reduce CD8 +T level, improve islet function in patients with type 1 diabetic.

Effects of efaroxan on insulin release from pancreatic βcells / 中国药理学通报

Aim To study the insulinotropic effects of Efaroxan and the underlying mechanism in rat βcells. Methods Pancreatic islets were isolated by college-nase p digestion.Radioimmunoassay was used to meas-ure insulin secretion and cAMP level in rat pancreatic islets.Results Efaroxan only potentiated insulin se-cretion at high glucose concentrations(8.3,1 1 .1 mmol ·L -1 )but not at low glucose concentrations.KU1 4R,an antagonist of Efaroxan,remarkably inhibited Efarox-an-potentiated insulin secretion;and similarly,KU1 4R significantly inhibited forskolin-induced and IBMX-in-duced insulin secretion.cAMP measurement showed that forskolin and IBMX significantly increased cAMP levels,but Efaroxan and KU1 4R had no effects on cAMP content in pancreatic islets.Conclusion The mechanism of Efaroxan-potentiated insulin secretion is related to downstream of cAMP signaling pathway, KU1 4R antagonized the downstream of cAMP signaling leading to its inhibitory effects on Efaroxan,forskolin and IBMX-induced insulin secretion.

Effect of pioglitazone on oxidative stress and islet function in rats suffered from chronic intermittent hypoxia / 中国药学杂志

OBJECTIVE: To investigate effects of pioglitazone on oxidative stress and islet function in rats suffered from chronic intermittent hypoxia. METHODS: A chronic-intermittent hypoxia model in rats was established. Forty-eight male SD rats were randomly assigned into three experimental groups (n=16/group), normoxia control group, chronic intermittent hypoxia model group, and pioglitazone intervention group. Rats in NC group were raised normally, while rats in CIH and pioglitazone group were exposed to alternative cycles of O2 and N2. Rats in pioglitazone group were fed with pioglitazone (10 mg·kg-1·d-1) by gavaged, and both the CIH and NC groups were treated with isovolume normal saline solution (NS). The rats were sacrificed at 4 and 8 weeks and changes were detected about tumor necrosis factora, malondialdehyde, glutathione peroxidase, 8-iso-prostaglan-din F2α, superoxide dismutase in serum as well as HOMA-β and the expression of nuclear transcription factor-κB mRNA in pancreas tissue. RESULTS: Compared with NC group, the level of TNF-α, MDA, 8-iso-PGF2α in serum and expression of NF-κB mRNA increase, GSH-Px, SOD and HOMA-α declines in CIH group (P0.05). Compared with CIH group, the level of TNF-α, MDA and 8-iso-PGF2a in serum and expression of NF-κB mRNA in pancreas tissue decline, GSH-Px, SOD and HOMA-β rises in pioglitazone rats (P<0.05 or P<0.01), and those detections in pioglitazone 8 group show more remarkable changes than rats in pioglitazone 4 group (P<0.05 or P<0.01). CONCLUSION: The condition of CIH results in oxidative stress and islet β cell dysfunction of rats. Pioglitazone can degrade oxidative stress level through inhibiting NF-κB translocation and improve islet β cell function in chronic intermittent hypoxia rats, dependent of time to some degree.

New progress in the protection of Traditional Chinese Medicine on islet function / 医学研究生学报

So far, the major therapeutic drugs of diabetes are western medicine , but side effects of hypoglycemic western med-icine are large and not easy to take for a long time .In recent years , we found the side effects of some kind of hypoglycemic Chinese herbal medicine were small , much easier to be accepted by the patients .Thus, the clinical treatment of diabetes may have new meth-ods.According to the mechanisms of Traditional Chinese Medicine for protection of islet function , this review will discuss them from re-ducing oxidative stress , increasing the number of islet cells and promoting βcells to secrete, relieving insulin resistance , increasing in-sulin sensitivity and so on .All of these aspects reflect the unique role of Traditional Chinese Medicine in the treatment of diabetes and protection of islet function .

Clinical Observation on Effect of Qinghua Granules on Glycometabolism, Pancreatic Islet Function and Oxidative Stress in Type-2 Diabetics with Heat Syndrome / 世界科学技术-中医药现代化

This study was aimed to evaluate effect of Qinghua Granules (QHG) on glycometabolism, pancreatic islet function and oxidative stress in type-2 diabetics with heat syndrome. A total of 60 cases of type-2 diabetics with heat syndrome (according to the Syndrome Element Syndrome Differentiation) were enrolled in the clinic of the Department of Endocrinology and Metabolism, Shuguang Hospital Affiliated to Shanghai University of Tradi-tional Chinese Medicine. The average age of enrolled cases was (57.9 ± 6.9) years. Enrolled cases were randomly divided into the treatment group and the control group. The original hypoglycemic plan was continued to use. In the treatment group, QHG was administrated. And in the control group, placebo was given. The administration dosage in both groups was one package per day. The treatment course was 12 weeks. The fasting and postpran-dial (120 min after standard meal) blood samples before and after medication were collected. The main evalua-tion indexes were fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and hemoglobin A1c (HbA1c). The secondary evaluation indexes were homeostasis model assessment (HOMA2-%B, HOMA2-%S, HOMA2%-IR), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), maleic dialdehyde (MDA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). The anal-ysis of variance was used in the comparison of efficacy between two groups . The results showed that HbA1c in the treatment group was obviously reduced, and HOMA2-%B was obviously increased. There was no significant changes in the control group ( P = 0 . 044 , P = 0 . 016 ) . In the treatment group , SOD increased obviously , MDA reduced obviously. There was no significant change in the control group. There was difference b etween two groups (P = 0.011, P = 0.049). There was no change on blood lipids or other evaluation indexes. It was conclud-ed that QHG is effective in the improvement of glycometabolism, islet β-cell functions and oxidative stress in type-2 diabetics with heat syndrome .

Protective effects of RGD peptides on islet viability and function / 中华内分泌外科杂志

Objective To investigate the effect of argenin-glycin-aspartic acid (RGD) peptides on islet viability and function. Methods Rats were randomly divided into 2 groups: 1640 group and RGD group. Ficoll was used to purify islet in a discontinuous-density-gradient way. Islet concentration is 27% ,25% ,23% ,20.5% and 11% respectively. Acridine orange/ethidium bromide(AO/EB) fluorescent staining method was adopted to observe the effect of RGD peptides on islet viability. Radioimmunoassay was adopted to detect insulin level and measure insulin secretion index (SI). Caspase-9 cells and phospho-Akt 473-positive cells were determined by flow cytometry to investigate the influence of RGD peptides on caspase-9 activity and Akt. Results 600-700 IEQ islet was extracted from each rat by Ficoll purification through modified gradient centrifugation. AO/EB stain showed islet survival rate was more than 95% immediately after separation. Islets cultured in the medium of RPMI-1640 showed SI of 1.64 ±0.28 after 1 week, while islets cultured in the medium of RPMI-1640 containing RGD peptides showed SI of 2.28 ± 0.16 (P ＜ 0.05 ). Flow cytometry showed the level of activated caspase-9 was ( 22.66 ± 3.56 ) % if islet was cultured in RPMI-1640 alone for 1 week while the level was( 10.54 ± 1.96) % if islet was cultured in RPMI-1640 containing RGD peptides. There was statistical difference ( P ＜ 0. 05 ). The effect of RGD on Akt phosphorylation was also detected. Akt phosphorylation proportion was (31.47 ±4.08)% 1 week after cultured in RPMI-1640 while the value was(61. 054 ±6.03)% if cultured in RPMI-1640 containing RGD peptides. The difference had statistical significance (P ＜ 0. 05). Conclusion RGD peptides could inhibit apoptosis through the phosphorylation of Akt/PKB.