Medicated effect of CDKN1B on promoting proliferation of islet β cells in diabetes mellitus / 中国综合临床

The serious decrease in the number of functional β cells is one of the main features in the pathogenesis of diabetes mellitus. CDKN1B is a new kind of regulatory protein, which can bind and inactivate cyclin and cyclin-dependent kinase complex to control the process of cell cycle. It was suggested that down-regulation or deletion of CDKN1B in islet β cells could accelerate the proliferation of islet β cells, thus increasing the number of islet β cells, which is of great significance for treatments of diabetes.

Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Asiatic acid improves insulin secretion of β cells in type 2 diabetes through TNF- α/Mfn2 pathway / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg－1·d－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.

Application of single cell RNA sequencing in the treatment of diabetes / 中华内分泌代谢杂志

Single-cell RNA sequencing (scRNA-seq) is used for transcriptome profiling at the individual cell level, which is capable of screening in differentially gene expression that results from genetic mutation. Islet-based developmental atlas and heterogeneity characterization are currently the main applications of scRNA-seq in diabetes. scRNA-seq also can be used to mark and purify the functional β cells from resident adult stem cells in the pancreatic islets, which is expected to improve the outcome of islet β cells transplantation in type 1 diabetic patients. In addition, the technique can aid in learning diabetic β cell dedifferentiation and immunomodulatory functions. Although the study of scRNA-seq in diabetic retinopathy, nephropathy, atherosclerosis, and peripheral neuropathy is still at a nascent stage, scRNA-seq has great potential in a wide range of biomedical and clinical applications.

Ketogenic diet improves pancreatic β-cell dedifferentiation in db/db mice / 中华内分泌代谢杂志

Objective:To evaluate the effects of ketogenic diet(KD) on pancreatic β-cell dedifferentiation in db/db mice.Methods:In animal study, 8-week-old db/db male mice with type 2 diabetes mellitus(T2DM) were randomly divided into 3 groups: T2DM model group(ND), KD group, 75% caloric restriction(CR) group, and male C57BL/6 mice of the same age as normal control group(C) fed with standard diet. Both C and ND groups were on ad lititum feeding of chow, the KD group was free to eat the ketogenic diet, and the CR group was the positive control group, consuming 75% of the calories of the ND group every day. Four weeks after different diet intervention, body weight, fasting blood glucose, fasting insulin, glucose tolerance and blood β-hydroxybutyric acid(BHB) were measured. Morphology and structure of pancreatic islet was observed by hematoxylin-eosin staining(HE). Immunofluorescence co-staining was used to observe the expression of mouse pancreatic β-cell specific transcription factors.Results:After 4 weeks diet intervention, the fasting blood glucose, insulin and the area under the curve of blood glucose in KD group was significantly decreased( P<0.05); When compared with ND group, the morphology and structure of the islets in the KD group were more regular, and the number of islet cells increased as revealed with HE staining. Pancreatic immunofluorescence co-assay showed that KD not only restored the number and arrangement of β-cells and the ratio of β/α-cell in the pancreatic islets, but also reversed the expression of specific β-cell transcription factors such as pancreatic duodenal homeobox factor-1(PDX1). Conclusion:KD can reduce fasting blood glucose, fasting insulin and improve glucose tolerance in db/db mice, which may be related to its ability to restore the expression of specific β-cell transcription factors and reverse the dedifferentiation of pancreatic β-cells.

TGF-β-related Signaling Pathways in Pathogenesis of Diabetes and Prospect of Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

The incidence of diabetes has been on the rise as the result of lifestyle changes， especially the high-fat diet and reduced exercise. Thus， it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β （TGF-β） signaling pathways with diabetes complications and tumors， but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors， directly or indirectly leading to the apoptosis of islet β cells and insulin resistance （IR）， and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase （AMPK）， protooncogene （c-Myc）， Ski-relatednovel protein N （SnoN）， Smad ubiquitination regulatory factor 1 （Smurf1）， miR-335-5p， and other signaling molecules. They participate in the occurrence and development of IR， apoptosis of islet β cells， insulin secretion disorder， fibrosis of adipocytes， and metabolic disorder of adipocytes， and inhibit the browning of white adipose tissue， playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine （TCM）， the pathogenesis of diabetes is the deficiency of Qi and Yin， and the late stage is characterized by the syndrome of Qi deficiency， and Yang deficiency and blood stasis， which should be treated according to the principle of replenishing Qi and nourishing Yin， warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways， elucidating the roles of them in pathogenesis of diabetes， and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

Effects of high-intensity interval training on glycemia and the pancreatic β-cell functioning of persons with type 2 diabetes / 中华物理医学与康复杂志

Objective:To explore any effect of 8 weeks of high-intensity interval training (HIIT) on glycemia and pancreatic β-cell function among persons with type 2 diabetes to provide data for optimizing their exercise protocol.Methods:Sixty patients with type 2 diabetes and without a habit of regular exercise were randomly divided into an exercise group ( n=30) and a control group ( n=30). Both groups maintained their daily living habits, except that the exercise group practiced HIIT on a power vehicle ergometer 3 times a week for 8 weeks. Before and after the intervention, the 2-hour oral glucose tolerance test (OGTT) was conducted to evaluate glycemia and pancreatic β-cell function. Body composition was also detected using dual-energy X-ray absorptiometry. Results:After the intervention a significant decrease was observed in the fasting blood glucose, mean blood glucose, glycosylated hemoglobin, blood glucose levels at the end of a 2h OGTT, blood glucose area under the curve and homeostatic model assessment of insulin resistance, as well as waist circumference and abdominal fat content of the exercise group. And there was a significant increase in the homeostatic model assessment of pancreatic β-cell function and disposition index among the exercise group. In the control group no significant differences were observed.Conclusion:Eight weeks of HIIT can improve glycemia and pancreatic β-cell function and reduce abdominal fat among persons with type 2 diabetes. It can be used as an effective rehabilitation protocol.

Effects of recombinant human syntaxin-4(STX4) on lipopolysaccharide-induced islet β-cell INS-1 injury and underlying mechanism / 中华内分泌代谢杂志

Objective:To explore the effect of recombinant human syntaxin-4(STX4) on lipopolysaccharide(LPS)-induced injury in islet β-cells(INS-1).Methods:Pancreatic islet β-cells(INS-1) were divided into Control (blank control), LPS (LPS treatment), LPS+ NC (transfection of negative control vector, LPS treatment), and LPS+ STX4 (transfection of pcDNA-STX4, LPS treatment) groups. RT-qPCR and Western blot were used to detect STX4 mRNA and protein expression, flow cytometry to detect apoptosis, DCFHDA method to detect reactive oxygen species(ROS) level, xanthine oxidation method to detect superoxide orgotein dismutase(SOD) level, colorimetric method to detect glutathione peroxidase(GSH-Px) level, ammonium molybdate colorimetric method to detect catalase(CAT) level, thiobarbituric acid method to detect malonaldehyde(MDA) level, ELISA method to detect the level of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and insulin secretion levels under glucose conditions secreted by cells, Western blot method to detect Cleared Caspase-3, Bcl-2 Associated X Protein(Bax), p65 protein expression. After treatment with NF-κB signaling pathway activator, STX4 up-regulated islet β-cell INS-1 was given LPS stimulation, and the same method was used to measure apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α, insulin levels and Cleaved Caspase-3, Bax, p65 protein levels.Results:Compared with the Control group, the expression of STX4 mRNA and protein in islet β cells of the LPS group decreased, the apoptosis rate, ROS level, and MDA levels increased, and the levels of SOD, GSH-Px, and CAT decreased, the levels of IL-1β, TNF-α increased, the level of insulin secreted by the cells decreased, and the expression levels of Cleaved Caspase-3, Bax, and p65 also increased. NF-κB pathway activator treatment reversed the effect of up-regulated STX4 on islet β-cell apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α levels, and Cleaved Caspase-3 , Bax and p65 protein levels.Conclusion:Up-regulation of STX4 alleviated LPS-induced islet β cell oxidative damage, apoptosis and inflammatory factor release. The underlying mechanism might be related to the inhibition of activated NF-κB signaling pathway.

Clinical Efficacy of Modified Huanglian Wendantang in Treatment of Newly Diagnosed Type 2 Diabetes Mellitus with Phlegm (Dampness)-Heat Syndrome / 中国实验方剂学杂志

Objective:To observe the efficacy of modified Huanglian Wendantang in treating newly diagnosed type 2 diabetes mellitus （T2DM） with phlegm （dampness）-heat syndrome， in order to study the effect on islet β cell function and adipocytokines. Method:A total of 130 patients were randomly divided into two groups by random number table （65 cases in each group）. The 60 patients in control group completed the treatment （4 patients fell off or lost visit， 2 were eliminated because of breach of plan）， and the 61 patients in observation group completed the treatment （3 patients fell off， 1 were eliminated）. And 20 healthy volunteers were taken as normal control group. Both groups′ patients got lifestyle interventions and metformin hydrochloride tablets （1 tablet/time， 1 time/day during the meal）. In addition， patients in control group got Huazhuo Qingshen Keli in the morning and at night， 5 g/time， 2 times/day， and patients in observation group got modified Huanglian Wendantang， 1 dose/day. And the treatment was lasted for 3 months. Before and after treatment， levels of fasting blood glucose （FBG）， postprandial 2 blood glucose （PBG）， HbA1c and fasting insulin （FINS）， insulin resistance index （HOMA-IR）， insulin sensitivity index （InISI）， islet β cell function index （HOMA-β）， early insulin secretion index （I30/△G30） and late insulin secretion index （AUCI30~I120/G30~G120）， total cholesterol （TC） and triglycerides （TG）， high-density lipoprotein （HDL-C）， low-density lipoprotein （LDL-C）， adiponectin， TNF -α （TNF-α）， resistin and leptin were detected. And syndrome of phlegm （dampness） combined with heat were scored， and the safety was discussed. Result:The total effective rate in observation group was 91.80% （56/61）， which was higher than 78.33% （47/60） in control group （χ2=4.333， P<0.05）. And the score of phlegm （dampness）-heat syndrome was lower than that in control group （P<0.01）， levels of FBG， PBG， HbA1c， HOMA-IR， AUCI30~I120/G30~G120， TC， TG， LDL-C， TNF-α， leptin and resistin were lower than those in control group （P<0.01）， while levels of I30/△G30， HOMA-β， InISI， HDL-C and adiponectin were higher than those in control group （P<0.01）. There was no adverse reaction related to modified Huanglian Wendantang. Conclusion:In addition to treatment with metformin， modified Huanglian Wendantang can effectively control blood glucose and lipid， regulate adipocyte factor， improve early and late phase insulin secretion， improve the function of β cell and insulin sensitivity of islet， improve IR， with a better comprehensive efficacy and a safety in clinical use.

Role of autophagy in IL1 ßinduced apoptosis of rat pancreatic INS1 islet β cells / 中国药理学通报

Aim To investigate the role of autophagy in IL1 ßinduced apoptosis of islet ß cells. Methods Rat ß cell line INS1 was cultured in vitro. The survival rate of INS1 cells was measured by CCK8 method at different concentrations and time. The level of apoptosis was analyzed by flow cytometry and Western blot, and the expressions of autophagyrelated proteins were detected by Western blot. Results ILlβ could reduce the survival rate of INS1 cells in a concentrationand timedependent manner (P < 0.05, P < 0. 01). Compared with control group, with the increase of IL1 β concentration, the level of apoptosis of INS1 cells increased gradually (P < 0. 05); at the same time, the expression of autophagy increased gradually (P < 0. 05). Pretreatment with autophagy agonist rapamycin (RAPA) could increase autophagy (P < 0. 05) and apoptotic level (P < 0. 05). However, the expression of autophagy and apoptosis decreased after pretreatment with autophagy inhibitor 3MA (P < 0 . 0 5) . Conclusion IL1 ß can promote the apoptosis of INS1 cells by inducing autophagy.

The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.

Progress of prolactin in regulating the function of pancreatic β cells / 中华内分泌代谢杂志

Prolactin is a polypeptide hormone that regulates cell growth and development. Recent studies have shown that prolactin is involved in the regulation of glucose metabolism and is closely related to blood glucose homeostasis. This paper is to review the research progress of prolactin in islet β cells, including the understanding of prolactin and its receptor, the associations of prolactin with glucose metabolism, and the proliferation, apoptosis and secretion of pancreatic beta cells.

Implication of proinsulin to insulin ratio in the basic and clinical research of diabetes / 中华内分泌代谢杂志

Proinsulin is the precursor of mature insulin.Proinsulin to insulin ratio reflects the degree of pancreatic β-cell dysfunction and the progression of type 2 diabetes, and may predict the risk of diabetes development.Some variants in susceptibility genes of diabetes are associated with the elevation of proinsulin to insulin ratio.Moreover, several antidiabetic drugs are able to decrease the proinsulin to insulin ratio in patients with type 2 diabetes.Therefore, the proinsulin to insulin ratio may act as a simple and useful indicator in the etiological study, risk prediction, disease progression and therapeutical evaluation in type 2 diabetes.

Function of lncRNA TUG1 in Insulin Secretion from Pancreatic Beta Cells / 现代生物医学进展

Objective:To determine the role of lncRNA TUG1 in pancreatic β cells functioning both in vitro and in vivo.Methods:The lncRNA TUG1 expression in mice pancreas,brain,muscle and other different tissues was examined through qRT-PCR.MTT,flow cytometry,GSIS,ELISA and immunochemistry analyses were performed to detect the effect of lncRNA TUG1 on insulin secretion in vitro and in vivo.Results:lncRNA TUG1 was highly expressed in pancreatic tissue compared with other organ tissues.Knockdown of lncRNA TUG1 expression resulted in decreased insulin secretion in β cells both in vitro and in vivo.Immunochemistry analyses showed decreased relative islet area after treatment with lncRNA TUG1 siRNA.Conclusions:Downregulation of lncRNA TUG1 expression can affect insulin secretion in pancreatic β cells in vitro and in vivo,and lncRNA TUG1 may represent a factor that regulates the function of pancreatic β cells.

Effect of aerobic exercise on pancreatic islets and explorationof their mechanism in type 2 diabetic rats / 中国比较医学杂志

Objective To explore the effect and mechanism of aerobic exercise on islet β-cells in type 2 diabetic rats.Methods Thirty healthy SPF 8-week old Wistar rats were randomly divided into control group (C, n=10), diabetic control groups (DMC) and diabetic exercise (DME) groups, 10 rats in each group, among which 7 successful rat models were used in the experiment.The diabetic rat model was established by high fat and sugar diet and i.p.injection of streptozotocin in a dose of 50 mg/kg.The rats of group DME were forced to perform 20 m/min running for 30 min, once a day, 6 days in a week, for 8 weeks.Other rats were allowed free movement.At the end of experiment, serum glucose and insulin were measured and homeostasis model assessment (HOMA) was calculated, and pancreatic tissue samples were collected for histopathological examination.The morphology and structure of pancreatic islets were observed under a digital microscope, the perimeter and area of islets were analyzed by image analysis, and shape factor of islets was calculated.The insulin content, glucokinase and ultramicro-ATPase activity in the pancreatic homogenate were determined.Results In the DME group, the perimeter and area of islets were significantly higher than the DMC group (P< 0.05), but still lower than the control group.The shape factor was significantly increased, the cell hypertrophy, vacuolization and nuclear pyknosis were markedly alleviated than those in the DMC group, the insulin content, glucokinase and the trace total ATP activity in the DME group were significantly higher than those in the DMC group (P<0.05), and the SF and HOMA were significantly changed.Conclusions Aerobic exercise can reduce the blood glucose level, improve the morphology of islets and β-cells in the type 2 diabetic rats.It may be due to increase of the activity of glucose kinase and ATP-synthase, and increased insulin sensitivity in the pancreas.

Relationships between islet β-cell function and infection,inflammation and major organ function in multiple organ dysfunction syndrome patients with severe traumatic hemorrhage / 重庆医学

Objective To analyse the relationships between islet β-cell function and infection,inflammation and major organ function in multiple organ dysfunction syndrome (MODS) patients with severe traumatic hemorrhage.Methods A total of 187 cases of MODS patients hospitalized in the 94th Hospital of PLA from January 2013 to January 2016 were selected,and were divided into the MODS survival group (MODS-S group,104 cases) and MODS dead group (MODS-D group).Other 100 healthy subjects were selected as the control group.The fasting blood glucose (GLU0) and insulin (INS0) levels,blood glucose (GLU30) and insulin (INS30) levels after 30 min of glucose loading,and levels of soluble triggering receptor expressedon myeloid cells-1 (sTREM-1),tumor necrosis factor-α (TNF-a),interleukin-6 (IL-6),alanine aminotransferase (ALT),creatinine (Cre) and creatine kinase isoenzyme (CK-MB) in different groups were determined.The insulin-β-cell function was evaluated by homeostasis model assessment of β-cell function (HOMA-β) index and ratio of insulin increment and blood glucose increment after 30 min of glucose loading (ΔINS30/ΔGLU30),and their relationships to other indexes,including sTREM-1,TNF-α,IL-6,GLU0,ALT,Cre and CK-MB,in MODS patients with severe traumatic hemorrhage were analysed.Results The HOMA-β and AINS30/AGLU30 ratio in the MODS-D group were lower than those in the MODS-S group,and levels of sTREM-1,TNF-α,IL-6,ALT,Cre and CK-MB in the MODS-D group were higher than those in the MODS-S group,there were statistically significant differences (P＜0.01).In MODS patients with severe traumatic hemorrhage,HOMA-β and ΔINS30/AGLU30 was both negatively correlated with sTREM-1,TNF-α,IL-6,GLU0,ALT,CreandCK-MB (r=-0.356 4,-0.532 1,-0.345 8,-0.772 1,-0.762 5,-0.684 8,-0.606 4;r=-0.428 5,-0.567 8,-0.487 0,-0.743 6,-0.781 7,-0.717 6,-0.640 1,P＜0.01).Conclusion MODS patients with severe traumatic hemorrhage have islet β-cell dysfunction which may be used as a prognostic and diagnostic indicator.

Relationships between islet β-cell function and infection,inflammation and major organ function in multiple organ dysfunction syndrome patients with severe traumatic hemorrhage / 重庆医学

Objective To analyse the relationships between islet β-cell function and infection,inflammation and major organ function in multiple organ dysfunction syndrome (MODS) patients with severe traumatic hemorrhage.Methods A total of 187 cases of MODS patients hospitalized in the 94th Hospital of PLA from January 2013 to January 2016 were selected,and were divided into the MODS survival group (MODS-S group,104 cases) and MODS dead group (MODS-D group).Other 100 healthy subjects were selected as the control group.The fasting blood glucose (GLU0) and insulin (INS0) levels,blood glucose (GLU30) and insulin (INS30) levels after 30 min of glucose loading,and levels of soluble triggering receptor expressedon myeloid cells-1 (sTREM-1),tumor necrosis factor-α (TNF-a),interleukin-6 (IL-6),alanine aminotransferase (ALT),creatinine (Cre) and creatine kinase isoenzyme (CK-MB) in different groups were determined.The insulin-β-cell function was evaluated by homeostasis model assessment of β-cell function (HOMA-β) index and ratio of insulin increment and blood glucose increment after 30 min of glucose loading (ΔINS30/ΔGLU30),and their relationships to other indexes,including sTREM-1,TNF-α,IL-6,GLU0,ALT,Cre and CK-MB,in MODS patients with severe traumatic hemorrhage were analysed.Results The HOMA-β and AINS30/AGLU30 ratio in the MODS-D group were lower than those in the MODS-S group,and levels of sTREM-1,TNF-α,IL-6,ALT,Cre and CK-MB in the MODS-D group were higher than those in the MODS-S group,there were statistically significant differences (P＜0.01).In MODS patients with severe traumatic hemorrhage,HOMA-β and ΔINS30/AGLU30 was both negatively correlated with sTREM-1,TNF-α,IL-6,GLU0,ALT,CreandCK-MB (r=-0.356 4,-0.532 1,-0.345 8,-0.772 1,-0.762 5,-0.684 8,-0.606 4;r=-0.428 5,-0.567 8,-0.487 0,-0.743 6,-0.781 7,-0.717 6,-0.640 1,P＜0.01).Conclusion MODS patients with severe traumatic hemorrhage have islet β-cell dysfunction which may be used as a prognostic and diagnostic indicator.

Influence of rat pancreatic islet α cells and its secretions in function of β cells / 吉林大学学报(医学版)

Objective:To investigate the influence of α cells and glucagon-like peptide l (GLP-1) in the function of β cells (INS-1 cells) in the rats,and to elucidate the possible mechanism of α cells and INS-1 cells transplantation in influencing hypoglycemia.Methods:The proliferation abilities of INS-1 cells after treated with 10％,20％ and 30％ islet α-cell conditioned medium and 0.03,0.30,3.00,30.0 mg · L-1 of GLP-1 were analyzed by MTT assay.The levels of insulin secretion of INS-1 cells after treated with 10％,20％,30％ α cells,α-cell conditioned medium and different concentrations of GLP-1 were analyzed by enzyme linked immunosorbent assay (ELISA).The concentrations of Ca2+ in INS-1 cells after treated with high glucose and GLP-1 were analyzed by laser confocal microscope.The expression levels of insulin protein after treated with different concentrations of islet α-cell conditioned medium and different concentrations of GLP-1 were detected by Western blotting methed.After the INS-1 cells,the mixture of INS-1 cells and α cells were transplanted into the left renal capsule of the nude mice,the blood glucose levels and the kidney morphology were observed.The levels of insulin/glucagon in the transplanted cells were detected by immunohistochemistry.Results:Compared with control group,both of α-cell conditioned media and GLP-1 promoted the INS-1 cell proliferation and insulin secretion (P ＜ 0.05).The laser confocal microscope results revealed that GLP-1 stimulated the increased intracellular Ca2+ concentration in INS-1 cells (P＜ 0.05).Compared with control group,there was no significant difference in the expression levels of insulin protein in the insulin-1 cells after treated with islet α cell conditioned medium and GLP-1 (P＞0.05).Compared with pre transplantation,the blood glucose level in the transplanted INS-1 cells was significantly decreased at 35 d after renal capsul trasplantation (P＜0.05),and even hypoglycemia presented renal capsular in the diabetic nude mice;the transplantation site was obviously swollen.However,the levels of blood glucose had no change of the diabetic rats after transplated with the mixture of INS-1 and α cells (P＜0.05).The expression of insulin and glucagon in the INS-1 transplanted cells were found by immunohistochemistry staining.Conclusion:Pancreatic islet α cells and their secretions can promote the INS-1 cell proliferation and insulin secretion,and the mixture of INS-1 cells and α cells transplanted under the renal capsule of the diabetic nude mice can reduce the hypoglycemic effect of INS-1 cell transplantation which might be related to the INS-1 cells that can express both of insulin and glucagon genes.

Influence of rat pancreatic islet α cells and its secretions in function of β cells / 吉林大学学报(医学版)

Objective:To investigate the influence of α cells and glucagon-like peptide l (GLP-1) in the function of β cells (INS-1 cells) in the rats,and to elucidate the possible mechanism of α cells and INS-1 cells transplantation in influencing hypoglycemia.Methods:The proliferation abilities of INS-1 cells after treated with 10％,20％ and 30％ islet α-cell conditioned medium and 0.03,0.30,3.00,30.0 mg · L-1 of GLP-1 were analyzed by MTT assay.The levels of insulin secretion of INS-1 cells after treated with 10％,20％,30％ α cells,α-cell conditioned medium and different concentrations of GLP-1 were analyzed by enzyme linked immunosorbent assay (ELISA).The concentrations of Ca2+ in INS-1 cells after treated with high glucose and GLP-1 were analyzed by laser confocal microscope.The expression levels of insulin protein after treated with different concentrations of islet α-cell conditioned medium and different concentrations of GLP-1 were detected by Western blotting methed.After the INS-1 cells,the mixture of INS-1 cells and α cells were transplanted into the left renal capsule of the nude mice,the blood glucose levels and the kidney morphology were observed.The levels of insulin/glucagon in the transplanted cells were detected by immunohistochemistry.Results:Compared with control group,both of α-cell conditioned media and GLP-1 promoted the INS-1 cell proliferation and insulin secretion (P ＜ 0.05).The laser confocal microscope results revealed that GLP-1 stimulated the increased intracellular Ca2+ concentration in INS-1 cells (P＜ 0.05).Compared with control group,there was no significant difference in the expression levels of insulin protein in the insulin-1 cells after treated with islet α cell conditioned medium and GLP-1 (P＞0.05).Compared with pre transplantation,the blood glucose level in the transplanted INS-1 cells was significantly decreased at 35 d after renal capsul trasplantation (P＜0.05),and even hypoglycemia presented renal capsular in the diabetic nude mice;the transplantation site was obviously swollen.However,the levels of blood glucose had no change of the diabetic rats after transplated with the mixture of INS-1 and α cells (P＜0.05).The expression of insulin and glucagon in the INS-1 transplanted cells were found by immunohistochemistry staining.Conclusion:Pancreatic islet α cells and their secretions can promote the INS-1 cell proliferation and insulin secretion,and the mixture of INS-1 cells and α cells transplanted under the renal capsule of the diabetic nude mice can reduce the hypoglycemic effect of INS-1 cell transplantation which might be related to the INS-1 cells that can express both of insulin and glucagon genes.

MicroRNAs with the Regeneration and Differentiation of Islet β cells and the Targeted Therapy of Traditional Chinese Medicine / 世界科学技术-中医药现代化

MicroRNAs (miRNAs) are a class of non-coding RNAs about 18-25 nucleotides in length,involved in post-transcriptional genes regulation process.Previous studies showed that miRNAs played an important regulatory role in pancreatic development,gene expression,and synthesis and secretion of insulin.A variety of miRNAs which expressed in islet β cells may affect the proliferation and differentiation of islet β cells.Since miRNAs showed tissue specificity,their expression changes were closely related to some diseases.Thus,integrative studies with miRNAs over the essence of syndromes of traditional Chinese medicine could provide new ideas for the treatment of diabetes.