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Objective To analyze the relationship between the expression of hsa_circ_401724 and the in-flammatory response in type 2 diabetes mellitus(T2DM)patients and pancreatic islet cell function.Methods A total of 102 patients with T2DM treated in Linfen Central Hospital from April 2017 to December 2022 were selected as the observation group,and 100 healthy subjects with normal glucose tolerance were se-lected as the control group during the same period.The levels of tumor necrosis factor α(TNF-α),interleukin-6(IL-6)and intercellular adhesion molecule-1(ICAM-1)in the blood of the subjects were detected by en-zyme-linked immunosorbent assay to evaluate the levels of inflammatory factors in the subjects.The relative expression level of hsa_circ_401724/U6 was calculated according to the dissolution curve,and the pancreatic islet cell function of the subjects was assessed,including homeostasis model assessment of insulin resistance(HOMA-IR)and homeostatic model assessment beta cell function(HOMA-β)as assessed by homeostasis model.Pearson correlation was used to analyze the correlation between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function,and Logistics regression model was used to analyze the rela-tionship between hsa_circ_401724 expression level and inflammation and pancreatic islet cell function.Results The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in observation group were significantly higher than those in control group,while the levels of HOMA-β in observation group were significantly lower than those in control group,with statistical significance(P<0.05).The relative expression level of hsa_circ_401724 in observation group(0.75±0.13)was significantly higher than that in control group(0.24±0.06),and the difference was statistically significant(P<0.05).The levels of HOMA-IR,TNF-α,IL-6 and ICAM-1 in hsa_circ_401724 high expression group were significantly higher than those in hsa_circ_401724 low expres-sion group,and the levels of HOMA-β were significantly lower than those in hsa_circ_401724 low expression group.The difference was statistically significant(P<0.05).The relative expression level of hsa_circ_401724 was positively correlated with the levels of HOMA-IR,TNF-α,IL-6 and ICAM-1(r=0.657,0.671,0.703,0.698,P<0.05).hsa_circ_401724 expression level was negatively correlated with HOMA-β level(r=-0.611,P<0.05).The high expression of hsa_circ_401724 was an independent risk factor affecting the levels of HOMA-IR,HOMA-β,TNF-α,IL-6 and ICAM-1 in T2DM patients(P<0.05).Conclusion The high ex-pression of hsa_circ_401724 is related to the inflammatory response and the decline of pancreatic islet cell function in T2DM patients.
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Objective:To investigate the relationship between the expression level of circular RNA_0005414 and islet cell function in type 2 diabetes patients.Methods:A total of 110 patients with type 2 diabetes and 106 cases of normal glucose tolerance (control group) in Uygur populations, 64 cases of type 2 diabetes mellitus and 63 cases of normal glucose tolerance (control group) in Han populations were enrolled in the study. All subjects underwent oral glucose tolerance test chemistry panel. Homeostasis model assessment for insulin resistance (HOMA-IR) and β cell function (HOMA-β) were evaluated by homeostasis model as islet cell function indexes. The differentially expressed circular RNAs were screened using RNA sequencing from the peripheral blood monocytes of 5 Uygur patients with type 2 diabetes mellitus and matched controls. The expression level of a significantly up-regulated circular RNA_0005414 was detected and verified, and the relationship between the expression level of circular RNA_0005414 and islet cell function was analyzed.Results:Differential expression profiles of circular RNAs were found in Uygur type 2 diabetic patients . The expression level of circular RNA_0005414 in Uygur type 2 diabetic group was higher than that in Uygur control group ( P<0.01), the expression level of circular RNA_0005414 in Han type 2 diabetic group was higher than that in Han control group ( P<0.01), the expression level of circular RNA_0005414 in Uygur type 2 diabetes group was higher than that in Han type 2 diabetes group, but the difference was not statistically significant ( P>0.05). In the Uyghur and Han groups, Spearman correlation analysis showed that the expression level of circular RNA_0005414 was positively correlated with fasting blood glucose, 2 h plasma glucose after glucose loading, HbA 1C, total cholesterol, fasting insulin, HOMA-IR ( P<0.05) and negatively correlated with HOMA-β ( P<0.01). Partial correlation analysis showed that circular RNA_0005414 expression level was positively correlated with fasting blood glucose, HbA 1C, and HOMA-IR ( P<0.01). Multivariate linear regression analysis showed that circular RNA_0005414 was the only factor affecting HOMA-β in Uygur patients with type 2 diabetes. Conclusion:The expression level of circular RNA_0005414 was closely related to islet cell function in Uygur type 2 diabetes patients, the up-regulation of circular RNA_0005414 may be involved in the occurrence and development of type 2 diabetes in Uygur.
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Studies on islet of Langerhans physiology are crucial to understand the role of the endocrine pancreas in diabetes pathogenesis and the development of new therapeutic approaches. However, so far most research addressing islet of Langerhans biology relies on islets obtained via enzymatic isolation from the pancreas, which is known to cause mechanical and chemical stress, thus having a major impact on islet cell physiology. To circumvent the limitations of islet isolation, we have pioneered a platform for the study of islet physiology using the pancreas tissue slice technique. This approach allows to explore the detailed three-dimensional morphology of intact pancreatic tissue at a cellular level and to investigate islet cell function under near-physiological conditions. The described procedure is less damaging and faster than alternative approaches and particularly advantageous for studying infiltrated and structurally damaged islets. Furthermore, pancreas tissue slices have proven valuable for acute studies of endocrine as well as exocrine cell physiology in their conserved natural environment. We here provide a detailed protocol for the preparation of mouse pancreas tissue slices, the assessment of slice viability, and the study of pancreas cell physiology by hormone secretion and immunofluorescence staining.
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Histocytological Preparation Techniques/methods , Islets of Langerhans/physiology , Pancreas/cytology , Tissue Culture Techniques/methods , Animals , Cell Survival/physiology , Fluorescent Antibody Technique/methods , Insulin Secretion/physiology , Mice , Microfluidic Analytical Techniques/methods , Tissue and Organ HarvestingABSTRACT
Objective To investigate the effects of vitamin D3 supplementation combined with standard-ized hypoglycemic regimen on islet β cell function and macroangiopathy of T2DM patients. Methods A total of 192 patients with type 2 diabetes mellitus were selected and randomly divided into control group and observation group with 96 patients in each group. Patients in two groups were given standardized hypoglycemic regimen, and the observation group was treated with vitamin D3 supplementation in addition. The changes of the indexes of body examination, glycolipid metabolism, islet β cell function and macrovascular complications before and 6 months after treatment were compared between the two groups. Results After 6 months of treatment, BMI, SBP, TG, FBG, FINS, HbA1c and HOMA-IR decreased, while HOMA-β increased in both groups ( P<0. 05) . Compared with the control group, the serum levels of 25 ( OH) D increased, and vaspin and CRP de-creased significantly after 6 months of treatment in the observation group ( P<0. 05) . CIMT and other indicators showed no significant difference. 25 (OH) D was negatively correlated with FBG, FINS, vaspin and CRP, and positively correlated with 1PH and ISI (P<0.05). Conclusion Vitamin D3 is closely related to T2DM and its macrovascular complications, but it has not been found that vitamin D3 supplementation can further improve islet β cell function and macrovascular complications in patients with T2DM.
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Objective To investigate the clinical efficacy of entecavir in the treatment of hepatitis B cirrhosis associated with hepatic diabetes. Methods 78 cases of hepatitis B Hepatic Cirrhosis with diabetes were selectedfrom June 2015 to December 2016, and randomly divided into study group (n=39) and control group (n=39). The study group were treated with entecavir, the control group were treated with adefovir dipivoxil. Two groups of patients with hepatitis B cirrhosis combined with hepatic diabetes were treated continuously for 48 weeks, the changes of FPG, HOMA-β, beta and HOMA-IR were recorded. Results There was no significant difference between the two groups in the treatment of FPG, HOMA-β, and HOMA-IR. After treatment, the two groups of FPG and HOMA-IR decreased significantly compared with before treatment, while HOMA-β was significantly higher than before treatment, but the changes of the above indexes in the study group were better than those in the control group (P<0.05). Conclusion Entecavir combined with hypoglycemic agents can achieve more ideal blood glucose control effect in patients with hepatitis B cirrhosis combined with hepatic diabetes..
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Objective To investigate the clinical efficacy of entecavir in the treatment of hepatitis B cirrhosis associated with hepatic diabetes. Methods 78 cases of hepatitis B Hepatic Cirrhosis with diabetes were selectedfrom June 2015 to December 2016, and randomly divided into study group (n=39) and control group (n=39). The study group were treated with entecavir, the control group were treated with adefovir dipivoxil. Two groups of patients with hepatitis B cirrhosis combined with hepatic diabetes were treated continuously for 48 weeks, the changes of FPG, HOMA-β, beta and HOMA-IR were recorded. Results There was no significant difference between the two groups in the treatment of FPG, HOMA-β, and HOMA-IR. After treatment, the two groups of FPG and HOMA-IR decreased significantly compared with before treatment, while HOMA-β was significantly higher than before treatment, but the changes of the above indexes in the study group were better than those in the control group (P<0.05). Conclusion Entecavir combined with hypoglycemic agents can achieve more ideal blood glucose control effect in patients with hepatitis B cirrhosis combined with hepatic diabetes..
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BACKGROUND: The goal of this study was to investigate the effects of linagliptin compared with glimepiride on alpha and beta cell function and several vascular biomarkers after a standardized test meal. METHODS: Thirty-nine patients on metformin alone (age, 64 ± 7 years; duration of type 2 diabetes mellitus, 7.8 ± 4.5years, 27 male, 12 female; HbA1c , 57.2 ± 6.9 mmol/mol; mean ± SD) were randomized to receive linagliptin 5 mg (n = 19) or glimepiride (n = 20) for a study duration of 12 weeks. Glucagon-like peptide 1, blood glucose, insulin, intact proinsulin, glucagon, plasminogen activator inhibitor-1 (PAI-1), cyclic guanosinmonophosphat and asymetric dimethylarginin levels were measured in the fasting state and postprandial at 30-min intervals for a duration of 5 h. The areas under the curve (AUC0-300 min ) were calculated for group comparisons. RESULTS: HbA1c , fasting and postprandial glucose levels improved in both groups. An increase in postprandial insulin (22595 ± 5984 pmol/L*min), postprandial intact proinsulin (1359 ± 658 pmol/L*min), postprandial glucagon (317 ± 1136 pg/mL*min) and postprandial PAI-1 levels (863 ± 467 ng/mL*min) could be observed during treatment with glimepiride, whereas treatment with linagliptin was associated with a decrease in postprandial insulin (-8007 ± 4204 pmol/L*min), intact proinsulin (-1771 ± 426 pmol/L*min), postprandial glucagon (-1597 ± 1831 pg/mL*min) and PAI-1 levels (-410 ± 276 ng/mL*min). CONCLUSIONS: Despite an improvement in blood glucose control in both groups, linagliptin reduced postprandial insulin, proinsulin, glucagon and PAI-levels. These results indicate an improvement in postprandial alpha and beta cell function, as well as a reduced postprandial vascular risk profile during treatment with linagliptin.
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Blood Glucose/metabolism , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Islets of Langerhans/physiology , Metformin/therapeutic use , Postprandial Period/physiology , Purines/therapeutic use , Quinazolines/therapeutic use , Sulfonylurea Compounds/therapeutic use , Aged , Biomarkers/blood , Cardiovascular Diseases/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Drug Therapy, Combination , Female , Glucagon/blood , Glucagon-Like Peptide 1/blood , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Insulin/blood , Islets of Langerhans/drug effects , Linagliptin , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Proinsulin/blood , Purines/pharmacology , Quinazolines/pharmacology , Risk Factors , Sulfonylurea Compounds/pharmacologyABSTRACT
Objective To evaluate the features of insulin sensitivity and ?-cell function in a Chinese population with normal fasting glucose.Methods 2,388 subjects aged≥20 years were divided into 5 groups based on the results of oral 75-g glucose tolerance test(OGTT):low-NFG,mid-NFG,high-NFG,IFG,T2DM.We compared insulin secretion and insulin sensitivity using several indexes derived from OGTT.Results There was a progressive decline in indexes of ?-cell function and insulin sensitivity when moving from NFG to type 2 diabetes.Compared with subjects with mid-NFG(FPG 4.9~5.6mmol/l),subjects with high-NFG(FPG5.6~6.1mmol/l)were more resistant to insulin,and had reduced insulin secretion,higher plasma triglyceride level and reduced HDL cholesterol concentrations(P
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Objective To evaluate the changes of β cell function in critically ill surgical patients and its re- lationship with prognosis.Methods 32 patients>16 years age with no history of diabetes who were admitted to sur- gical intensive care unit(SICU)were divided into two groups according to APACHE Ⅱ score.Blood sample Was taken on preoperative and postoprative 1st day for measures of fasting insulin(FINS)and fasting C peptide(FCP). The HOMA-β Was calculated.Results The level of FINS,FCP and HOMA-β were significantly decreased on first day after operation than preoperative in critical group.Compared with control group,The level of FINS.FCP and HO- MA-βwere significantly reduced on first day after operation-which had negative correlation with APACHE Ⅱ score, APACHE Ⅲ score and in charge days of ICU.Conclusion There is β cell dysfunction in critically ill Surgical pa- tients.β cell function in surgical critically ill patients is negatively correlated with APACHE Ⅱ SCOre-APACHE Ⅲ score and days of ICU.
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Objective:To investigate insulin resistance(IR) and islet ?-cell function in nondiabetic first-degree relatives(FDR) of patients in type 2 diabetes(T2DM) families.Methods:195 FDR with impaired glucose regulation(FIGR group),232 FDR with normal glucose tolerance(FNGT group) and 161 NGT spouses of probands or siblings(NC group),which come from 251 T2DM families including at least two T2DM patients in Chongqing district,were selected.The subjects of FIGR group were divided into 3 groups: isolated impaired fasting glucose(iIFG),isolated impaired glucose tolerance(iIGT) and combined IFG and IGT(IFG/IGT).For all subjects,75 gram oral glucose tolerance tests were conducted.Blood glucose,lipid-profile and insulin were assayed.Homeostasis model assessment of insulin resistance(Homa-IR) was used to estimate insulin resistance,and disposition index(DI) was used to evaluate islet ?-cell function(DI1=Homa-?/ Homa-IR,DI2=△I30/△G30/ Homa-IR).Results:(1)After adjustment of age,sex and body mass index(BMI),compared with NC group,systolic blood pressure and Homa-IR increased and DI1 decreased in FNGT group and the difference was significant(P﹤0.05).Systolic blood pressure,triglyceride,plasma glucose and serum insulin levels during OGTT and Homa-IR of FIGR group were higher than those of NC group;while Homa-?,△I30/△G30,DI1 and DI2 of FIGR group were lower,and the difference was significant(P﹤0.01).(2)iIGT and IFG/IGT had higher plasma glucose at 60min and 120min,serum insulin at 120min during OGTT compared with iIFG(P﹤0.01),and the difference was significant.Compared with iIGT,Homa-IR increased and Homa-?,DI1 decreased in iIFG and IFG/IGT,and the difference was significant(P﹤0.05).DI2 of iIFG,iIGT and IFG/IGT decreased in turn.DI2 of IFG/IGT was much lower than that of the two formers,and the difference was significant(P﹤0.01).Conclusion:Non-diabetic FDR of T2DM patients presented IR and disfunction of ?-cell.
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0.05). But the level of HbA1c, 2 hour insulin and C peptide were significantly lower than that in CG (P 0.05). Conclusion Wei li acupuncture therapy instrument can improvement the islet ?-cell function in patients with type 2 diabetes mellitus.
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Objective To observe the effect of berberine to islet ?-cell function in type 2 diabetes mellitus (damp-heat type). Methods 60 patients with type 2 diabetes mellitus (damp-heat type) were randomly divided into 2 groups, under basic treatment of 2 weeks with metformin, the treatment group was given berberine. After 8 weeks, the changes in the levels of blood glucose, insulin, HbA1c, CRP and the grade of traditional Chinese medicine individual event symptom and general integral symptom were observed. Apply the formular to evaluate the pancreas's function. Results Each group had notable difference before and after the experiment in many aspects, especially in treatment group. There was a notable difference in 2 groups. Conclusion Berberine has obvious effect on increasing insulin releasing level, improving insulin sensibility, lightening insulin resistance and improving islet ?-cell function.
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Objective To evaluate insulin resistance and ?-cell function in patients with systemic lupus erythematosus(SLE).Methods The study group included thirty-two female SLE patients who were hospitalized or received outpatient treatment in our hospital;the control group consisted of twenty-two healthy females.Their fasting plasm glucose and serum insulin were all tested.Homeostasis model assessment(HOMA) was used to calculate HOMA-IR and HOMA-?-cell function,and these parameters were compared between the study group and control group.Results Compared with control group,the SLE patients had significantly higher fasting insulin levels(12.13?4.32 vs.8.84?2.19,P0.05).Conclusion Patients with SLE have a higher risk of insulin resistance and abnormal insulin secretion than controls.
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Diabetic patients with secondary sulfonylureas failure were shifted to glipizide plus glargine ( n = 20) or neutral protamine hagedorn (n =32). Sixteen weeks later, blood glucose and HbAIC were decreased and serum C peptide level increased in both groups. Hypoglycemia occurred less frequently and?-cell function was improved in glargine group.
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Hyperglycaemia attenuates?-cell insulin secretion in response to plasma glucose elevation and reduces insulin-mediated glucose transport. The long-standing severe hyperglycaemia may irreversibly damage?-cells. However, in this regard, there are increasing evidences showing that short-term intensive insulin therapy may significantly improve the response to endogenous insulin by normalizing blood glucose, so as to induce a "honeymoon period" for several years in a considerable number of subjects with newly diagnosed type 2 diabetes. Thus, a question has been raised: whether or not insulin therapy should be taken as a part of the strategy of the primary treatment for type 2 diabetes? A number of experts believe that it is an important therapeutic strategy, however, others hold that insulin therapy may yield more cost than benefit and suggest that to halt this cycle of progressive metabolic deterioration by any means may transiently restore metabolic re-compensation in type 2 diabetes. This issue was discussed in the fourth meeting of China Group on Insulin Secretion and in 66th ADA scientific session this year. Here we offer our consideration on this question for your reference.
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Objective To study the characteristics of ? cell function change and to explore the predictive value of glutamic acid decarboxylase (GAD)-Ab and other factors for ? cell function in the patients with latent autoimmune diabetes of adults (LADA). Methods Sixteen LADA patients (positive GAD-Ab) and 24 type 2 diabetic patients (negative GAD-Ab) were followed-up at 0, 6th, 12th, 30th, 36th, 42th and 48th months respectively. Their fasting and postprandial 2h C-peptide and glycemic control were measured. GAD-Ab was determined by radioimmunoprecipitation assay and C-peptide by RIA. Results Decreased fasting C peptide (FCP) levels (Month 30, 36, 42, 48 compared with Month 0, P
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The results observed in normal weight group (81 subjects), simple obese group (140 subjects) and hyperglycemic obese group (97 subjects) showed that there was a significantly positive correlation between ? cell function and endothelium-dependent vasodilation function (EDV) in hyperglycemic obese group (r=0.52, P