Islet transplantation has the potential to restore normoglycemia and prevent the development of diabetic complications such as retinopathy, nephropathy and neuropathy, and could therefore ve a valuable treatment for diabetic patients. The scarcity of available islets is an obstacle for clinically successful islet transplantation. To resolve the problems, we have examined the two methods, islet transplantation with extracellular matrix1 and in vivo expansion of islets with electrically- transfection of growth factors.
Animals ; Diabetes Mellitus/surgery/*therapy ; Fibronectins/therapeutic use ; Hepatocyte Growth Factor/genetics ; Islets of Langerhans/drug effects/*physiopathology ; *Islets of Langerhans Transplantation ; Male ; Rats ; Rats, Wistar ; *Regeneration ; Transfection

The nature history of type 2 diabetes is characterized by the interaction between beta-cells function and insulin sensitivity. Normal glucose tolerance could be maintained when there is a balance between insulin sensitivity and beta-cells function. For most of type 2 diabetic patients, both defects in insulin secretion as well as insulin action are needed for the development of diabetes. In addition, there is abundant evidence indicating the importance of genetic factors in the development of type 2 diabetes, including data from the twin studies, family studies, studies among different ethnic groups living in the same environment and admixture studies. In the last two decades, that genetic defects affecting both beta-cells function and insulin sensitivity has been identified. But those defects can only explain a very small portion of etiology of type 2 diabetes, and the gene defects contributing to the cause of most type 2 diabetes are still at large. We have learned, from the past experience that type 2 diabetes is a very heterogeneous and complex disease. The complexity of type 2 diabetes is related to factors such as genetic heterogeneity, interactions between genes, and the modulating role played by the environment.
Animals ; Diabetes Mellitus, Type 2 ; etiology ; genetics ; Humans ; Insulin Resistance ; Islets of Langerhans ; physiopathology

OBJECTIVEThe strong relation between type 2 diabetes mellitus and obesity with acanthosis nigricans is widely concerned. This study investigated the pancreatic beta-cell function in obese children with acanthosis nigricans, so as to find out the role of insulin secretion and insulin resistance in obese children with acanthosis nigricans.

METHODSThirty-five obese children with acanthosis nigricans (19 males and 16 females with mean age 12.8 +/- 1.5 years) were enrolled in this study. Thirty-eight obese children (21 boys and 17 girls with mean age 11.9 +/- 2.6 years) and 39 normal children (20 boys and 19 girls with mean age 11.2 +/- 2.2 years) were recruited as obese and normal control groups. The levels of serum fasting insulin, C-peptide, proinsulin and true insulin were measured in all the subjects. The ratios of proinsulin/insulin and proinsulin/C-peptide were calculated. Homeostasis model assessment was applied to assess the status of insulin resistance and basic function of pancreatic beta-cell.

RESULTSThe levels of fasting insulin, C-peptide proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index of obese children with acanthosis nigricans, obese control children and normal control children were: 18.5 (5.0-60.5) pmol/L, 12.4 (6.1-35.8) pmol/L and 5.1 (2.0-32.8) pmol/L; 3.9 (1.3-14.0) microg/L, 2.4 (1.1-4.0) microg/L and 1.1 (1.0-4.2) microg/L; 28.8 (9.9-64.2) pmol/L, 9.5 (2.2-34.5) pmol/L and 4.2 (2.0-16.0) pmol/L; 33.0 (6.2-66.0) pmol/L, 10.6 (4.8-29.4) pmol/L and 4.5 (1.3-30.1) pmol/L; 1.2 (0.4-8.9), 0.9 (0.2-1.9) and 0.8 (0.4-2.0); 6.9 (2.5-36.6), 4.7 (1.2-12.3) and 3.6 (1.2-9.6); 5.0 (0.8-14.1), 2.6 (1.3-8.1) and 1.2(0.4-6.9); 303.3 (52.2-1,163.8), 213.6 (84.6-572.0) and 51.1 (19.1-561.4). The levels of fasting insulin, C-peptide, proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index in obese children with acanthosis nigricans were significantly higher than those in obese children (P < 0.001) and normal children (P < 0.001).

CONCLUSIONObese children with acanthosis nigricans had higher insulin resistance and pancreatic beta-cell dysfunction; acanthosis nigricans may be a skin sign of high risk of type 2 diabetes mellitus.

Acanthosis Nigricans ; complications ; Adolescent ; C-Peptide ; blood ; Child ; Diabetes Mellitus, Type 2 ; etiology ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Islets of Langerhans ; physiopathology ; Male ; Obesity ; complications ; physiopathology ; Proinsulin ; blood

OBJECTIVETo investigate the effect of Cordyceps sinensis (CS) on pancreatic islet B cells of experimental hepatic fibrogenesis rats.

METHODSRats were randomly allocated into three groups: normal group, model group and CS group. The rats in the latter two groups were administered with CCl(4) solution to induce liver fibrosis, the CS group was also treated with CS 10 days after the beginning of CCl(4) administration. Rats in normal group were sacrificed at the beginning of the experiment, while the rats in the other two groups were sacrificed randomly at the end of the third and sixth weeks. The rats' islets were isolated and cultured in vitro, then the basal insulin level of the islets and the serum level of insulin were determined by radioimmunological assay.

RESULTSIt seemed no change that the levels of serum insulin and basal insulin between the model group and the normal group at the third week. But at the sixth week, both insulin levels in the model group were higher than those in the normal group (52.6 mU/L2.5 mU/L vs 23.7 mU/L 2.3 mU/L, q=13.01, p<0.05; 52.94muU/ml 13.12muU/ml vs 35.16muU/ml 5.64muU/ml, q=10.06, p<0.01). No significant change could be seen in the serum levels of insulin between the CS group and the model group at the third and sixth weeks. But the basal insulin levels in the CS group were apparently higher than those in the model group at the third and sixth weeks (156.63muU/ml 6.57muU/ml vs 39.64muU/ml 3.95muU/ml, q=66.94, p<0.001; 140.44muU/ml 38.53muU/ml vs 52.94muU/ml 13.12muU/ml, q=12.98, p<0.01).

CONCLUSIONCordyceps sinensis can increase the basal insulin level of the islets in CCl(4)-induced liver fibrosis rats.

Animals ; Carbon Tetrachloride ; toxicity ; Cordyceps ; Female ; Insulin ; blood ; secretion ; Islets of Langerhans ; physiopathology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; pathology ; physiopathology ; therapy ; Male ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of integrative Chinese and Western medicine (ICWM) on improvement of the islet beta cell function in treating patients with latent autoimmune diabetes mellitus in adults (LADA).

METHODSEighty-four patients of LADA were randomly divided into 3 groups (20 in A, 33 in B and 31 in C), they were treated respectively with sulfonylurea, insulin and combination of insulin and Chinese medicine. The changes before and after treatment in blood glucose, glycohemoglobin and islet beta cell function were observed.

RESULTSAfter treatment, the damaged islet beta cell function in Group A was not improved, the secrete peak value of C-peptide was still low and delayed in Group A, but in Group B and C, it shifted earlier, suggesting that a certain degree of improvement and recovery of islet beta cell function. The improving effect in Group C was better.

CONCLUSIONChinese herbal medicine had effect in lowering blood glucose and improving islet beta cell function in patients with diabetes mellitus, and showed a synergistic and enhancing action when combined use with insulin. Early treatment of insulin or combination of insulin and Chinese medicine should be applied to patients with LADA.

Adult ; Autoimmune Diseases ; drug therapy ; physiopathology ; Blood Glucose ; metabolism ; C-Peptide ; metabolism ; Diabetes Mellitus ; classification ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Insulin ; therapeutic use ; Islets of Langerhans ; physiopathology ; Male ; Middle Aged ; Phytotherapy

OBJECTIVETo investigate the effect and mechanism of Tangyikang (TYK) for improving pancreatic islet beta cell function in patients with latent autoimmune diabetes mellitus in adults (LADA).

METHODSSeventy-four LADA patients were randomly assigned to two groups. The 37 patients in the treatment group were treated with TYK decoction (one dose consisted of red ginseng 10 g, milkvetch root 30 g, lilyturf root 15 g, wild weed 10 g, coptis root 15 g, cape-jasmine fruit 10 g, giant knotweed rhizome 10 g, safflower 10 g and moutan bark 10 g) combined with insulin therapy, and the 37 in the control group treated with insulin therapy alone, and the course for all was 3 months. Changes of glycosylated hemoglobin, index of pancreatic islet beta-cell function (delta CP(2h)/delta BS(2h)), serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were observed before and after treatment.

RESULTSAll the above-mentioned indexes were improved after treatment in both groups, the post-treatment data showed significant difference between groups in delta CP(2h)/delta BS(2h), (0.258 +/- 0.106 vs 0.168 +/- 0.054, higher in the treatment group, t = 4.626, P < 0.01), but with insignificant difference in glycosylated hemoglobin (t = 0.441, P = 0.660). Besides, the dosage of insulin used in the treatment group was less than that in the control group (t = -4.169, P < 0.01); covariance analysis showed, through excluding impact of different dosages insulin used, IL- 4 level was higher (F = 24.217, P < 0.01) and IFN-gamma level was lower (F = 14.198, P < 0.01) in the treatment group than those in the control group.

CONCLUSIONSTYK could improve the function of islet beta-cell, its possible mechanism is related with the regulation on cell immunity and the correction of T-lymphocyte subsets (Th1/Th2 ratio) imbalance.

Adult ; Diabetes Mellitus, Type 1 ; blood ; drug therapy ; immunology ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Islets of Langerhans ; drug effects ; immunology ; physiopathology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo analyze the biochemical and pathological changes in mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet combined with low-dose streptozotocin (STZ) injections.

METHODSC57BL/6J mice were divided randomly into normal control group (NC group), high-fat diet group (HC group) and high-fat diet plus STZ group (HC+STZ group). The mice were fed on normal chow or a high-fat diet for 1 month before two introperitoneal injections of STZ (40 mg/kg) or citrate buffer with an interval of 24 h as appropriate. Fasting blood glucose (FBG) was detected every week for 4 weeks, and oral glucose tolerance test (OGTT) was performed one month after the injections, after which the biochemical profiles, islet and liver were evaluated by immunohistochemical and pathological analysis.

RESULTSIn HC+STZ group, FBG was above the cutoff value (13.89 mmol/L) in 75% of the mice at 1 week after STZ injections and in all the mice at two weeks except for the death of 1 mouse, with a success rate of modeling of 91.3%. FBG in HC group, though slightly higher than that in NC group, remained normal (6.8 mmol/L). The body weight in HC+STZ and HC groups was significantly higher than that in NC group after feeding but without obvious increases after the injections (P<0.01). Blood glucose in HC+STZ group at 0.5 to 2 h after OGTT and the area under curve (AUC) were higher than those in NC and HC groups (P<0.01); the AUC in HC group was a also higher than that in NC group (P<0.05). Plasma creatinine was significantly higher in HC+STZ group than in NC (P<0.01) and HC (P<0.05) groups. Insulin secretion by the islets decreased obviously in HC+STZ and HC group. The mice in HC+STZ group showed atrophy, fibrosis, and vacuolization in the islets with mild fatty liver but no visible renal pathologies.

CONCLUSIONHigh-fat diet and low-dose STZ injections can induce T2DM in mice with very similar biochemical and pathological changes to human T2DM and with such complications as fatty liver.

Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2 ; physiopathology ; Diet, High-Fat ; Fatty Liver ; physiopathology ; Glucose Tolerance Test ; Insulin ; Insulin Resistance ; Islets of Langerhans ; pathology ; Kidney ; pathology ; Mice ; Mice, Inbred C57BL ; Streptozocin

BACKGROUND: Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. METHODS: We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also investigated the relationship between serum insulin, proinsulin and proinsulin/insulin ratio and several biochemical markers which represent insulin resistance or beta cell function. RESULTS: Insulin, proinsulin and proinsulin/insulin ratio were significantly higher in type 2 DM than control(p < 0.001). In diabetic patients, total insulin level was correlated with urinary albumin excretion rates(r = 0.224, p = 0.025) and body mass index(r = 0.269, p = 0.014). Proinsulin level was correlated with fasting C-peptide(r = 0.43, p = 0.002), postprandial 2 hour blood glucose(r = 0.213, p = 0.05) and triglyceride(r = 0.28, p = 0.022). Proinsulin/insulin ratio was positively correlated with fasting C-peptide(r = 0.236, p = 0.031), fasting blood glucose (r = 0.264, p = 0.015), postprandial 2 hour blood glucose(r = 0.277, p = 0.001) and triglyceride(r = 0.428, p < 0.001). In control subjects, insulin level was correlated with triglyceride(r = 0.366, p = 0.002). Proinsulin/insulin ratio was correlated with age(r = 0.241, p = 0.044). CONCLUSION: The serum levels of insulin and proinsulin seem to be associated with several markers of insulin resistance. Whereas proinsulin/insulin ratio might represent beta cell function rather than insulin resistance. But more studies are needed to clarify the mechanisms of elevated proinsulin/insulin ratio in type 2 DM.
Aged ; Diabetes Mellitus, Non-Insulin-Dependent/etiology ; Diabetes Mellitus, Non-Insulin-Dependent/blood* ; Female ; Human ; Insulin/blood* ; Insulin Resistance* ; Islets of Langerhans/physiopathology* ; Male ; Middle Age ; Proinsulin/blood* ; Sulfonylurea Compounds/pharmacology

OBJECTIVETo investigate the effect of N-acetyl-l-cysteine (NAC) on islet beta cell function in hyperlipidemic rats and its mechanism.

METHODSFifty-nine male SD rats of 8 week old were randomly divided into 3 groups: normal diet group(NC, n=20), high fat diet group (HF, n=20) and NAC treated group (NAC, n=19, NAC 300 mg x kg(-1) x d(-1) and high fat diet). At the end of 20 weeks, fasting serum insulin (Ins), glucose(Glu), malonaldehyde (MDA) and reduced glutathione (GSH) were determined in plasma and pancreas tissue. The glucose infusion rate (GIR) was measured by euglycemic hyperinsulinemia clamp to evaluate the peripheral insulin resistance.Pancreatic islets were isolated and subjected to a perifusion medium containing 3.3 mmol/L glucose for 15 min, followed by 16.7 mmol/L glucose for 30 min, insulin content of perifusion medium was measured by RIA. The expressions of IRS-1, IRS-2, Glut-2 gene in islets were detected by real time PCR.

RESULTS(1)The insulin, glucose and MDA concentration in HF group were higher than those in NC group, but GSH levels in plasma and pancreas were lower. NAC intervention could reverse these effects. (2)The GIR was decreased significantly in HF group compared with NC group [(5.25 +/-1.2) Compared with (13.56 +/-1.7) mg x min(-1) x kg(-1), P<0.01], NAC intervention reversed these effect: GIR[(9.28 +/-1.50) Compared with (5.25 +/-1.2)mg x min(-1) x kg(-1), P<0.01]. (3) 16.7 mmol/L glucose increased the insulin secretion in the islet cells of the three groups, but the peak was lower in HF group. NAC intervention reversed these effects. (4) The gene expression of IRS-1 was significantly decreased by 42.3 % in HF group (P<0.05), and the expressions of IRS-2 and Glut-2 were decreased by 28.1% and 22.9% (P<0.05) compared with NC group. In contrast, the expressions of IRS-1, IRS-2, Glut-2 in NAC group increased by 40.2%, 30.2% and 19.1%, respectively than those in HF group.

CONCLUSIONNAC can reverse functional disorder of islet beta cells induced by high-fat-diet feeding. This antioxidant effect might be associated with upgrading gene expression of insulin signal transduction molecules in islet beta cells.

Acetylcysteine ; pharmacology ; Animals ; Dietary Fats ; administration & dosage ; Free Radical Scavengers ; pharmacology ; Hyperlipidemias ; metabolism ; physiopathology ; Insulin Resistance ; Islets of Langerhans ; drug effects ; secretion ; Male ; Oxidative Stress ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

This investigation was directed to the metabolic syndrome and the islet beta-cell secretory function in the first-degree relatives (FDR) of type 2 diabetic patients in Sichuan province. A large cohort study was designed. Totally 1929 subjects were investigated. They were in two groups: FDR group comprising 505 first-degree relatives of type 2 diabetic patients, and Control group comprising 1424 controls without positive family history of Diabetes. Blood pressure, weight, waist, plasma glucose, lipids and insulin were measured. HOMA-IR and HOMA-beta indexes were used to evaluate insulin resistance and beta-cell secretion function. The insulin sensitivity index (ISI) and glucose disposition index (DI) were also used to evaluate insulin resistance. After adjustment for age and sex, HOMA-IR increased, ISI, DI and HOMA-beta decreased in FDR group when compared with controls (P < 0.05). The incidence of co-existed three or more metabolic disorders and metabolic syndrome was higher in FDR group than that in control group (P < 0.05). In FDR group, HOMA-IR increased, HOMA-beta, DI and ISI decreased while the number of co-existing metabolic disorders increased. But when the number of co-existing metabolic disorders > or = 4, HOMA-IR increased no longer and ISI decreased no more. Metabolic disorders occurred more frequently in FDR of diabetic patients than those in individuals without positive family history. As the number of co-existing metabolic disorders increased, the beta-cell secretion function and insulin sensitivity became worse. Our study indicated that it is necessary to keep on monitoring the metabolic index in FDR of type 2 diabetes and provide early preventive interventions.
Adult ; China ; epidemiology ; Cohort Studies ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; Islets of Langerhans ; physiopathology ; Male ; Metabolic Syndrome ; epidemiology ; genetics ; Middle Aged ; Surveys and Questionnaires