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Objective To explore the associations between polymorphisms of Vitamin D receptor gene and type 1 diabetes susceptibility. Methods Literatures were retrieved from PubMed ,Web of Science and WanFang databases ,etc.Pooled odds ratios(ORs) with 95% confidence intervals (CIs) were calculated using a random effect model. Results A total of 28 literatures were included. The result of analysis showed that BsmI and ApaI polymorphism were the susceptibility gene for T 1DM in Asian populations [B vs b;OR(95% CI)=1.53(1.06~2.20) ,P=0.024 ;AA vs aa:OR(95% CI)=1.60(1.06~2.40) ,P= 0.023]. Conclusion The BsmI and ApaI polymorphism may be susceptibility gene in Asians populations with T1DM.
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ObjectiveTo explore whether the biocompatibility of phosphorylcholine (PC) modified alginate-chitosan microcapsules could be improved. MethodsPC modified alginate-chitosan microcapsules were obtained by high-voltage electrostatic system.Bradford method was adopted to determine the adsorption amounts of bovine serum albumin by chitosan alone and PC modified chitosan.Alginate-chitosan-PC microcapsules (experimental group) and alginate-chitosan microcapsules ( control group) were respectively implanted into the peritoneal cavity of mice and retrieved 4 weeks after transplantation.Fibrosis of the capsules was evaluated by HE staining.Glucose stimulated insulin secretion (GSIS) assay was used to assess the insulin secretion response of encapsulated and nonencapsulated rat islets. Results The adsorption amount of protein was 189.4 μg/mg and 90.5 μg/mg respectively by chitosan alone and PC modified chitosan.The difference had statistical significance ( t =5.549, P ＜ 0.05 ).In contrast to the control group, the cellular reaction on the surface of the modified microcapsules was weaker, with no obvious fibrosis found.The insulin secreted by encapsulated islets and nonencapsulated islets was( 3.298 ± 1.680 ) μIU/ml VS (4.299 ± 1.159 ) μIU/ml ( t =1.096, P ＞ 0.05 ) in response to low-glucose stimulus and( 11.783 ± 4.175 ) μIU/ml VS ( 12.875 ± 2.268 ) μIU/ml ( t =0.514, P ＞ 0.05 ) in response to high-glucose stimulus.Conclusions PC can improve the biocompatibility of alginate-chitosan microcapsules, with no effect on the biological function of encapsulated islets.It may be more appropriate to use modified microcapsules encapsulating islets for transplantation.
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Objective To compare the effects of intermittent high blood glucose and consistent hilgh blood glucose on pancreatic islet β-cell function and β-cell apoptosis in GK rats.Methods Twenty-two male GK rats were randomly divided into 2 groups consisting of consistent hish blood glucose group(HG)and intermittent high blood glucose group(FG).Eleven male Wistar rats were used as normal glucose controls(NG).The fluctuating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time for six weeks.Intraperitoneal injection glucose tolerance test and insulin release test were performed.The area under curve of glucose(AUCg).the area under carve of insulin(AUCi)/AUCg and the ratio of insulin increment to blood glucose increment 15 min after glucose load(Δ115'/ΔG15')were calculated routinely.Then the pancreatic slides were stained with insulin antibody.The apoptotic β cells in islets were detected and quantified by the TUNEL technique.Results(1)The fasting plasma glucose and 15,30,60,and 120 min plasma glucose levels after glucose loading in FG group were significantly higher than those in control group(all P<0.01),and AUCg was also markedly increased[(1 012.14±82.62 vs 813.60±56.70)ng·ml~(-1)·h~(-1)·10~4,P<0.01].Insulin levels of FG group at 15,30,60,and 120 rain after glucose loading were significantly lower than those in HG group[(0.554± 0.18 vs 0.95±0.28.0.43±0.17 vs 0.85±0.21,0.47±0.11 vs 0.76±0.16,0.58±0.13 vs 1.08±0.26)ng/ml,P<0.05],along with decreased AUCi/AUCg and Δ115'/ΔG15'[(9.56±2.53 vs 21.36±4.16)×10~(-7);(3.95±3.45 vs 27.02±8.62)×10~(-7),both P<0.05].(2)Image analysis of pancreatic islet immunocytoehemistry showed that the insulin staining positive area,area ratio and total density of insulin positive cells per islet were significantly lower in FG group than those in HG group(P<0.05).(3)The percentage of β-cell apoptosis in the FG group was statistically higher than that in the HG group[(24.17±7.25 vs 16.55±5.11)%,P<0.01].Conclusion Compared with the consistent high blood glucose,intermittent high glucose could lead to further impairment of β-cell function and increased β-cell apoptosis may partially contribute to this process.
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Objective To compare the effects of rat proinsulin gene therapy via intraportal infusion and intramuscular injection blood glucose level in streptozotocin-induced diabetic rots. Methods (1) Recombinant eukaryotic cell expression plasmid of rat proinsulin gene pCMV/proiusulin was transferred into streptozotocin-induced diabetic rats by intraportal infusion and intramuscular injection to observe the effect of rat proiusulin gene therapy in diabetic rats. The treatment group by intraportal infusion (group A) and the group by intramuscular injection (group C) were given pCMV/proinsulin naked plasmid DNA 100 μg, while the control groups by intraportal infusion (group B) or by intramuscular injection (group D) were treated with similar amount of pCMV DNA. Normal group and diabetes mellitus group were also observed at the same time. (2) Blood glucose level was tested and serum insulin was determined by radioimmunoassay. RT-PCR and immunohistochemistry were used to detemine proinsulin mRNA and protein expressions in liver and skeletal muscle and protein. Results (1) The blood glucose levels in two treated groups were both decreased. In group A, levels of blood sugar decreased about 7 mmol/L and glycemie control was maintained for 3-4 weeks. Serum insulin levels step up significantly after pCMV/proinsulin gene therapy. The blood glucose level in group A was significantly lower than those of group B and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). In group C, blood glucose levels decreased about 4 mmol/L and glycemic control was maintained for 1-2 weeks. Meanwhile, the concentrations of insulin increased markedly after gene therapy. The blood glucose in group C was significantly lower than those of group D and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). (2) Proinsulin mRNA and protein expressions could be detected in either hepatic cell of group A or skeletal muscle cell of group C, not in group B and group D. Conclusion Proiusulin genetherapy via intraportal infusion or intramuscular injection lowers significantly blood glucose in diabetic rats, and thus offers a potential approach to treatment of diabetes.
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The intrauterine growth retardation (IUGR) model was established by maternal nutrition restriction during mid- to late-gestation. IUGR rats had both impaired pancreatic development and islet β-cell dysfunction. As the animals grew, the rats gradually showed impaired glucose tolerance and decreased insulin sensitivity.
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Six thousand and forty-four subjects in Jiangsu community were enrolled to investigate the relationship between subclinical thyroid dysfunction and blood pressure. It was shown that subclinical thyroid dysfunction, including both the subclinical hyperthyroidism and subclinical hypothyroidism, had no relationship with increased blood pressure.
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Glycemic excursion was induced in SD rats by intraperitoneal injection of 50% glucose solution, and cells isolated from bone marrow of these rats showed cell clusters which expressed insulin, c-peptide, glucagon, somatostatin and islet amyloid polypeptide, and other genes related to islet-cells development and functions.
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The potential effect of donor CD4+ CD25+ regulatory T ceLls on the suppression of rejection for allogenetic islet transplantation in vivo was investigated. CD4+ CD25+ regulatory T cells were generated by magnetic activated cell sorting and were ailogeneically transfered with islet transplantation in streptozotocin-induced diabetic BALB/cByJ mice. The results showed that allogeneic CD4+ CD25+ regulatory T cells prolong islet graft survival and normoglycemia in transplanted allogeneic diabetic mice.
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Genechip was applied to explore gene expression profile of islets in rats at various stages of pregnancy. Compared with the normal control group, differential expressions of hundreds of genes were detected during pregnancy. Reg3α gene expression was markedly increased during pregnancy, which may be related to islet regeneration.