1型糖尿病小鼠肝脏的口服葡萄糖代谢及差异表达基因

目的：观察口服葡萄糖在1型糖尿病小鼠肝脏的代谢,比较1型糖尿病小鼠与正常小鼠口服葡萄糖后肝组织基因表达的差异。方法：链脲霉素（STZ）诱导C57雄性小鼠1型糖尿病模型为实验组（n=8）,正常C57雄性小鼠为对照组（n=8）。每组随机取2只,按50ml／kg给予4％葡萄糖生理盐水溶液灌胃,2h取肝组织检测基因表达谱（Mouse Genome 430 2．0Array）。每组另6只．同样剂量给予含14C标记葡萄糖。结果：糖尿病小鼠口服14C标记葡萄糖2h后,肝组织同位素水平是正常对照组的4倍。以正常对照组为参比,共有舛条基因的表达变化差异在2倍以上,其中上调基因61个,下调基因33个。根据功能基因组分析,11条差异表达基因与脂代谢、胆固醇代谢相关,其中7条上调基因与脂、胆固醇合成相关,1条下调基因与脂肪酸分解相关。结论：SIZ诱导的1型糖尿病小鼠口服葡糖后2h,肝脏脂、胆固醇合成相关基因表达增高。     

Pollen Typhae total flavone improves insulin resistance in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats

Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, is reported to enhance glucose uptake in C2C12 myotubes in vitro, but the convincing evidence is lacking in vivo. In this study, PTF ameliorated insulin resistance and dyslipidemia, but failed to significantly increase body weight in type 2 diabetic rats induced by high-fat diet and low-dose streptozotocin.     

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats

This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 ± 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 ± 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 ± 1.28×10⁻⁸ μmol/mg/min) was significantly higher than that in the diabetic rats (1.26 ± 0.35×10⁻⁸; p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.     

Transplantation of human umbilical cord blood cells improves glycemia and glomerular hypertrophy in type 2 diabetic mice

Recent in vitro and in vivo studies have shown that either animal- or human-derived embryonic stem cells can differentiate into insulin-secreting cells and lower blood glucose levels. However, studies utilizing human umbilical cord blood (HUCB) mononuclear cells to improve blood glucose levels in diabetic animals have received little attention. In this study, we examined the effect of transplanted HUCB mononuclear cells on blood glucose levels, survival, and renal pathology in obese mice with spontaneous development of type 2 diabetes. The results show that injection of HUCB mononuclear cells into orbital plexus of mice caused improvement not only in blood glucose levels and survival rate but also normalization of glomerular hypertrophy and tubular dilatation. Thus, transplantation of HUCB mononuclear cells appears to be another modality of stem cell therapy in diabetes mellitus.     

Effect of Lactobacillus gasseri BNR17 on blood glucose levels and body weight in a mouse model of type 2 diabetes

Aims:  To investigate the effect of Lactobacillus gasseri BNR17 isolated from human breast milk on blood glucose and body weight in type 2 diabetic animals.
Methods and results:  db/db mice were divided into one control group and five sample groups; the sample groups received BNR17 (10⁷, 10⁸, 10⁹ and 10¹⁰ CFU) or rosiglitazone (8 mg kg⁻¹) orally twice a day for 12 weeks. BNR17 groups had a dose-dependent reduction in food, water intake and amount of excrement. Body weight loss was not seen in the BNR17 groups. Fasting and postprandial 2 h blood glucose levels were significantly lower in the BNR17 (10¹⁰ CFU) group compared with the control group. HbA1c decreased in the BNR17 group, although it was not statistically significant. During the oral glucose tolerance test, the BNR17 groups exhibited dose-dependent improvement in glucose sensitivity.
Conclusions:  Lactobacillus gasseri BNR17 has a suppressing effect on blood glucose levels and improved diabetic symptoms in db/db mice.
Significance and Impact of the Study:  Blood glucose-lowering lactic acid bacteria are expected to be useful as a therapeutic for treating type 2 diabetes in humans.     

Differential modulation of white adipose tissue endocannabinoid levels by n-3 fatty acids in obese mice and type 2 diabetic patients

n-3 polyunsaturated fatty acids (n-3 PUFA) might regulate metabolism by lowering endocannabinoid levels. We examined time-dependent changes in adipose tissue levels of endocannabinoids as well as in parameters of glucose homeostasis induced by n-3 PUFA in dietary-obese mice, and compared these results with the effect of n-3 PUFA intervention in type 2 diabetic (T2DM) subjects. Male C57BL/6J mice were fed for 8, 16 or 24?weeks a high-fat diet alone (cHF) or supplemented with n-3 PUFA (cHF?+?F). Overweight/obese, T2DM patients on metformin therapy were given for 24?weeks corn oil (Placebo; 5?g/day) or n-3 PUFA concentrate as above (Omega-3; 5?g/day). Endocannabinoids were measured by liquid chromatography-tandem mass-spectrometry. Compared to cHF-fed controls, the cHF?+?F mice consistently reduced 2-arachidonoylglycerol (up to ~2-fold at week 24) and anandamide (~2-fold) in adipose tissue, while the levels of endocannabinoid-related anti-inflammatory molecules N-eicosapentaenoyl ethanolamine (EPEA) and N-docosahexaenoyl ethanolamine (DHEA) increased more than ~10-fold and ~8-fold, respectively. At week 24, the cHF?+?F mice improved glucose tolerance and fasting blood glucose, the latter being positively correlated with adipose 2-arachidonoylglycerol levels only in obese cHF-fed controls, like fasting insulin and HOMA-IR. In the patients, n-3 PUFA failed to reduce 2-arachidonoylglycerol and anandamide levels in adipose tissue and serum, but they increased both adipose tissue and serum levels of EPEA and DHEA. In conclusion, the inability of n-3 PUFA to reduce adipose tissue and serum levels of classical endocannabinoids might contribute to a lack of beneficial effects of these lipids on glucose homeostasis in T2DM patients.