RESUMO
In diabetes mellitus, pituitary adenylate cyclase-activating polypeptide (PACAP) has insulinotropic and glucose-lowering properties. We previously demonstrated that transgenic mice overexpressing PACAP in pancreatic ß-cells (PACAP-Tg) show attenuated pancreatic islet hyperplasia and hyperinsulinemia in type 2 diabetic models. To explore the underlying mechanisms, here we crossed PACAP-Tg mice with lethal yellow agouti (KKAy) diabetic mice, and performed gene chip analysis of laser capture microdissected pancreatic islets from four F1 offspring genotypes (wild-type, PACAP-Tg, KKAy, and PACAP-Tg:KKAy). We identified 1371 probes with >16-fold differences between at least one pair of genotypes, and classified the probes into five clusters with characteristic expression patterns. Gene ontology enrichment analysis showed that genes involved in the terms ribosome and intracellular organelles such as ribonucleoprotein complex, mitochondrion, and chromosome organization were significantly enriched in clusters characterized by up-regulated genes in PACAP-Tg:KKAy mice compared with KKAy mice. These results may provide insight into the mechanisms of diabetes that accompany islet hyperplasia and amelioration by PACAP.
RESUMO
Objective To detect the expression of FoxO3a in adipose tissue from KKay diabetic mice and the effects of treatment with rosiglitazone and metformin on FoxO3a expression in adipose tissue in order to understand the mechanism of insulin resistance.Methods Mice were randomly divided into 3 groups: the group without any treatment,group with rosiglitazone and group treated with metformin 3 g/kg/day.Control group consists of 7 C57BL mice 16.Dispatched the mice and sampled adipose tissue to measure the protein concentration by Bradford method and to detect Foxo3a protein expression on adipose tissue by Western Blot with multiple colony antibody 1∶1250.Results Foxo3a was highly expressed in adipose from KKAy diabetic mice as compared with that in control group(FoxO3a/?-actin ratio 1.76?0.19 vs 1.15?0.10,P
RESUMO
Objective To detect the expression of FoxO1 and FoxO3a in liver and muscle tissue from KKAy diabetic mice.Methods Study group consists of 7 KKAy diabetic mice until 12 weeks,thereafter fed high fat diet for 4 weeks.It was diagnosed as diabetes when blood glucose was more than(16.7 mmol/L) in two consequent weeks.Control group consists of 7 C57BL mice 16 week old.Dispatched the mice and took quadriceps of femoris muscle and liver tissue to detect the FoxO1 and FoxO3a protein expression by Western blot with antibody.Results Liver and muscle FoxO1 expression was higher in KKAy diabetic mice than that in C57BL mice.FoxO3a expression was much higher in liver than in muscle in both groups.Muscle FoxO3a expression was higher in KKAy diabetic mice than that in control mice.Conclusion FoxO1 and FoxO3a in liver and muscle expressed differently in diabetic mice and control mice.They may play a role in mechanisms of insulin resistance and type 2 diabetes mellitus.
RESUMO
Objective: To investigate the effects of green tea polysaccharides (TPs) on glucose metabolism and the activity of peroxisome proliferator-activated receptor gamma (PPAR-?) in KKAy type 2 diabetic mice. Methods: Glucose tolerance test, fasting and postprandial glucose, gluconeogenesis, and insulin sensitivity were investigated in type 2 diabetic mice with orally administered TPs at the dose of 500mg/kg for 4-10 w. Effect of TPs on activity of PPAR-? was tested in vitro. Results: TPs could not only improve glucose tolerance, but also reduce fasting and postprandial blood glucose. In addition, TPs could inhibit gluconeogenesis and enhance insulin sensitivity in KKAy diabetic mice. TPs had also an effect of activating of PPAR-? with dose-response. Conclusion: TPs have beneficial effect of lowering blood glucose in KKAy type 2 diabetic mice, which may be induced by enhancing insulin sensitivity by activating of PPAR-?.
