Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to est...Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin （STZ）-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor （TNF）-α, interleukin-1β （IL-1β） and interleukin-6 （IL-6）. Methods Twenty-two male Chinese Guizhou minipigs （age, 4 to 6 months; weight, 20 kg to 30 kg） were divided into STZ-induced diabetic group （n=-12） and control group （n=-10）. STZ （125 mg/kg） was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test （OGTT） was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparegine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet 13 cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-β and IL-6 mFINA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction （FIT-PCR）. Results Significant elevation in serum glucose levels was observed one month and six months after STZ induction （P〈0.001） and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β ceils almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Westem blot demonstrated dramatica展开更多
objective： To investigate the effect of Jiaotai Pill （交泰丸, JTP） at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase （PI3K） pathway in the skeletal muscle of diabe...objective： To investigate the effect of Jiaotai Pill （交泰丸, JTP） at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase （PI3K） pathway in the skeletal muscle of diabetic rats. Methods： The rat model of type 2 diabetes mellitus （T2DM） was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method. Results： All the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β （InsR β） subunit, insulin receptor substrate-1 （IRS-1）, PI3K p85 subunit and glucose transporter 4 （GLUT4） in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect. Conclusion： JTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.展开更多
基金The study was supported by the grant from the Shanghai Natural Science Foundation(No.028610)
文摘Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin （STZ）-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor （TNF）-α, interleukin-1β （IL-1β） and interleukin-6 （IL-6）. Methods Twenty-two male Chinese Guizhou minipigs （age, 4 to 6 months; weight, 20 kg to 30 kg） were divided into STZ-induced diabetic group （n=-12） and control group （n=-10）. STZ （125 mg/kg） was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test （OGTT） was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparegine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet 13 cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-β and IL-6 mFINA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction （FIT-PCR）. Results Significant elevation in serum glucose levels was observed one month and six months after STZ induction （P〈0.001） and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β ceils almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Westem blot demonstrated dramatica
基金Supported by grants from National Natural Science Foundation of China(No.30801492)
文摘objective： To investigate the effect of Jiaotai Pill （交泰丸, JTP） at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase （PI3K） pathway in the skeletal muscle of diabetic rats. Methods： The rat model of type 2 diabetes mellitus （T2DM） was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method. Results： All the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β （InsR β） subunit, insulin receptor substrate-1 （IRS-1）, PI3K p85 subunit and glucose transporter 4 （GLUT4） in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect. Conclusion： JTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.
