Excess exposure to insulin (glargine) induces type 2 diabetes mellitus in mice on chow diet. The Journal of Endocrinology. Apr 16, 2014 [Epub ahead of print] Yang X1, Mei S, Gu H, Guo H, Zha L, Cai J, Li X, Liu Z, Cao W.
1X Yang, Nutrition, UNC at Chapel Hill, Kannapolis, United States.
We have previously shown that insulin plays an essential role in nutrients-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical T2DM in normal mice on chow diet. C57BL/6 mice were treated with long-acting insulin (glargine) once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and mitochondrial content of cholesterol in tissues. Mitochondrial content of cholesterol and its association with oxidative stress in cultured hepatocytes and beta cells were also examined. Results show that chronic exposure to insulin caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess insulin led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased mitochondrial content of cholesterol in liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce T2DM in normal mice on chow diet.
PMID: 24741073 [PubMed – as supplied by publisher]