Sirtuin 3 is involved in the regulation of glucose stimulated insulin secretion (GSIS)
Other conference paper


摘要Purpose of the study
Impairment of GSIS, a hallmark of type 2 diabetes, can be induced by a series of pathological conditions such as hyperglycemia and hyperlipidemia. Normal pancreatic beta cell mitochondrial function is essential for GSIS. Sirt3 is a mitochondrial deacetylase which regulates a series of cell metabolic pathways including glucose metabolism and fatty acid oxidation. We aimed to investigate the role of Sirt3 in the regulation of GSIS in pancreatic beta cells.

We generated pancreatic beta cell specific Sirt3 knockout (Sirt3βKO) mice to compare the glycemic responses in wild type (WT) mice using Ins1 (insulin)-promoter driven Cre-mediated deletion of floxed Sirt3 allele. Both Sirt3βKO and wild type (WT) mice were fed with high fat diet (HFD, 60Êl fat) and standard diet (STD) for 28 weeks. Fasting blood glucose (FBG) and body weight were measured every 4 weeks. Oral glucose tolerance test (OGTT) and insulin level were measured after the mice became diabetic (FBG of HFD mice were above 7 mmol/l).

Summary of the results
We first confirmed specific deletion by showing diminished SIRT3 protein expression in β cells but no decrease in other tissues including liver, lung, heart, etc., in Sirt3βKO. Both Sirt3βKO and Sirt3βWT littermates were fed with HFD for 28 weeks to generate diabetic mice with impaired insulin secretion. The FBG and body weight of HFD mice, rather than STD mice rose steadily during these time periods. Mice from WT+HFD group appeared high FBG level (> 7 mmol/l) at 16th week, 4 weeks earlier than Sirt3βKO+HFD group. However, after 16th week, Sirt3βKO+HFD group started to catch up and even ascended faster than WT+HFD group. FBG levels were similar in normal chow fed mice of both groups. More importantly, glucose tolerance was further impaired in HFD fed Sirt3βKO mice than HFD fed WT mice. Insulin levels measured during OGTT showed that impairment of GSIS was exacerbated worse in HFD fed Sirt3βKO mice than HFD fed WT. In addition, the insulin peak of Sirt3βKO+HFD mice appeared to be delayed than WT+HFD mice. Further mechanistic studies are in progress to examine how SIRT3 inhibition impaired insulin secretion/production in β cells.

Sirt3 plays an important role in pancreatic beta cell GSIS under oxidative stress in the context of type 2 diabetes.
著者Ming X, Tian XY, Chung CK, Lee HM, Cao HY, Chan CN, Kong PS
會議名稱East meets west symposium 2018
會議地點Hong Kong

上次更新時間 2020-28-04 於 16:50