期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 29, 期 11, 页码 3219-3228出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01489-08
关键词
-
资金
- NIH [RO1 DK 67536, RO1 DK 68721]
- DERC [P30 DK36836]
Insulin and insulin-like growth factor I (IGF-I) are ubiquitous hormones that regulate growth and metabolism of most mammalian cells, including pancreatic beta-cells. In addition to being an insulin secretagogue, glucose regulates proliferation and survival of beta-cells. However, it is unclear whether the latter effects of glucose occur secondary to autocrine activation of insulin signaling proteins by secreted insulin. To examine this possibility we studied the effects of exogenous glucose or insulin in beta-cell lines completely lacking either insulin receptors (beta IRKO) or insulin receptor substrate 2 (beta IRS2KO). Exogenous addition of either insulin or glucose activated proteins in the insulin signaling pathway in control beta-cell lines with the effects of insulin peaking earlier than glucose. Insulin stimulation of beta IRKO and beta IRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase. Control beta-cells exhibited low expression of IGF-1 receptors compared to compensatory upregulation in beta IRKO cells. The signaling data support the slow growth and reduced DNA and protein synthesis in beta IRKO and beta IRS2KO cells in response to glucose stimulation. Together, these studies provide compelling evidence that the growth and survival effects of glucose on beta-cells require activation of proteins in the insulin signaling pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据