Insulin receptor activation inhibits insulin secretion from human islets of Langerhans

FEBS Letters

Persaud, Shanta J¹  Asare-Anane, Henry¹  Jones, Peter M¹ 

[1] Endocrinology and Reproduction Research Group, GKT School of Biomedical Sciences, Room 3.2A, New Hunt's House, King's College London, London SE1 1UL, UK

关键词: Human islet of Langerhans;    Insulin secretion;    Autocrine;    Perifusion;    IRS;    insulin receptor substrate;    PI 3-kinase;    phosphatidylinositol 3-kinase;   

DOI  :  10.1016/S0014-5793(01)03268-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

There is no consensus on the role of insulin secreted from pancreatic β-cells in regulating its own secretion, either in rodent islets or in human islets. We have now investigated whether there is an autocrine signalling role for insulin in human islets by determining insulin receptor expression and assessing the effects of insulin receptor activation using a non-peptidyl insulin mimetic termed L-783,281. Human insulin receptor mRNA was detected by PCR amplification of human islet cDNA, and translation of the message in human islets was confirmed by Western blotting. Perifusion experiments revealed that both glucose-stimulated and basal insulin secretion were significantly inhibited following human islet insulin receptor activation with L-783,281, and that signalling through phosphatidylinositol 3-kinase (PI 3-kinase) was responsible, at least in part, for this inhibitory effect. These studies indicate that human islets express insulin receptors and that they are functionally coupled to a PI 3-kinase-dependent inhibition of insulin secretion.

【 授权许可】

Unknown