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Insulin receptor activation inhibits insulin secretion from human islets of Langerhans
Author(s) -
Persaud Shanta J,
Asare-Anane Henry,
Jones Peter M
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03268-9
Subject(s) - insulin , insulin receptor , islet , insulin receptor substrate , endocrinology , medicine , insulin oscillation , autocrine signalling , biology , irs2 , grb10 , receptor , insulin resistance
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.