Insulin signalling in islets

Biochem Soc Trans. 2008 Jun;36(Pt 3):290-3. doi: 10.1042/BST0360290.

Abstract

Studies in transgenic animals, rodent insulin-secreting cell lines and rodent islets suggest that insulin acts in an autocrine manner to regulate beta-cell mass and gene expression. Very little is known about the in vitro roles played by insulin in human islets, and the regulatory role of insulin in protecting against beta-cell apoptosis. We have identified mRNAs encoding IRs (insulin receptors) and downstream signalling elements in dissociated human islet beta-cells by single-cell RT (reverse transcription)-PCR, and perifusion studies have indicated that insulin does not have an autocrine role to regulate insulin secretion from human islets, but activation of the closely related IGF-1 (insulin-like growth factor 1) receptors is linked to inhibition of insulin secretion. Knockdown of IR mRNA by siRNAs (small interfering RNAs) decreased IR protein expression without affecting IGF-1 receptor levels, and blocked glucose stimulation of preproinsulin gene expression. Similar results were obtained when human islet IRS (IR substrate)-2 was knocked down, whereas depletion of IRS-1 caused an increase in preproinsulin mRNA levels. Studies using the mouse MIN6 beta-cell line indicated that glucose protected beta-cells from undergoing apoptosis and that this was a consequence, at least in part, of insulin release in response to elevated glucose. IGF-1 also exerted anti-apoptotic effects. These data indicate that insulin can exert autocrine effects in human islets through receptors on beta-cells. It protects beta-cells against apoptosis and increases preproinsulin mRNA synthesis, but does not affect insulin secretion.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis / drug effects
  • Autocrine Communication / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Insulin Receptor Substrate Proteins
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Signal Transduction* / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptor, Insulin