Studies in transgenic animals, rodent insulin-secreting cell lines and rodent islets suggest that insulin acts in an autocrine manner to regulate β-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 β-cell apoptosis. We have identified mRNAs encoding IRs (insulin receptors) and downstream signalling elements in dissociated human islet β-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 β-cell line indicated that glucose protected β-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 β-cells. It protects β-cells against apoptosis and increases preproinsulin mRNA synthesis, but does not affect insulin secretion.
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June 2008
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Conference Article|
May 21 2008
Insulin signalling in islets
Shanta J. Persaud;
Shanta J. Persaud
1
1Beta Cell Development & Function Group, King's College London, London, U.K.
1To whom correspondence should be addressed (email shanta.persaud@kcl.ac.uk).
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Dany Muller;
Dany Muller
1Beta Cell Development & Function Group, King's College London, London, U.K.
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Peter M. Jones
Peter M. Jones
1Beta Cell Development & Function Group, King's College London, London, U.K.
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Biochem Soc Trans (2008) 36 (3): 290–293.
Article history
Received:
November 09 2007
Citation
Shanta J. Persaud, Dany Muller, Peter M. Jones; Insulin signalling in islets. Biochem Soc Trans 1 June 2008; 36 (3): 290–293. doi: https://doi.org/10.1042/BST0360290
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