Identification of insulin signaling elements in human beta-cells: autocrine regulation of insulin gene expression.

Abstract:

:Although many studies using rodent islets and insulinoma cell lines have been performed to determine the role of insulin in the regulation of islet function, the autocrine effect of insulin on insulin gene expression is still controversial, and no consensus has yet been achieved. Because very little is known about the insulin signaling pathway in human islets, we used single-cell RT-PCR to profile the expression of genes potentially involved in the insulin signaling cascade in human beta-cells. The detection of mRNAs for insulin receptor (IR)A and IRB; insulin receptor substrate (IRS)-1 and IRS-2; phosphoinositide 3-kinase (PI3K) catalytic subunits p110alpha, p110beta, PI3KC2alpha, and PI3KC2gamma; phosphoinositide-dependent protein kinase-1; protein kinase B (PKB)alpha, PKBbeta, and PKBgamma in the beta-cell population suggests the presence of a functional insulin signaling cascade in human beta-cells. Small interfering RNA-induced reductions in IR expression in human islets completely suppressed glucose-stimulated insulin gene expression, suggesting that insulin regulates its own gene expression in human beta-cells. Defects in this regulation may accentuate the metabolic dysfunction associated with type 2 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Muller D,Huang GC,Amiel S,Jones PM,Persaud SJ

doi

10.2337/db06-0532

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

2835-42

issue

10

eissn

0012-1797

issn

1939-327X

pii

55/10/2835

journal_volume

55

pub_type

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