Identification of insulin signaling elements in human beta-cells - Autocrine regulation of insulin gene expression

TY - JOUR

T1 - Identification of insulin signaling elements in human beta-cells - Autocrine regulation of insulin gene expression

AU - Muller, D

AU - Huang, G C

AU - Amiel, S

AU - Jones, P M

AU - Persaud, S J

PY - 2006/10

Y1 - 2006/10

N2 - 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 p110 alpha, p110 beta, PI3KC2 alpha, and PI3KC2 gamma; phosphoinositide-dependent protein kinase-1; protein kinase B (PKB)alpha, PKBR, and PKB gamma 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

AB - 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 p110 alpha, p110 beta, PI3KC2 alpha, and PI3KC2 gamma; phosphoinositide-dependent protein kinase-1; protein kinase B (PKB)alpha, PKBR, and PKB gamma 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

U2 - 10.2337/db06-0532

DO - 10.2337/db06-0532

M3 - Article

VL - 55

SP - 2835

EP - 2842

JO - Diabetes

JF - Diabetes

IS - 10

ER -