Rosiglitazone, Insulin Treatment, and Fasting Correct Defective Activation of Protein Kinase C-[zeta]/[lambda] by Insulin in Vastus Lateralis Muscles and Adipocytes of Diabetic Rats*.
Kanoh, Yoshinori; Bandyopadhyay, Gautam; Sajan, Mini P; Standaert, Mary L; Farese, Robert V
[Miscellaneous Article] Endocrinology. 142(4):1595-1605, April 2001.

(Format: HTML, PDF)

Atypical protein kinases C (PKCs), [zeta] and [lambda], and protein kinase B (PKB) are thought to function downstream of phosphatidylinositol 3-kinase (PI 3-kinase) and regulate glucose transport during insulin action in skeletal muscle and adipocytes. Insulin-stimulated glucose transport is defective in type II diabetes mellitus, and this defect is ameliorated by thiazolidinediones and lowering of blood glucose by chronic insulin therapy or short-term fasting. Presently, we evaluated the effects of these insulin-sensitizing modalities on the activation of insulin receptor substrate-1 (IRS-1)-dependent PI 3-kinase, PKC-[zeta]/[lambda], and PKB in vastus lateralis skeletal muscles and adipocytes of nondiabetic and Goto-Kakizaki (GK) diabetic rats. Insulin provoked rapid increases in the activity of PI 3-kinase, PKC-[zeta]/[lambda], and PKB in muscles and adipocytes of nondiabetic rats, but increases in IRS-1-dependent PI 3-kinase and PKC-[zeta]/[lambda], but not PKB, activity were substantially diminished in GK muscles and adipocytes. Rosiglitazone treatment for 10-14 days, 10-day insulin treatment, and 60-h fasting reversed defects in PKC-[zeta]/[lambda] activation in GK muscles and adipocytes and increased glucose transport in GK adipocytes, without necessarily increasing IRS-1-dependent PI 3-kinase or PKB activation. Our findings suggest that insulin-sensitizing modalities, viz. thiazolidinediones, chronic insulin treatment, and short-term fasting, similarly improve defects in insulin-stimulated glucose transport at least partly by correcting defects in insulin-induced activation of PKC-[zeta]/[lambda].

Copyright (C) 2001 by The Endocrine Society