Function and dysfunction of aPKC isoforms for glucose transport in insulin-sensitive and insulin-resistant states

Abstract

Considerable evidence suggests that atypical protein kinase C isoforms (aPKCs), serving downstream of insulin receptor substrates and phosphatidylinositol (PI) 3-kinase, are required for insulin-stimulated glucose transport in skeletal muscle and adipocytes. More recent findings further suggest that aPKCs are activated and required for glucose transport responses while serving downstream of 1) proline-rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase D, as during the actions of high concentrations of carbohydrates (glucose, sorbitol) and agents that activate 5′-AMP-activated protein kinase (exercise, 5-amino-imidazole-4-carboxamide-1-β-d-riboside, dinitrophenol), and 2) Cbl-dependent PI 3-kinase, as during the action of insulin-sensitizing thiazolidinediones. It therefore seems reasonable to postulate that, regardless of the initial mechanism, aPKCs may serve as terminal molecular switches for activating glucose transport responses. This postulation is of critical importance, as it now appears that insulin-stimulated aPKC activation is compromised in various states of insulin resistance.