Okadaic Acid Exerts a Full Insulin-like Effect on Glucose Transport and Glucose Transporter 4 Translocation in Human Adipocytes

doi:10.1074/jbc.271.30.18148

Okadaic Acid Exerts a Full Insulin-like Effect on Glucose Transport and Glucose Transporter 4 Translocation in Human Adipocytes

EVIDENCE FOR A PHOSPHATIDYLINOSITOL 3-KINASE-INDEPENDENT PATHWAY*

Cristina M. Rondinone^‡ and
Ulf Smith

From the Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, University of Goteborg, S-413 45 Goteborg, Sweden

^‡ To whom correspondence should be addressed. Tel.: 46-31-601104; Fax: 46-31-825330; E-mail: cristina.rondinone{at}medicine.gu.se.

Abstract

The effects of the serine/threonine phosphatase inhibitor, okadaic acid, and insulin on glucose transport activity, glucose transporter 4 translocation to the plasma membrane, and the signaling pathway of insulin were examined in human adipocytes. Okadaic acid consistently produced a greater increase than insulin in the rate of glucose transport, and both agents together had a partial additive effect. Both insulin alone and okadaic acid alone stimulated the translocation of glucose transporter 4 to the plasma membrane. Insulin, but not okadaic acid, stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity, and wortmannin completely inhibited the effect of insulin on glucose transport. When the cells were incubated with both agents, okadaic acid inhibited insulin-stimulated PI 3-kinase activity but did not block the association of the p85 or p110 subunits of PI 3-kinase with insulin receptor substrate 1. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 was only slightly reduced (15-30%) by okadaic acid. These data demonstrate that okadaic acid exerts a full insulin-like effect independent of the activation of PI 3-kinase. Thus, PI 3-kinase lipid kinase is not essential for glucose transporter 4 translocation in human adipocytes, and different pathways exist that lead to glucose transporter 4 translocation and increased glucose transport.

Footnotes

↵* This work was supported by grants from the Swedish Medical Research Council (B-3506) and the IngaBritt and Arne Lundberg Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

GLUT

glucose transporter

IRS-1

insulin receptor substrate

PI

phosphatidylinositol

BSA

bovine serum albumin

SDS

sodium dodecyl sulfate

PAGE

polyacrylamide gel electrophoresis.
- Received November 22, 1995.
- Revision received April 24, 1996.