|
|
||||||||
1Veterans Affairs San Diego Healthcare System; and 2Department of Medicine, University of California, San Diego, California
Submitted 12 April 2006 ; accepted in final form 30 May 2006
Glycogen synthase kinase-3 (GSK-3) is a ubiquitous kinase implicated in both insulin action and adipogenesis. To determine how these multiple roles may relate to insulin resistance, we studied the regulation of GSK-3 protein expression and phosphorylation in skeletal muscle and isolated adipocytes from nonobese healthy control (HC), obese control (OC), and obese type 2 diabetic (OT2D) subjects. At baseline there were no differences in the GSK-3 protein expression in adipocytes. OC subjects underwent a 6-mo caloric restriction resulting in a 7% decrease in body mass index (BMI) and a 21% improvement in insulin-stimulated whole body glucose disposal rate (GDR). GSK-3
and GSK-3
expression decreased in adipocytes (P < 0.05), whereas GSK-3
protein expression increased in skeletal muscle (P < 0.05). OT2D subjects were treated with troglitazone or metformin for 34 mo. After troglitazone treatment GDR improved (P < 0.05) despite an increase in BMI (P < 0.05), whereas metformin had no significant effect on GDR. There was no significant change in GSK-3 expression in adipocytes following troglitazone, whereas both GSK-3
and -
were decreased in skeletal muscle (P < 0.05). Metformin treatment had no significant impact on GSK-3 protein expression in either adipocytes or skeletal muscle. Neither treatment influenced GSK-3 serine phosphorylation in skeletal muscle or adipocytes. These results suggest that there is tissue specificity for the regulation of GSK-3 in humans. In skeletal muscle GSK-3 plays a role in control of metabolism and insulin action, whereas the function in adipose tissue is less clear.
glycogen synthase kinase-3; weight loss; thiazolidinedione; type 2 diabetes mellitus; metabolism; insulin action
This article has been cited by other articles:
![]() |
Y. Zheng, W. Zhang, E. Pendleton, S. Leng, J. Wu, R. Chen, and X. J. Sun Improved insulin sensitivity by calorie restriction is associated with reduction of ERK and p70S6K activities in the liver of obese Zucker rats J. Endocrinol., December 1, 2009; 203(3): 337 - 347. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R Soeters, N. M Lammers, P. F Dubbelhuis, M. Ackermans, C. F Jonkers-Schuitema, E. Fliers, H. P Sauerwein, J. M Aerts, and M. J Serlie Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1244 - 1251. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Phillips, J. Kung, T. P. Ciaraldi, C. Choe, L. Christiansen, S. Mudaliar, and R. R. Henry Selective regulation of cellular and secreted multimeric adiponectin by antidiabetic therapies in humans Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E767 - E773. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Phillips, T. P. Ciaraldi, Deborah. K. Oh, M. K. Savu, and R. R. Henry Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E842 - E850. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Liberman, B. Plotkin, T. Tennenbaum, and H. Eldar-Finkelman Coordinated phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 and protein kinase C{beta}II in the diabetic fat tissue Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1169 - E1177. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. D. Folmes, L. A. Witters, M. F. Allard, M. E. Young, and J. R. B. Dyck The AMPK {gamma}1 R70Q mutant regulates multiple metabolic and growth pathways in neonatal cardiac myocytes Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3456 - H3464. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |