AJP - Endo Cosmo Bio: Excellent Endocrine ELISAs
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab (January 25, 2005). doi:10.1152/ajpendo.00547.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/6/E1188    most recent
00547.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dokken, B. B.
Right arrow Articles by Henriksen, E. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dokken, B. B.
Right arrow Articles by Henriksen, E. J.
Submitted on November 12, 2004
Accepted on January 21, 2005

Acute Selective Glycogen Synthase Kinase-3 Inhibition Enhances Insulin Signaling in Pre-Diabetic Insulin-Resistant Rat Skeletal Muscle

Betsy B. Dokken1, Julie A. Sloniger1, and Erik J. Henriksen1*

1 Department of Physiology, University of Arizona, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: ejhenrik{at}u.arizona.edu.

Glycogen synthase kinase-3 (GSK3) has been implicated in the multifactorial etiology of skeletal muscle insulin resistance in animal models and in human type 2 diabetic subjects. However, the potential molecular mechanisms involved are not yet fully understood. Therefore, we determined if selective GSK3 inhibition in vitro leads to an improvement in insulin action on glucose transport activity in isolated skeletal muscle of insulin-resistant, pre-diabetic obese Zucker rats, and if these effects of GSK3 inhibition are associated with enhanced insulin signaling. Type I soleus and type IIb epitrochlearis muscles from female obese Zucker rats were incubated in the absence or presence of a selective, small organic GSK3 inhibitor (1 µM CT118637, Ki<10 nM for GSK3{alpha} and GSK3{beta}). Maximal insulin stimulation (5 mU/ml) of glucose transport activity, glycogen synthase activity, and select insulin signaling factors (tyrosine phosphorylation of insulin receptor (IR) and IRS-1, IRS-1 associated with p85 subunit of phosphatidylinositol-3-kinase, and serine phosphorylation of Akt and GSK3) were assessed. GSK3 inhibition enhanced (P <0.05) basal glycogen synthase activity and insulin-stimulated glucose transport in obese epitrochlearis (81% and 24%) and soleus (108% and 20%) muscles. GSK3 inhibition did not modify insulin-stimulated tyrosine phosphorylation of IR {beta}-subunit in either muscle type. However, in obese soleus, GSK3 inhibition enhanced (all P<0.05) insulin-stimulated IRS-1 tyrosine phosphorylation (45%), IRS-1 associated p85 (72%), Akt1/2 serine phosphorylation (30%), and GSK3{beta} serine phosphorylation (39%). Substantially smaller GSK3 inhibitor-mediated enhancements of insulin action on these insulin signaling factors were observed in obese epitrochlearis. These results indicate that selective GSK3 inhibition enhances insulin action in insulin-resistant skeletal muscle of the pre-diabetic obese Zucker rat, at least in part by relieving the deleterious effects of GSK3 action on post- IR insulin signaling. These effects of GSK3 inhibition on insulin action are greater in type I muscle than in type IIb muscle from these insulin-resistant animals.




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
S. Patel, B. W. Doble, K. MacAulay, E. M. Sinclair, D. J. Drucker, and J. R. Woodgett
Tissue-Specific Role of Glycogen Synthase Kinase 3{beta} in Glucose Homeostasis and Insulin Action
Mol. Cell. Biol., October 15, 2008; 28(20): 6314 - 6328.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. A. Gupte, G. L. Bomhoff, and P. C. Geiger
Age-related differences in skeletal muscle insulin signaling: the role of stress kinases and heat shock proteins
J Appl Physiol, September 1, 2008; 105(3): 839 - 848.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. J. Henriksen, M. K. Teachey, K. A. Lindborg, C. J. Diehl, and A. N. Beneze
The high-fat-fed lean Zucker rat: a spontaneous isocaloric model of fat-induced insulin resistance associated with muscle GSK-3 overactivity
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1813 - R1821.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. B. Dokken, V. Saengsirisuwan, J. S. Kim, M. K. Teachey, and E. J. Henriksen
Oxidative stress-induced insulin resistance in rat skeletal muscle: role of glycogen synthase kinase-3
Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E615 - E621.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
G. F. Anhe, S. M. Hirabara, T. C. Turrer, L. C. Caperuto, F. F. Anhe, L. M. Ribeiro, A. C. Marcal, C. R. O. Carvalho, R. Curi, U. F. Machado, et al.
Postpartum glycemic homeostasis in early lactating rats is accompanied by transient and specific increase of soleus insulin response through IRS2/AKT pathway
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2225 - R2233.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. P. Ciaraldi, D. K. Oh, L. Christiansen, S. E. Nikoulina, A. P. S. Kong, S. Baxi, S. Mudaliar, and R. R. Henry
Tissue-specific expression and regulation of GSK-3 in human skeletal muscle and adipose tissue
Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E891 - E898.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. B. Dokken and E. J. Henriksen
Chronic selective glycogen synthase kinase-3 inhibition enhances glucose disposal and muscle insulin action in prediabetic obese Zucker rats
Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E207 - E213.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.