Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Caruso, M.
Right arrow Articles by Beguinot, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Caruso, M.
Right arrow Articles by Beguinot, F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes, Vol 49, Issue 7 1194-1202, Copyright © 2000 by American Diabetes Association

ARTICLES

The IR1152 mutant insulin receptor selectively impairs insulin action in skeletal muscle but not in liver

M Caruso, C Miele, A Oliva, G Condorelli, F Oriente, G Riccardi, B Capaldo, F Fiory, D Accili, P Formisano and F Beguinot
Dipartimento di Biologia e Patologia Cellulare e Molecolare & Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Federico II University of Naples Medical School, Italy.

In patients harboring the IR1152 mutant insulin receptor, hepatic glucose production was normally suppressed by insulin. Hepatocytes without the insulin receptor gene and expressing IR1152 (Hep(MUT)) also showed normal insulin suppression of glucose production and full insulin response of glycogen synthase. In contrast, expression of the IR1152 mutant in skeletal muscle maximally increased glucose uptake and storage, preventing further insulin stimulation. IRS-1 phosphorylation was normally stimulated by insulin in both intact Hep(MUT) and L6 skeletal muscle cells expressing the IR1152 mutant (L6(MUT)). At variance, IRS-2 phosphorylation exhibited high basal levels with no further insulin-dependent increase in L6(MUT) but almost normal phosphorylation, both basal and insulin-stimulated, in the Hep(MUT) cells. In vitro, IR1152 mutant preparations from both the L6(MUT) and the Hep(MUT) cells exhibited increased basal and no insulin-stimulated phosphorylation of IRS-2 immobilized from either muscle or liver cells. IR1152 internalization in liver and muscle cells closely paralleled the ability of this mutant to phosphorylate IRS-2 in vivo in these cells. Block of receptor internalization (wild-type and mutant) in the liver and muscle cells also inhibited IRS-2, but not IRS-1, phosphorylation. Thus, the mechanisms controlling insulin receptor internalization differ in liver and skeletal muscle cells and may enable IR1152 to control glucose metabolism selectively in liver. In both cell types, receptor internalization seems necessary for IRS-2 but not IRS-1 phosphorylation.
Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
G. Vigliotta, C. Miele, S. Santopietro, G. Portella, A. Perfetti, M. A. Maitan, A. Cassese, F. Oriente, A. Trencia, F. Fiory, et al.
Overexpression of the ped/pea-15 Gene Causes Diabetes by Impairing Glucose-Stimulated Insulin Secretion in Addition to Insulin Action
Mol. Cell. Biol., June 1, 2004; 24(11): 5005 - 5015.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Hojlund, T. Hansen, M. Lajer, J. E. Henriksen, K. Levin, J. Lindholm, O. Pedersen, and H. Beck-Nielsen
A Novel Syndrome of Autosomal-Dominant Hyperinsulinemic Hypoglycemia Linked to a Mutation in the Human Insulin Receptor Gene
Diabetes, June 1, 2004; 53(6): 1592 - 1598.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Fiory, F. Oriente, C. Miele, C. Romano, A. Trencia, A. T. Alberobello, I. Esposito, R. Valentino, F. Beguinot, and P. Formisano
Protein Kinase C-{zeta} and Protein Kinase B Regulate Distinct Steps of Insulin Endocytosis and Intracellular Sorting
J. Biol. Chem., March 19, 2004; 279(12): 11137 - 11145.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
P. Vollenweider, B. Menard, and P. Nicod
Insulin Resistance, Defective Insulin Receptor Substrate 2--Associated Phosphatidylinositol-3' Kinase Activation, and Impaired Atypical Protein Kinase C ({zeta}/{lambda}) Activation in Myotubes From Obese Patients With Impaired Glucose Tolerance
Diabetes, April 1, 2002; 51(4): 1052 - 1059.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Oriente, P. Formisano, C. Miele, F. Fiory, M. A. Maitan, G. Vigliotta, A. Trencia, S. Santopietro, M. Caruso, E. Van Obberghen, et al.
Insulin Receptor Substrate-2 Phosphorylation Is Necessary for Protein Kinase Czeta Activation by Insulin in L6hIR Cells
J. Biol. Chem., September 28, 2001; 276(40): 37109 - 37119.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Caruso, M. A. Maitan, G. Bifulco, C. Miele, G. Vigliotta, F. Oriente, P. Formisano, and F. Beguinot
Activation and Mitochondrial Translocation of Protein Kinase Cdelta Are Necessary for Insulin Stimulation of Pyruvate Dehydrogenase Complex Activity in Muscle and Liver Cells
J. Biol. Chem., November 21, 2001; 276(48): 45088 - 45097.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2000 by the American Diabetes Association.