Document Detail


Muscle fiber type-specific defects in insulin signal transduction to glucose transport in diabetic GK rats.
MedLine Citation:
PMID:  10078575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To determine whether defects in the insulin signal transduction pathway to glucose transport occur in a muscle fiber type-specific manner, post-receptor insulin-signaling events were assessed in oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skeletal muscle from Wistar or diabetic GK rats. In soleus muscle from GK rats, maximal insulin-stimulated (120 nmol/l) glucose transport was significantly decreased, compared with that of Wistar rats. In EDL muscle from GK rats, maximal insulin-stimulated glucose transport was normal, while the submaximal response was reduced compared with that of Wistar rats. We next treated diabetic GK rats with phlorizin for 4 weeks to determine whether restoration of glycemia would lead to improved insulin signal transduction. Phlorizin treatment of GK rats resulted in full restoration of insulin-stimulated glucose transport in soleus and EDL muscle. In soleus muscle from GK rats, submaximal and maximal insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and IRS-1-associated phosphatidylinositol (PI) 3-kinase activity were markedly reduced, compared with that of Wistar rats, but only submaximal insulin-stimulated PI 3-kinase was restored after phlorizin treatment. In EDL muscle, insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1-associated PI-3 kinase were not altered between GK and Wistar rats. Maximal insulin-stimulated Akt (protein kinase B) kinase activity is decreased in soleus muscle from GK rats and restored upon normalization of glycemia (Krook et al., Diabetes 46:2100-2114, 1997). Here, we show that in EDL muscle from GK rats, maximal insulin-stimulated Akt kinase activity is also impaired and restored to Wistar rat levels after phlorizin treatment. In conclusion, functional defects in IRS-1 and PI 3-kinase in skeletal muscle from diabetic GK rats are fiber-type-specific, with alterations observed in oxidative, but not glycolytic, muscle. Furthermore, regardless of muscle fiber type, downstream steps to PI 3-kinase (i.e., Akt and glucose transport) are sensitive to changes in the level of glycemia.
Authors:
X M Song; Y Kawano; A Krook; J W Ryder; S Efendic; R A Roth; H Wallberg-Henriksson; J R Zierath
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  48     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-03-30     Completed Date:  1999-03-30     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  664-70     Citation Subset:  AIM; IM    
Affiliation:
Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
3-O-Methylglucose / pharmacokinetics
Animals
Biological Transport / drug effects
Body Weight
Diabetes Mellitus, Type 2 / genetics,  physiopathology*
Gene Expression Regulation* / drug effects
Glucose / metabolism*
Glucose Transporter Type 4
Glycogen Synthase / genetics
Insulin / physiology*
Insulin Receptor Substrate Proteins
Monosaccharide Transport Proteins / genetics
Muscle Fibers, Skeletal / drug effects,  metabolism*
Muscle Proteins*
Muscle, Skeletal / drug effects,  metabolism*
Phlorhizin / pharmacology
Phosphatidylinositol 3-Kinases / genetics,  metabolism
Phosphoproteins / genetics,  metabolism
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Rats
Rats, Inbred Strains
Rats, Wistar
Signal Transduction / physiology*
Species Specificity
Grant Support
ID/Acronym/Agency:
DK-34926/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Glucose Transporter Type 4; 0/Insulin; 0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, rat; 0/Monosaccharide Transport Proteins; 0/Muscle Proteins; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 0/Slc2a4 protein, rat; 146-72-5/3-O-Methylglucose; 50-99-7/Glucose; 60-81-1/Phlorhizin; EC 2.4.1.11/Glycogen Synthase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Akt1 protein, rat; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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