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PMID: 3003151 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Diabetes-induced functional and structural changes in insulin receptors from rat skeletal muscle.

The Journal of clinical investigation ·Vol. 77 ·No. 1 ·1986-01-00 ·Pages 260-70

Burant CF, Treutelaar MK, Buse MG

Abstract

The effect of diabetes on the structure and function of insulin receptors was studied in rats 7 d after streptozotocin injection, using solubilized, partially purified receptors from rat hindlimb muscles. Diabetes increased the number of insulin receptors per gram of muscle 60-70% without apparent change in insulin binding affinity. Incubation of receptors at 4 degrees C with [gamma-32P]ATP and insulin resulted in dose-dependent autophosphorylation of the beta-subunit on tyrosine residues; receptors from diabetic rats showed decreased base-line phosphorylation, as well as a decrease in autophosphorylation at maximally stimulating insulin concentrations. These receptors also showed diminished exogenous substrate kinase activity using histone H2b and angiotensin II as phosphoacceptors. The electrophoretic mobility (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) of a subpopulation of beta-subunits derived from diabetics was slightly decreased; differences in electrophoretic mobility between control- and diabetic-derived beta-subunits were enhanced by generating fragments by partial Staphylococcus aureus V8 protease digestion. Endoglycosidase-H or neuraminidase treatment increased the electrophoretic mobility of beta-subunits in both groups, but only neuraminidase appeared to decrease or abolish differences in electrophoretic mobility between controls and diabetics, suggesting that excess sialilation may account, in part, for the altered mobility of diabetic derived beta-subunits. All structural and functional alterations in insulin receptors were prevented by treating diabetic rats with insulin for 60 h. Peripheral insulin resistance associated with insulinopenic diabetes may be related to modifications in insulin receptor structure, resulting in impaired signal transmission.

MeSH Terms
Acetylglucosaminidase/metabolism Animals Diabetes Mellitus, Experimental/metabolism,physiopathology Glycopeptides/metabolism Male Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Muscles/enzymology,metabolism Neuraminidase/metabolism Phosphopeptides/metabolism Phosphorylation Phosphotransferases/metabolism Rats Rats, Inbred Strains Receptor, Insulin/analysis,metabolism,physiology Substrate Specificity
Chemicals
Glycopeptides Phosphopeptides Phosphotransferases Receptor, Insulin Neuraminidase Acetylglucosaminidase Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Burant C F
Treutelaar M K
Buse M G
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43 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112285
Published
1986-01-00
Pages
260-70
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC423335
Subset
IM
Grants
NIADDK NIH HHS · AM-02001 · United States
External Links
PubMed source DOI: 10.1172/JCI112285 PMC Full Text View journal details
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