A Calpain-10 Gene Polymorphism is Associated with Reduced Muscle MRNA Levels and Insulin Resistance

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2000 Oct 6

PMID 11018080

Citations 72

Authors

L J Baier

P A Permana

X Yang

R E Pratley

R L Hanson

G Q Shen

D Mott

W C Knowler

N J Cox

Y Horikawa

N Oda

G I Bell

C Bogardus

Affiliations

Soon will be listed here.

Abstract

Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G-->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 G/G genotype was not associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced CAPN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.

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