Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells.

Abstract:

AIMS/HYPOTHESIS:A common G to A polymorphism ( UCSNP-43) in the Calpain 10 gene was recently found to be associated with Type II (non-insulin-dependent) diabetes mellitus and variations in post-absorptive and insulin stimulated glucose metabolism in vivo. We aimed to study the influence of Calpain 10 polymorphism on insulin action in fat cells. METHODS:Calpain 10 polymorphism ( UCSNP-19, -43 or -63) were set in relation to lipolysis and lipogenesis in isolated subcutaneous adipocytes of 46 apparently healthy non-obese subjects. RESULTS:For UCSNP-43 the G/G genotype had twofold higher basal and insulin stimulated rates as compared with AA/AG genotypes. However, there was no genotype effect on basal or insulin inhibited lipolysis rates in fat cells. The protein amount of GLUT 4 in adipocytes was not influenced by the polymorphism. Fat cells expressed mRNA for the Calpain 10 gene at a relatively high concentration, about 4 amol/microg RNA, which is similar to that of uncoupling protein-2. Neither a UCSNP-19 nor a UCSNP-63 polymorphism in the Calpain 10 gene was found to be associated with basal or insulin-induced adipocyte lipolysis and lipogenesis. None of the polymorphisms influenced body mass index or fasting plasma concentrations of insulin and glucose in 693 non-obese healthy subjects. CONCLUSIONS/INTERPRETATION:The Calpain 10 gene could be involved in the regulation of glucose metabolism but not lipolysis in human fat cells, although it does not involve adipocyte GLUT-4 protein content. It is possible that the Calpain 10 gene predisposes to diabetes by influencing the glucose metabolism.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Hoffstedt J,Rydén M,Löfgren P,Orho-Melander M,Groop L,Arner P

doi

10.1007/s00125-001-0732-2

subject

Has Abstract

pub_date

2002-02-01 00:00:00

pages

276-82

issue

2

eissn

0012-186X

issn

1432-0428

journal_volume

45

pub_type

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