Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells.
OBJECTIVE
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
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.
Hoffstedt
J
J
Department of Medicine, Huddinge University Hospital (CME), Stockholm, Sweden.
Rydén
M
M
Löfgren
P
P
Orho-Melander
M
M
Groop
L
L
Arner
P
P
D000225:Adenine; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D002154:Calpain / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006147:Guanine; D006801:Humans; D008066:Lipolysis / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic
D017931:DNA Primers; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D006147:Guanine; D002154:Calpain; C415197:calpain 10; D005947:Glucose; D000225:Adenine