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Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle.

Nilsson, Emma A LU ; Poulsen, Pernille; Storgaard, Heidi; Almgren, Peter LU ; Ling, Charlotte LU ; Jensen, Christine Bjørn; Madsbad, Sten; Groop, Leif LU ; Vaag, Allan and Ridderstråle, Martin LU (2005) In Diabetes 54(10). p.3015-3020
Abstract
The gene encoding calpain-10 (CAPN10) has been identified as a candidate gene for type 2 diabetes. Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs. Muscle biopsies were obtained before and after hyperinsulinemic-euglycemic clamps from 166 young and elderly monozygotic and dizygotic twins as well as from 15 subjects with normal (NGT) or impaired glucose tolerance (IGT) exposed to an Intralipid infusion. We found hereditary effects on both basal and insulin-exposed CAPN10 mRNA expression. Carriers of the type 2 diabetes–associated single nucleotide polymorphism (SNP)-43 G/G... (More)
The gene encoding calpain-10 (CAPN10) has been identified as a candidate gene for type 2 diabetes. Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs. Muscle biopsies were obtained before and after hyperinsulinemic-euglycemic clamps from 166 young and elderly monozygotic and dizygotic twins as well as from 15 subjects with normal (NGT) or impaired glucose tolerance (IGT) exposed to an Intralipid infusion. We found hereditary effects on both basal and insulin-exposed CAPN10 mRNA expression. Carriers of the type 2 diabetes–associated single nucleotide polymorphism (SNP)-43 G/G genotype had reduced CAPN10 mRNA levels compared with subjects carrying the SNP-43 A-allele. Age had no significant influence on CAPN10 mRNA levels. Insulin had no significant effect on CAPN10 mRNA levels, neither in the twins nor in the basal state of the Intralipid study. However, after a 24-h infusion of Intralipid, we noted a significant increase in CAPN10 mRNA in response to insulin in subjects with NGT but not in subjects with IGT. In conclusion, we provide evidence that mRNA expression of CAPN10 in skeletal muscle is under genetic control. Glucose-tolerant but not glucose-intolerant individuals upregulate their CAPN10 mRNA levels in response to prolonged exposure to fat. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
54
issue
10
pages
3015 - 3020
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000232237400026
  • pmid:16186407
  • scopus:25844477623
ISSN
1939-327X
DOI
10.2337/diabetes.54.10.3015
language
English
LU publication?
yes
id
ce843b02-d21e-4168-848a-da778767f4f2 (old id 143376)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16186407&dopt=Abstract
date added to LUP
2007-07-17 09:52:35
date last changed
2017-01-01 07:16:38
@article{ce843b02-d21e-4168-848a-da778767f4f2,
  abstract     = {The gene encoding calpain-10 (CAPN10) has been identified as a candidate gene for type 2 diabetes. Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs. Muscle biopsies were obtained before and after hyperinsulinemic-euglycemic clamps from 166 young and elderly monozygotic and dizygotic twins as well as from 15 subjects with normal (NGT) or impaired glucose tolerance (IGT) exposed to an Intralipid infusion. We found hereditary effects on both basal and insulin-exposed CAPN10 mRNA expression. Carriers of the type 2 diabetes–associated single nucleotide polymorphism (SNP)-43 G/G genotype had reduced CAPN10 mRNA levels compared with subjects carrying the SNP-43 A-allele. Age had no significant influence on CAPN10 mRNA levels. Insulin had no significant effect on CAPN10 mRNA levels, neither in the twins nor in the basal state of the Intralipid study. However, after a 24-h infusion of Intralipid, we noted a significant increase in CAPN10 mRNA in response to insulin in subjects with NGT but not in subjects with IGT. In conclusion, we provide evidence that mRNA expression of CAPN10 in skeletal muscle is under genetic control. Glucose-tolerant but not glucose-intolerant individuals upregulate their CAPN10 mRNA levels in response to prolonged exposure to fat.},
  author       = {Nilsson, Emma A and Poulsen, Pernille and Storgaard, Heidi and Almgren, Peter and Ling, Charlotte and Jensen, Christine Bjørn and Madsbad, Sten and Groop, Leif and Vaag, Allan and Ridderstråle, Martin},
  issn         = {1939-327X},
  language     = {eng},
  number       = {10},
  pages        = {3015--3020},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle.},
  url          = {http://dx.doi.org/10.2337/diabetes.54.10.3015},
  volume       = {54},
  year         = {2005},
}