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

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Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle. / Nilsson, Emma A; Poulsen, Pernille; Storgaard, Heidi; Almgren, Peter; Ling, Charlotte; Jensen, Christine Bjørn; Madsbad, Sten; Groop, Leif; Vaag, Allan; Ridderstråle, Martin.

In: Diabetes, Vol. 54, No. 10, 2005, p. 3015-3020.

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Nilsson, Emma A ; Poulsen, Pernille ; Storgaard, Heidi ; Almgren, Peter ; Ling, Charlotte ; Jensen, Christine Bjørn ; Madsbad, Sten ; Groop, Leif ; Vaag, Allan ; Ridderstråle, Martin. / Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle. In: Diabetes. 2005 ; Vol. 54, No. 10. pp. 3015-3020.

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TY - JOUR

T1 - Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle.

AU - Nilsson, Emma A

AU - Poulsen, Pernille

AU - Storgaard, Heidi

AU - Almgren, Peter

AU - Ling, Charlotte

AU - Jensen, Christine Bjørn

AU - Madsbad, Sten

AU - Groop, Leif

AU - Vaag, Allan

AU - Ridderstråle, Martin

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.2337/diabetes.54.10.3015

DO - 10.2337/diabetes.54.10.3015

M3 - Article

VL - 54

SP - 3015

EP - 3020

JO - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 10

ER -