title: Genetic and nongenetic regulation of CAPN10 mRNA expression in skeletal muscle.
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.
authors.affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden. emma.carlsson@endo.mas.lu.se
authors.forename: Emma
authors.initials: E
authors.lastname: Carlsson
authors.forename: Pernille
authors.initials: P
authors.lastname: Poulsen
authors.forename: Heidi
authors.initials: H
authors.lastname: Storgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Christine Bjørn
authors.initials: CB
authors.lastname: Jensen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Martin
authors.initials: M
authors.lastname: Ridderstråle
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D002154:Calpain / Q000235:genetics*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis*; D018433:Twin Studies as Topic; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012333:RNA, Messenger; D002154:Calpain; C415197:calpain 10