title: Gene expression of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects.
abstract: The gene of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase gives rise to several splice variants. We hypothesized that the expression of p85alpha splice variants may be altered in skeletal muscle from subjects with type 2 diabetes mellitus. Skeletal muscle biopsies were obtained from nine type 2 diabetic and eight healthy men, matched for age, body mass index (BMI) and physical fitness. PI 3-kinase activity in skeletal muscle following in vitro insulin stimulation was reduced in subjects with type 2 diabetes. p85alpha mRNA was elevated fourfold in type 2 diabetic as compared to healthy control subjects ( P<0.05). p85alpha mRNA abundance was positively correlated with plasma insulin concentration ( P<0.01) and serum glucose concentration ( P<0.01). Despite this, protein levels of p85alpha, p55alpha, and the novel human p50alpha were not altered in type 2 diabetic subjects. Thus, although gene expression of full-length p85alpha is increased in skeletal muscle from type 2 diabetics, this is not reflected by increased protein levels. Therefore, defects in PI 3-kinase activity are likely due to impaired activation of the enzyme rather than changes in protein expression of the isoforms of the regulatory subunit.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tsuchida
authors.forename: Marie
authors.initials: M
authors.lastname: Björnholm
authors.forename: Maria
authors.initials: M
authors.lastname: Fernström
authors.forename: Dana
authors.initials: D
authors.lastname: Galuska
authors.forename: Per
authors.initials: P
authors.lastname: Johansson
authors.forename: Harriet
authors.initials: H
authors.lastname: Wallberg-Henriksson
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Staffan
authors.initials: S
authors.lastname: Lake
authors.forename: Anna
authors.initials: A
authors.lastname: Krook
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases