title: Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus.
abstract: Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M-values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin-mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS.
authors.affiliation: Department of Surgery and Peri-Operative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden. toralph.ruge@vll.se
authors.forename: Toralph
authors.initials: T
authors.lastname: Ruge
authors.forename: Valentina
authors.initials: V
authors.lastname: Sukonina
authors.forename: Olessia
authors.initials: O
authors.lastname: Kroupa
authors.forename: Elena
authors.initials: E
authors.lastname: Makoveichuk
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lundgren
authors.forename: Maria K
authors.initials: MK
authors.lastname: Svensson
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: Jan W
authors.initials: JW
authors.lastname: Eriksson
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002352:Carrier Proteins / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008071:Lipoprotein Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D018110:Receptors, Lipoprotein
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D001786:Blood Glucose; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; C523701:GPIHBP1 protein, human; D007328:Insulin; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase