Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans.
Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increases blood flow and triglyceride (TAG) clearance in subcutaneous (sc) abdominal adipose tissue in lean humans. The present experiments were performed to further investigate the role of insulin for the vasoactive effect of GIP in adipose tissue metabolism and whether the vasodilatory effect of GIP is dependent on C-peptide.



Six lean healthy subjects were studied. The sc abdominal adipose tissue metabolism was assessed by Fick's principle during GIP infusion (1.5 pmol/kg/min) in combination with 1) euglycemic-high insulinemic clamp (Eugluc-Hiinsu), raising plasma insulin concentrations to postprandial levels, 2) hyperglycemic-euinsulinemic clamp (Hygluc-Euinsu), and 3) hyperglycemic-hyperinsulinemic clamp, raising plasma insulin concentrations to supraphysiological levels. During the hyperglycemic clamps, endogenous insulin and C-peptide secretion were inhibited by infusion of the somatostatin analogue octreotide.



During GIP infusion, Eugluc-Hiinsu, and hyperglycemic-hyperinsulinemic clamps, sc abdominal adipose tissue blood flow (ATBF) was similar and increased from 2.1 ± 0.2 and 2.2 ± 0.4 ml min(-1) (100 g tissue)(-1) to 7.1 ± 0.6 and 7.6 ± 0.1 ml min(-1) (100 g tissue)(-1), respectively (P < .01). ATBF remained virtually constant (2.7 ± 0.4 ml min(-1) [100 g tissue](-1)) during Hygluc-Euinsu and GIP infusion. In addition, adipose tissue TAG clearance increased significantly (P = .03), whereas free fatty acid output (P = .01), glycerol output (P = .02) and free fatty acid/glycerol release ratio (P = .04) decreased during the Eugluc-Hiinsu clamp compared to Hygluc-Euinsu clamp with GIP.



In healthy lean humans, insulin is permissive for GIP to induce an increase in blood flow and TAG clearance in sc abdominal adipose tissue. This effect is independent of C-peptide.
Department of Clinical Physiology/Nuclear Medicine (M.A., L.S., A.A., J.B.), Bispebjerg University Hospital, Copenhagen, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences (J.J.H., J.B.), University of Copenhagen, Copenhagen, Denmark; Xlab, Center for Healthy Ageing (F.D.), University of Copenhagen, Denmark; Department of Geriatrics (F.D.), Bispebjerg University Hospital, Copenhagen, Denmark.
Meena
M
Asmar
Department of Clinical Physiology/Nuclear Medicine (M.A., L.S., A.A., J.B.), Bispebjerg University Hospital, Copenhagen, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences (J.J.H., J.B.), University of Copenhagen, Copenhagen, Denmark; Xlab, Center for Healthy Ageing (F.D.), University of Copenhagen, Denmark; Department of Geriatrics (F.D.), Bispebjerg University Hospital, Copenhagen, Denmark.
Lene
L
Simonsen
Department of Clinical Physiology/Nuclear Medicine (M.A., L.S., A.A., J.B.), Bispebjerg University Hospital, Copenhagen, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences (J.J.H., J.B.), University of Copenhagen, Copenhagen, Denmark; Xlab, Center for Healthy Ageing (F.D.), University of Copenhagen, Denmark; Department of Geriatrics (F.D.), Bispebjerg University Hospital, Copenhagen, Denmark.
Ali
A
Asmar
Department of Clinical Physiology/Nuclear Medicine (M.A., L.S., A.A., J.B.), Bispebjerg University Hospital, Copenhagen, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences (J.J.H., J.B.), University of Copenhagen, Copenhagen, Denmark; Xlab, Center for Healthy Ageing (F.D.), University of Copenhagen, Denmark; Department of Geriatrics (F.D.), Bispebjerg University Hospital, Copenhagen, Denmark.
Jens Juul
JJ
Holst
Department of Clinical Physiology/Nuclear Medicine (M.A., L.S., A.A., J.B.), Bispebjerg University Hospital, Copenhagen, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences (J.J.H., J.B.), University of Copenhagen, Copenhagen, Denmark; Xlab, Center for Healthy Ageing (F.D.), University of Copenhagen, Denmark; Department of Geriatrics (F.D.), Bispebjerg University Hospital, Copenhagen, Denmark.
Flemming
F
Dela
Department of Clinical Physiology/Nuclear Medicine (M.A., L.S., A.A., J.B.), Bispebjerg University Hospital, Copenhagen, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences (J.J.H., J.B.), University of Copenhagen, Copenhagen, Denmark; Xlab, Center for Healthy Ageing (F.D.), University of Copenhagen, Denmark; Department of Geriatrics (F.D.), Bispebjerg University Hospital, Copenhagen, Denmark.
Jens
J
Bülow
D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D018592:Cross-Over Studies; D004357:Drug Synergism; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D050507:Subcutaneous Fat, Abdominal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D055815:Young Adult
D007328:Insulin; D014662:Vasoconstrictor Agents; D005749:Gastric Inhibitory Polypeptide