PMID- 27258938 OWN - NLM STAT- MEDLINE DCOM- 20170626 LR - 20180501 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 101 IP - 8 DP - 2016 Aug TI - Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans. PG - 3155-62 LID - 10.1210/jc.2016-1933 [doi] AB - CONTEXT AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. FAU - Asmar, Meena AU - Asmar M AD - 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. FAU - Simonsen, Lene AU - Simonsen L AD - 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. FAU - Asmar, Ali AU - Asmar A AD - 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. FAU - Holst, Jens Juul AU - Holst JJ AD - 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. FAU - Dela, Flemming AU - Dela F AD - 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. FAU - Bulow, Jens AU - Bulow J AD - 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. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20160603 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Insulin) RN - 0 (Vasoconstrictor Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Adipose Tissue/blood supply/*drug effects/*metabolism MH - Adult MH - Cross-Over Studies MH - Drug Synergism MH - Gastric Inhibitory Polypeptide/*pharmacology MH - Glucose Clamp Technique MH - Humans MH - Insulin/*pharmacology MH - Male MH - Regional Blood Flow/drug effects MH - Subcutaneous Fat, Abdominal/blood supply/drug effects/metabolism MH - Vasoconstriction/*drug effects MH - Vasoconstrictor Agents/pharmacology MH - Young Adult EDAT- 2016/06/04 06:00 MHDA- 2017/06/27 06:00 CRDT- 2016/06/04 06:00 PHST- 2016/06/04 06:00 [entrez] PHST- 2016/06/04 06:00 [pubmed] PHST- 2017/06/27 06:00 [medline] AID - 10.1210/jc.2016-1933 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2016 Aug;101(8):3155-62. doi: 10.1210/jc.2016-1933. Epub 2016 Jun 3.