Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Poster Board MON-673
Methods: Twenty three subjects were studied: 6 lean (body mass index BMI 20-25 kg/m2) 6 obese (BMI>30 kg/m2) with normal glucose tolerance; 6 obese with impaired glucose tolerance (IGT) and 5 obese with type 2 diabetes (T2DM) on diet only. The protocol included two visits for each participant: during a hyperglycaemic clamp (8mmol/L) for 240 minutes either GIP (2 pmol/kg/min) or placebo were infused in a randomized order. Blood samples were taken in the fasting state and at six further timepoints during the 240 min infusion for measurement of glucose, insulin, TAGs and FFAs. Abdominal SAT biopsies were obtained in the basal state and at the end of GIP/placebo infusion. Gene expression of SAT enzymes was quantified by RNA extraction and quantitative PCR methods.
Results: GIP increased insulin secretion in all groups except in the T2DM group. Circulating FFAs were significantly reduced after GIP infusion compared to placebo in T2DM group (-382 vs -219 umol/l; p=0.05). Similar trends in FFAs were observed in the IGT group (-393 umol/l after GIP vs -336 umol/l after placebo) but did not reach statistical significance. Circulating TAGs showed slight reduction in all groups with no difference between GIP or placebo. LPL expression increased in T2DM and IGT patients after GIP infusion by 31% and 13% from baseline respectively, although did not reach statistical significance. ATGL expression was higher after GIP or placebo infusion for all the groups. The increase in ATGL expression was higher after GIP infusion (38% vs 11%) compared with placebo in the T2DM group although did not reach statistical significance. No change in HSL expression was observed after GIP infusion compared with placebo.
Conclusion: We have shown that in obese patients with T2DM, acute GIP infusion under hyperglycaemic clamp conditions reduced circulating FFAs implying an increased FFA incorporation within SAT. This occurred despite the lack of enhanced insulin secretion by GIP in the T2DM group suggesting an independent role of GIP. We have also shown that GIP may enhance LPL expression within SAT in obese patients with T2DM and IGT and increases ATGL expression in T2DM. It remains to be shown if the effects of GIP on LPL and ATGL expression result in an altered rate of lipolysis in IGT and T2DM.
Disclosure: DC: Principal Investigator, Ipsen, Principal Investigator, Pfizer, Inc., Principal Investigator, Otsuka, Principal Investigator, Novo Nordisk, Principal Investigator, Ipsen, Principal Investigator, Otsuka. JW: Principal Investigator, Abbott Laboratories, Principal Investigator, Astra Zeneca, Principal Investigator, Bristol-Myers Squibb, Principal Investigator, GlaxoSmithKline, Principal Investigator, Eli Lilly & Company, Principal Investigator, Merck & Co., Principal Investigator, Novo Nordisk, Principal Investigator, Johnson &Johnson. CD: Principal Investigator, Eli Lilly & Company, Principal Investigator, Novo Nordisk, Principal Investigator, Merck & Co., Principal Investigator, Otsuka. Nothing to Disclose: SKT, CY, SM, CW
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