Acute Effects of Co-infusion of Peptide YY(3-36) and Glucagon-like Peptide-1 on Insulin Secretion and Insulin Sensitivity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-670
Tricia Tan1, Victoria Salem2, Rachel Troke*3, Akila De Silva3, Ali Alsafi2, Shivani Misra2, Kevin Baynes2, Mohammad A Ghatei4, James S Minnion3, Benjamin Field2, Ian F Godsland4 and Stephen R Bloom3
1Imperial College London, 2Imperial College London, United Kingdom, 3Imperial College London, London, United Kingdom, 4Imperial College of Medicine, London, United Kingdom
The amelioration of Type 2 Diabetes and sustained weight loss after bariatric surgery are thought to be due to elevated circulating levels of the gut hormones Peptide YY 3-36 (PYY3-36) and Glucagon-Like Peptide-1 (GLP-1). GLP-1 augments the insulin response to an oral glucose load. PYY3-36 has appetite-inhibitory effects and contributes to longer-term weight loss. Rodent studies provide conflicting data regarding the effects of PYY on glucose homeostasis: PYY may enhance insulin-mediated glucose disposal, but in vitro evidence suggests that the activation of Y1-receptors (which mediate the effects of PYY on pancreatic islet cells) may inhibit insulin release. No study to date has examined the effects of PYY, either alone or in combination with GLP-1, in humans.

Hypothesis

GLP-1 will exert a beneficial effect on glucose homeostasis in healthy, overweight human volunteers, and co-administration with PYY3-36 will not attenuate this response.

Methods

14 overweight healthy volunteers were studied in a single-blinded crossover fashion. They were randomised to receive four infusions: 1) vehicle; 2) GLP-1 at 0.2 pmol/kg/min; 3) PYY3-36 at 0.15 pmol/kg/min; and 4) co-infusion of GLP-1 plus PYY3-36 at the above doses. During each intervention, a Frequently Sampled Intravenous Glucose Tolerance Test was performed to assess acute insulin response to glucose (AIRg), and insulin sensitivity (Si), using Minimal Modeling.

Results

AIRg was significantly increased by infusion of GLP-1 alone, compared to all other interventions (p<0.05). No acute effect on Si was noted with any of the interventions.  The disposition index (AIRg ´ Si) was significantly greater following administration of GLP-1 alone than with any other intervention (p<0.05).

Conclusion

GLP-1 infusion increases the AIRg in healthy, overweight humans.  In contrast, PYY infusion had no effect on AIRg and neither hormone, alone or in combination, was shown to enhance Si in the acute setting.

Nothing to Disclose: TT, VS, RT, AD, AA, SM, KB, MAG, JSM, BF, IFG, SRB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm