Combination of peptide YY3-36 with GLP-1(7-36) amide causes an increase in first-phase insulin secretion after IV glucose

J Clin Endocrinol Metab. 2014 Nov;99(11):E2317-24. doi: 10.1210/jc.2014-2143. Epub 2014 Aug 21.

Abstract

Context: The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY(3-36) and GLP-1(7-36 amide), on glucose homeostasis are unknown.

Objective: This study sought to investigate the acute effects of PYY(3-36) and GLP-1(7-36) amide, individually and in combination, on insulin secretion and sensitivity.

Setting and design: Using a frequently sampled iv glucose tolerance test (FSIVGTT) and minimal modeling, this study measured the effects of PYY(3-36) alone, GLP-1(7-36) amide alone, and a combination of PYY(3-36) and GLP-1(7-36) amide on acute insulin response to glucose (AIRg) and insulin sensitivity index (SI) in 14 overweight human volunteers, studied in a clinical research facility.

Results: PYY(3-36) alone caused a small but nonsignificant increase in AIRg. GLP-1(7-36) amide alone and the combination of PYY(3-36) and GLP-1(7-36) amide did increase AIRg significantly. No significant differences in SI were observed with any intervention.

Conclusions: PYY(3-36) lacks any significant acute effects on first-phase insulin secretion or SI when tested using an FSIVGTT. Both GLP-1(7-36) amide alone and the combination of PYY3-36 and GLP-1(7-36) amide increase first-phase insulin secretion. There does not seem to be any additive or synergistic effect between PYY(3-36) and GLP-1(7-36) amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on SI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Female
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucose / administration & dosage*
  • Glucose Tolerance Test
  • Homeostasis / drug effects
  • Humans
  • Insulin / blood*
  • Insulin Resistance
  • Male
  • Middle Aged
  • Obesity / blood*
  • Overweight / blood*
  • Peptide Fragments / pharmacology*
  • Peptide YY / pharmacology*
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • Peptide YY
  • glucagon-like peptide 1 (7-36)amide
  • peptide YY (3-36)
  • Glucagon-Like Peptide 1
  • Glucose