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

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, PYY3-36 and GLP-1(7-36) amide, on glucose homeostasis are unknown. Objective: This study sought to investigate the acute effects of PYY3-36 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 PYY3-36 alone, GLP-1(7-36) amide alone, and a combination of PYY3-36 and GLP-1(7-36) (amide) on acute insulin response to glucose (AIRg) and insulin sensitivity index (S-I) in 14 overweight human volunteers, studied in a clinical research facility. Results: PYY3-36 alone caused a small but nonsignificant increase in AIRg. GLP-1(7-36) amide alone and the combination of PYY3-36 and GLP-1(7-36) (amide) did increase AIRg significantly. No significant differences in S-I were observed with any intervention. Conclusions: PYY3-36 lacks any significant acute effects on first-phase insulin secretion or S-I 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 PYY3-36 and GLP-1(7-36) amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on S-I.