Combination of Peptide YY(3–36) 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, 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 (S(I)) 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 S(I) were observed with any intervention. CONCLUSIONS: PYY(3–36) 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 PYY(3–36) 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 S(I).