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

• Published in: The journal of clinical endocrinology and metabolism 2014-11, Vol.99 (11), p.E2317-E2324
• Main Authors: Tan, Tricia M, Salem, Victoria, Troke, Rachel C, Alsafi, Ali, Field, Benjamin C T, De Silva, Akila, Misra, Shivani, Baynes, Kevin C R, Donaldson, Mandy, Minnion, James, Ghatei, Mohammad A, Godsland, Ian F, Bloom, Stephen R
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1945-7197
• DOI: 10.1210/jc.2014-2143

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. 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. 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. 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. 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.