Fasting-Induced Changes in Glucagon Secretion Are Dysregulated in Obesity

Hyperglucagonemia is a hallmark in obesity and type 2 diabetes (T2DM). Suppression of glucagon signaling improves glycemic control in T2DM. We evaluated glucagon homeostasis in lean and obese mice and people. Discordant with the canonical rise in glucagon with fasting, our studies show that fasting (4, 8, 16 and 24 h) caused a progressive decrease in serum glucagon in diet-induced obese, hyperglucagonemic mice (P Disclosure J.H. Stern: None. G.I. Smith: None. R.H. Unger: None. S. Klein: Stock/Shareholder; Self; Aspire Bariatrics. Consultant; Self; Pfizer Inc.. Research Support; Self; Merck & Co., Inc., Johnson & Johnson Services, Inc., REMD Biotherapeutics. P.E. Scherer: None.