Gastric bypass alters both glucose-dependent and glucose-independent regulation of islet hormone secretion

Objective Roux-en-Y gastric bypass surgery (GB) is characterized by accentuated but short-lived postprandial elevations of blood glucose and insulin. This profile has been attributed to effects of relative hyperglycemia to directly stimulate β-cells and an augmented incretin effect. An additional glucose-independent stimulation of insulin secretion in GB subjects was hypothesized. Methods Fifteen subjects with prior GB, six matched obese non surgical controls, and seven lean individuals were recruited. Islet hormones were measured before and after meal ingestion during hyperinsulinemic hypoglycemic clamps to minimize the direct effects of glycemia and glucose-dependent gastrointestinal hormones on insulin secretion. Results The GB subjects had less suppression of fasting β-cell secretion during the insulin clamp compared to controls. In addition, meal-induced insulin secretion increased in the GB subjects but not controls during fixed sub-basal glycemia. In contrast, the glucagon responses to hypoglycemia and meal ingestion were lower in the GB subjects than controls. Conclusions Among subjects with GB, the response of insulin and glucagon secretion to decreasing blood glucose is blunted, but meal-induced insulin secretion is stimulated even at fixed systemic sub-basal glycemia. These findings indicate that, following GB, islet hormone secretion is altered as a result of factors beyond circulatory glucose levels.