β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes

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Roux-en-Y gastric bypass (RYGB) improves glucose tolerance in patients with type 2 diabetes, but the effect on β-cell sensitivity to glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) remains unclear. We performed oral glucose tolerance tests (OGTTs) and hyperglycemic clamps (at 15 mmol/L) with GIP, GLP-1, or saline coinfusions before and 1 week and 3 months after RYGB in nine patients with preoperative type 2 diabetes. During OGTTs, fasting plasma glucose normalized, while glucose tolerance, GLP-1, and insulin secretion increased markedly after RYGB. During clamped hyperglycemia with saline coinfusion, first- and second-phase insulin secretion increased after RYGB. GLP-1 and GIP coinfusions clearly potentiated insulin secretion before and after surgery, but the potentiation of insulin secretion, expressed relative to insulin secretion during saline coinfusion, was reduced after surgery during GLP-1 (first- and second-phase insulin secretion) and GIP (only first-phase insulin secretion) coinfusion. Thus, insulin secretion increased in response to oral and i.v. glucose, but the sensitivity of the β-cell to GLP-1 seemed reduced after RYGB. Accordingly, the improved β-cell function after RYGB in patients with preoperative type 2 diabetes is driven by enhanced GLP-1 secretion upon oral stimulation and improved β-cell response to glucose, but not an improved sensitivity of the β-cells to incretins. ARTICLE HIGHLIGHTS Roux-en-Y gastric bypass improves glycemic control in patients with type 2 diabetes, but the impact of the improved glycemic control on β-cell sensitivity to glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is sparsely described. GLP-1 and GIP potentiated insulin secretion during clamped hyperglycemia before and after surgery, but, when related to the response to glucose alone, the relative potentiating effects of GIP (on first-phase insulin secretion) and GLP-1 (on first- and second-phase insulin secretion) were reduced postoperatively. The improvement in β-cell function after Roux-en-Y gastric bypass in patients with type 2 diabetes is not driven by improved β-cell sensitivity to incretins but rather other factors, including improved β-cell sensitivity to the changed glucose response and exaggerated postprandial GLP-1.

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