Effect of Glucagon-Like Peptide-1 on β- and α-Cell Function in Isolated Islet and Whole Pancreas Transplant Recipients

Context: Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced β-cell secretory capacity indicates a low functional β-cell mass. Objective: We sought to determine whether glucagon-like peptide-1 (GLP-1) enhanced glucose-dependent insulin secretion and glucagon suppression in islet recipients, and whether GLP-1 effects were dependent on functional β-cell mass by simultaneously studying recipients of whole pancreas transplants. Setting: The study was performed in a clinical and translational research center. Participants: Five intraportal islet and six portally drained pancreas transplant recipients participated in the study. Intervention: Subjects underwent glucose-potentiated arginine testing with GLP-1 (1.5 pmol · kg−1 · min−1) or placebo infused on alternate randomized occasions, with 5 g arginine injected under basal and hyperglycemic clamp conditions. Results: Basal glucose was lower with increases in insulin and decreases in glucagon during GLP-1 vs. placebo in both groups. During the hyperglycemic clamp, a significantly greater glucose infusion rate was required with GLP-1 vs. placebo in both groups (P < 0.05), an effect more pronounced in the pancreas vs. islet group (P < 0.01). The increased glucose infusion rate was associated with significant increases in second-phase insulin secretion in both groups (P < 0.05) that also tended to be greater in the pancreas vs. islet group (P = 0.08), whereas glucagon was equivalently suppressed by the hyperglycemic clamp during GLP-1 and placebo infusions in both groups. The GLP-1-induced increase in second-phase insulin correlated with the β-cell secretory capacity (P < 0.001). The proinsulin secretory ratio (PISR) during glucose-potentiated arginine was significantly greater with GLP-1 vs. placebo infusion in both groups (P < 0.05). Conclusions: GLP-1 induced enhancement of glucose-dependent insulin secretion, but not glucagon suppression, in islet and pancreas transplant recipients, an effect dependent on the functional β-cell mass that may be associated with depletion of mature β-cell secretory granules.