Source
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 700 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6149, USA. rickels@mail.med.upenn.edu
Abstract
CONTEXT:
Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced beta-cell secretory capacity indicates a low functional beta-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 beta-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 beta-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 beta-cell mass that may be associated with depletion of mature beta-cell secretory granules.