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

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.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 10/2008; 94(1):181-9. DOI: 10.1210/jc.2008-1806
Source: PubMed


Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced beta-cell secretory capacity indicates a low functional beta-cell mass.
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.
The study was performed in a clinical and translational research center.
Five intraportal islet and six portally drained pancreas transplant recipients participated in the study.
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.
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).
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.

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    • "The biggest obstacle in islet transplantation is limited supply of donor islets, thus great efforts have been directed at strategies of " pure " β-cell replacement derived from stem cells (Ramiya et al., 2000) or surrogates (Newgard, 1994)—the panacea of the " cure " for diabetes! Of note, not only β-cell but also α-cell mass in transplanted islets are reduced, with surviving α-cells suffering from defective response to glucose and incretin hormone glucagon-like peptide-1 (GLP-1) (Newgard, 1994; Gupta et al., 1997; Paty et al., 2002; Zhou et al., 2008; Rickels et al., 2009). "
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