Effect of glucagon-like peptide-1 (7–37) on beta-cell function after islet transplantation in type 1 diabetes

Abstract

Islet transplantation can improve glycemic control in patients with type 1 diabetes and reduce or eliminate the need for insulin. Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose induced insulin secretion, and has a trophic effect on beta-cells. We evaluated the effect of GLP-1 on insulin secretion after islet transplantation. Patients underwent hyperglycemic glucose clamp studies 1 month after their last transplant. GLP-1 was infused during the second hour of the hyperglycemic clamp. Results were compared to normal control subjects and patients with type 2 diabetes who underwent an identical hyperglycemic clamp. First phase insulin release was absent in patients, while second phase insulin was not significantly reduced (control: 118 ± 29 pM; type 2 diabetes: 68 ± 20 pM; transplant: 99 ± 18 pM, p = ns for all). GLP-1 had a significant incretin effect on transplanted islets but the response was less than controls (control: 2108 ± 344 pM; type 2 diabetes: 929 ± 331 pM; transplant: 329 ± 112 pM, p < 0.0001 control versus transplant). Islet transplant patients had no evidence of resistance to insulin mediated glucose disposal. We conclude that transplanted islets retain the ability to respond to GLP-1.