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

Fung, Michelle; Thompson, David; Shapiro, R. Jean; Warnock, Garth L.; Andersen, Dana K.; Elahi, Dariush; Meneilly, Graydon S.

doi:10.1016/j.diabres.2006.03.022

« Previous Next »Diabetes Research and Clinical Practice
Volume 74, Issue 2 , Pages 189-193, November 2006

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

Michelle Fung
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
David Thompson
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
R. Jean Shapiro
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
Garth L. Warnock
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
Dana K. Andersen
- Department of Surgery, University of Massachusetts Medical School, Worcester, MA, United States
Dariush Elahi
- Department of Surgery, University of Massachusetts Medical School, Worcester, MA, United States
Graydon S. Meneilly
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Corresponding author at: Division of Geriatric Medicine, Department of Medicine, Room 3300, 950 West 10th Ave, Vancouver, BC, Canada V5Z4E3. Tel.: +1 604 875 4045; fax: +1 604 875 4886.

Received 3 February 2006; accepted 20 March 2006. published online 18 April 2006.

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±29pM; type 2 diabetes: 68±20pM; transplant: 99±18pM, p=ns for all). GLP-1 had a significant incretin effect on transplanted islets but the response was less than controls (control: 2108±344pM; type 2 diabetes: 929±331pM; transplant: 329±112pM, 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.