Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Clin Endocrinol Metab. 2009 Jan;94(1):181-9. doi: 10.1210/jc.2008-1806. Epub 2008 Oct 28.

Effect of glucagon-like peptide-1 on beta- and alpha-cell function in isolated islet and whole pancreas transplant recipients.

Author information

  • 1Department 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.

PMID:
18957498
[PubMed - indexed for MEDLINE]
PMCID:
PMC2630873
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Write to the Help Desk