Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2010 Mar;95(3):1238-46. doi: 10.1210/jc.2009-2289. Epub 2010 Jan 22.

{beta}-Cell secretory capacity and demand in recipients of islet, pancreas, and kidney transplants.

Author information

1
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:

beta-Cell secretory capacity, a measure of functional beta-cell mass, is often impaired in islet transplant recipients, likely because of a low engrafted beta-cell mass, although calcineurin inhibitor toxicity is often cited as the explanation.

OBJECTIVE:

We sought to determine whether use of the calcineurin inhibitor tacrolimus was associated with reduced beta-cell secretory capacity or with increased beta-cell secretory demand independent of engrafted islet mass.

DESIGN AND PARTICIPANTS:

We compared metabolic measures in five intraportal islet recipients vs. 10 normal controls and in seven portally-drained pancreas-kidney and eight nondiabetic kidney recipients vs. nine kidney donor controls. All transplant groups received comparable exposure to tacrolimus, and each transplant group was matched for kidney function to its respective control group.

INTERVENTION AND MAIN OUTCOME MEASURES:

All participants underwent glucose-potentiated arginine testing where acute insulin responses to arginine (5 g) were determined under fasting (AIR(arg)), 230 mg/dl (AIR(pot)), and 340 mg/dl (AIR(max)) clamp conditions, and AIR(max) gives the beta-cell secretory capacity. Insulin sensitivity (M/I) and proinsulin secretory ratios (PISRs) were assessed to determine whether tacrolimus increased beta-cell secretory demand.

RESULTS:

Insulin responses were significantly lower than normal in the islet group for AIR(arg) (P < 0.05), AIR(pot) (P < 0.01), and AIR(max) (P < 0.01), whereas responses in the pancreas-kidney and kidney transplant groups were not different than in the kidney donor group. M/I and PISRs were not different in any of the transplant vs. control groups.

CONCLUSIONS:

Impaired beta-cell secretory capacity in islet transplantation is best explained by a low engrafted beta-cell mass and not by a deleterious effect of tacrolimus.

PMID:
20097708
PMCID:
PMC2841536
DOI:
10.1210/jc.2009-2289
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center