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


METHODS
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.


METHODS
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.
Rickels
Michael R
MR
University of Pennsylvania School of Medicine, 700 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6149, USA. rickels@mail.med.upenn.edu
Mueller
Rebecca
R
Teff
Karen L
KL
Naji
Ali
A
D000328:Adult; D000704:Analysis of Variance; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin; D005934:Glucagon; D001120:Arginine; D016559:Tacrolimus