β-Cell secretory capacity and demand in recipients of islet, pancreas, and kidney transplants
MR Rickels, R Mueller, KL Teff… - The Journal of Clinical …, 2010 - academic.oup.com
MR Rickels, R Mueller, KL Teff, A Naji
The Journal of Clinical Endocrinology & Metabolism, 2010•academic.oup.comContext: β-Cell secretory capacity, a measure of functional β-cell mass, is often impaired in
islet transplant recipients, likely because of a low engrafted β-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 β-
cell secretory capacity or with increased β-cell secretory demand independent of engrafted
islet mass. Design and Participants: We compared metabolic measures in five intraportal …
islet transplant recipients, likely because of a low engrafted β-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 β-
cell secretory capacity or with increased β-cell secretory demand independent of engrafted
islet mass. Design and Participants: We compared metabolic measures in five intraportal …
Abstract
Context: β-Cell secretory capacity, a measure of functional β-cell mass, is often impaired in islet transplant recipients, likely because of a low engrafted β-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 β-cell secretory capacity or with increased β-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 (AIRarg), 230 mg/dl (AIRpot), and 340 mg/dl (AIRmax) clamp conditions, and AIRmax gives the β-cell secretory capacity. Insulin sensitivity (M/I) and proinsulin secretory ratios (PISRs) were assessed to determine whether tacrolimus increased β-cell secretory demand.
Results: Insulin responses were significantly lower than normal in the islet group for AIRarg (P < 0.05), AIRpot (P < 0.01), and AIRmax (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 β-cell secretory capacity in islet transplantation is best explained by a low engrafted β-cell mass and not by a deleterious effect of tacrolimus.
Oxford University Press