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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Arginine / pharmacology
  • Blood Glucose / metabolism
  • Female
  • Glucagon / blood
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Insulin / blood
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans Transplantation / physiology*
  • Kidney Function Tests
  • Kidney Transplantation / physiology*
  • Male
  • Middle Aged
  • Pancreas Transplantation / physiology*
  • Tacrolimus / pharmacology


  • Blood Glucose
  • Immunosuppressive Agents
  • Insulin
  • Glucagon
  • Arginine
  • Tacrolimus