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28 September 2010

Effect of tacrolimus dosing on glucose metabolism in an experimental rat model

Maciej Malinowski, Johann Pratschke, Johan Friso Lock, Peter Neuhaus, Martin Stockmann

Ann Transplant 2010; 15(3): 60-65 :: ID: 881167

Abstract

Background: Post-transplant diabetes mellitus (PTDM) is a serious complication after transplantation. The complex clinical situation makes it difficult to distinct influence of the single factors. To define impact of calcineurin inhibitor therapy on the PTDM after transplantation an experimental study analyzing the impact of different tacrolimus - dosages on the pancreatic beta-cell function was designed.
Material/Methods: Male Wistar rats received different doses of tacrolimus (0.1, 0.5, 1 and 10 mg/kg day) or tap water for 14 days. Serum glucose, insulin and creatinine levels were measured. Pancreas tissue was fixed in formaldehyde and stained with anti-insulin antibody. Staining intensity was assessed in a semiquantitive, blinded manner.
Results: There was no difference in the serum glucose and insulin levels between the tacrolimus treated and the control group. In the 10 mg/kg group the insulin amount in pancreas beta cells was significantly decreased, while the serum creatinine concentration was significantly increased. All other dosages showed no significant influence on function of insulin producing cells.
Conclusions: Tacrolimus in therapeutic dosages has no influence on the pancreas insulin production after 14 days of treatment. In contrast toxic tacrolimus dosages has a decreasing effect on insulin production, but is not associated with hypoinsulinemia. Only high doses of tacrolimus might induce glucose intolerance in transplanted patients.

Keywords: impaired glucose tolerance, Tacrolimus, Insulin, Islets of Langerhans

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358