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

Ann Transplant. Jul-Sep 2010;15(3):60-5.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Creatinine / blood
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glucose / metabolism*
  • Glucose Intolerance / complications
  • Glucose Intolerance / drug therapy
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Immunosuppressive Agents / administration & dosage*
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Insulin-Secreting Cells / metabolism
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology
  • Male
  • Rats
  • Rats, Wistar
  • Tacrolimus / administration & dosage*
  • Time Factors

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Immunosuppressive Agents
  • Insulin
  • Creatinine
  • Glucose
  • Tacrolimus