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


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.
Malinowski
Maciej
M
Department of General, Visceral, and Transplantation Surgery, University Hospital Charité, Berlin, Germany.
Pratschke
Johann
J
Lock
Johan
J
Neuhaus
Peter
P
Stockmann
Martin
M
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D003404:Creatinine; D005947:Glucose; D016559:Tacrolimus