Document Detail


Effect of tacrolimus dosing on glucose metabolism in an experimental rat model.
MedLine Citation:
PMID:  20877268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Maciej Malinowski; Johann Pratschke; Johan Lock; Peter Neuhaus; Martin Stockmann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of transplantation : quarterly of the Polish Transplantation Society     Volume:  15     ISSN:  1425-9524     ISO Abbreviation:  Ann. Transplant.     Publication Date:    2010 Jul-Sep
Date Detail:
Created Date:  2010-09-29     Completed Date:  2011-03-30     Revised Date:  2012-05-09    
Medline Journal Info:
Nlm Unique ID:  9802544     Medline TA:  Ann Transplant     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  60-5     Citation Subset:  IM    
Affiliation:
Department of General, Visceral, and Transplantation Surgery, University Hospital Charité, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / drug effects,  metabolism
Creatinine / blood
Diabetes Mellitus / drug therapy,  etiology,  physiopathology
Disease Models, Animal
Dose-Response Relationship, Drug
Glucose / metabolism*
Glucose Intolerance / complications,  drug therapy
Hypoglycemic Agents / metabolism,  therapeutic use
Immunosuppressive Agents / administration & dosage*
Insulin / metabolism*,  therapeutic use
Insulin-Secreting Cells / metabolism
Kidney Transplantation / adverse effects,  immunology,  physiology
Male
Rats
Rats, Wistar
Tacrolimus / administration & dosage*
Time Factors
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Hypoglycemic Agents; 0/Immunosuppressive Agents; 0/Insulin; 109581-93-3/Tacrolimus; 50-99-7/Glucose; 60-27-5/Creatinine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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