Tacrolimus reversibly reduces insulin secretion, induces insulin resistance, and causes islet cell damage in rats.
Int J Clin Pharmacol Ther
; 52(7): 620-7, 2014 Jul.
Article
in En
| MEDLINE
| ID: mdl-24755137
ABSTRACT
OBJECTIVE:
To investigate the diabetogenic effects of the immunosuppressive agent tacrolimus, the reversibility of these effects upon treatment discontinuation, and the underlying mechanisms in a rat model. MATERIALS ANDMETHODS:
60 healthy male rats were randomly divided into three groups for intragastric administration of tacrolimus either at 4 mg/kg/d or 2 mg/kg/d or an equal volume of normal saline (control). The treatment was administered for 5 months, followed by a 5-month period of no intervention. Fasting plasma glucose and insulin levels were used to calculate the homeostasis model assessment of ß-cell function (HOMA-ß) and insulin sensitivity index (ISI).RESULTS:
Tacrolimus treatment significantly increased blood glucose concentrations (p < 0.05) and lowered HOMA-ß and ISI (p < 0.01) in a time- and dose-dependent manner. Five months after tacrolimus treatment, significant islet cell injury was observed. However, 5 months after tacrolimus discontinuation, blood glucose concentrations significantly declined, HOMA-β and ISI levels significantly increased, and islet cell morphology noticeably improved.CONCLUSIONS:
In conclusion, tacrolimus treatment of healthy rats increased blood glucose concentrations in a time- and concentration-dependent manner. Development of tacrolimus-induced diabetes and reversibility after tacrolimus discontinuation may involve factors of and interactions between the insulin secretion pathway, local and/or systemic insulin resistance, and islet cell damage.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Islets of Langerhans
/
Tacrolimus
/
Immunosuppressive Agents
/
Insulin
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Clin Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2014
Document type:
Article