Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis.
Br J Pharmacol
; 172(15): 3793-804, 2015 Aug.
Article
in En
| MEDLINE
| ID: mdl-25884889
ABSTRACT
BACKGROUND AND PURPOSE:
Rapamycin, which is used clinically to treat graft rejection, has also been proposed to have an effect on metabolic syndrome; however, very little information is available on its effects in lean animals/humans. The purpose of this study was to characterize further the effects of the continuous use of rapamycin on glucose homeostasis in lean C57BL6/J mice. EXPERIMENTALAPPROACH:
Mice were fed a high-protein diet (HPD) for 12 weeks to develop a lean model and then were treated daily with rapamycin for 5 weeks while remaining on a HPD. Metabolic parameters, endocrine profiles, glucose tolerance tests, insulin sensitivity index, the expression of the glucose transporter GLUT4 and chromium distribution were measured in vivo. KEYRESULTS:
Lower body weight gain as well as a decreased caloric intake, fat pads, fatty liver scores, adipocyte size and glucose tolerance test values were observed in HPD-fed mice compared with mice fed a high-fat or standard diet. Despite these beneficial effects, rapamycin-treated lean mice showed greater glucose intolerance, reduced insulin sensitivity, lower muscle GLUT4 expression and changes in chromium levels in tissues even with high insulin levels. CONCLUSION AND IMPLICATIONS Our findings demonstrate that continuous rapamycin administration may lead to the development of diabetes syndrome, as it was found to induce hyperglycaemia and glucose intolerance in a lean animal model.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dietary Proteins
/
Sirolimus
/
Glucose
/
Homeostasis
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Br J Pharmacol
Year:
2015
Document type:
Article
Affiliation country:
Taiwán
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM