title: Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.|Division of Residual Control, Agricultural Chemicals and Toxic Substance Research Institute, Council of Agriculture, Taichung, Taiwan.
authors.forename: Geng-Ruei
authors.initials: GR
authors.lastname: Chang
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Yi-Shin
authors.initials: YS
authors.lastname: Chiu
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.|Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Hou
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Frank Chiahung
authors.initials: FC
authors.lastname: Mao
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002857:Chromium / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology*; D002149:Energy Intake / Q000187:drug effects; D005234:Fatty Liver / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D004044:Dietary Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D002857:Chromium; D005947:Glucose; D020123:Sirolimus