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Published on: November 16, 2011
Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis
Geng-Ruei Chang1,2, Yi-Shin Chiu1, Ying-Ying Wu1
1Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
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.
Experimental Approach:
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.
Key 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.
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.
Insights
Continuous rapamycin use in lean mice worsened glucose intolerance and insulin sensitivity. This suggests rapamycin may induce a diabetes syndrome, even in non-obese models.
Area of Science:
- Metabolic research
- Pharmacology
- Endocrinology
Background:
- Rapamycin is clinically used for graft rejection.
- Its metabolic effects, particularly in lean individuals, are poorly understood.
- Metabolic syndrome is a growing health concern.
Purpose of the Study:
- To investigate the impact of continuous rapamycin administration on glucose homeostasis.
- To characterize these effects specifically in lean C57BL6/J mice.
Main Methods:
- Lean mice were established using a high-protein diet (HPD).
- Mice received daily rapamycin treatment for five weeks while on HPD.
- Key metabolic parameters, glucose tolerance, insulin sensitivity, and GLUT4 expression were assessed.
Main Results:
- Rapamycin treatment in lean mice led to increased glucose intolerance and reduced insulin sensitivity.
- Muscle glucose transporter GLUT4 expression was decreased by rapamycin.
- Changes in tissue chromium levels were observed despite elevated insulin.
Conclusions:
- Continuous rapamycin administration can induce hyperglycemia and glucose intolerance.
- This suggests a potential risk of developing diabetes syndrome in lean individuals.
- Further research is needed to understand the mechanisms and clinical implications.
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