Hormonal
Inhibition of mTOR by rapamycin exacerbates metabolic dysfunction in type 2 diabetes by preventing beta-cell adaptation, inducing beta-cell apoptosis, and increasing insulin resistance.
Do not use mTOR inhibitors like rapamycin to treat type 2 diabetes. While these drugs may improve insulin sensitivity in muscle, they destroy pancreatic beta-cells and prevent the pancreas from adapting to high blood sugar, leading to severe worsening of diabetes.
Rapamycin induces fulminant diabetes by increasing insulin resistance and reducing beta-cell function and mass. These findings emphasize the essential role of mTOR/S6K1 in orchestrating beta-cell adaptation to hyperglycemia in type 2 diabetes. It is likely that treatments based on mTOR inhibition will cause exacerbation of diabetes.
Why this rating
Rigorous in vivo animal model with clear mechanistic pathways, though not directly translatable to human clinical trials without further validation.
Source
mTOR Inhibition by Rapamycin Prevents β-Cell Adaptation to Hyperglycemia and Exacerbates the Metabolic State in Type 2 Diabetes
Merav Fraenkel et al. · Diabetes · 2008
DOI 10.2337/db07-0922
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