title: Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity.
abstract: Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent.
authors: Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, 1550, 4th Street, San Francisco, CA 94158, USA.
authors: Shi-Bing
authors: SB
authors: Yang
authors: Hye Young
authors: HY
authors: Lee
authors: David Matthew
authors: DM
authors: Young
authors: An-Chi
authors: AC
authors: Tien
authors: Ashley
authors: A
authors: Rowson-Baldwin
authors: Yu Yu
authors: YY
authors: Shu
authors: Yuh Nung
authors: YN
authors: Jan
authors: Lily Yeh
authors: LY
authors: Jan
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D018149:Glucose Intolerance / Q000150:complications / Q000473:pathology*; D006706:Homeostasis / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007328:Insulin; D005947:Glucose; D020123:Sirolimus