title: Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes.
abstract: We examined the effect of rapamycin on the life span of a mouse model of type 2 diabetes, db/db mice. At 4 months of age, male and female C57BLKSJ-lepr (db/db) mice (db/db) were placed on either a control diet, lacking rapamycin or a diet containing rapamycin and maintained on these diets over their life span. Rapamycin was found to reduce the life span of the db/db mice. The median survival of male db/db mice fed the control and rapamycin diets was 349 and 302 days, respectively, and the median survival of female db/db mice fed the control and rapamycin diets was 487 and 411 days, respectively. Adjusting for gender differences, rapamycin increased the mortality risk 1.7-fold in both male and female db/db mice. End-of-life pathological data showed that suppurative inflammation was the main cause of death in the db/db mice, which is enhanced slightly by rapamycin treatment.
authors.affiliation: Department of Medicine.
authors.forename: Kavithalakshmi
authors.initials: K
authors.lastname: Sataranatarajan
authors.affiliation: Department of Pathology, and The Barshop Institute for Longevity and Aging Studies, University of Texas Health Sciences Center, San Antonio. Research Service and Geriatric Research and Education Center, Audie L. Murphy VA Hospital South Texas Veterans Health Care System, San Antonio.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.affiliation: Department of Pathology, and.
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.affiliation: Department of Medicine.
authors.forename: Denis
authors.initials: D
authors.lastname: Feliers
authors.affiliation: Department of Medicine.
authors.forename: Himabindu
authors.initials: H
authors.lastname: Yalamanchili
authors.affiliation: Department of Medicine.
authors.forename: Hak Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Medicine.
authors.forename: Meenalakshmi M
authors.initials: MM
authors.lastname: Mariappan
authors.affiliation: Department of Medicine.
authors.forename: Hooman
authors.initials: H
authors.lastname: Tabatabai-Mir
authors.affiliation: The Barshop Institute for Longevity and Aging Studies, University of Texas Health Sciences Center, San Antonio.
authors.forename: Vivian
authors.initials: V
authors.lastname: Diaz
authors.affiliation: Department of Medicine.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Medicine.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Javors
authors.affiliation: Department of Medicine, Research Service and Geriatric Research and Education Center, Audie L. Murphy VA Hospital South Texas Veterans Health Care System, San Antonio.
authors.forename: Goutam
authors.initials: G
authors.lastname: Ghosh Choudhury
authors.affiliation: Department of Pathology, and The Barshop Institute for Longevity and Aging Studies, University of Texas Health Sciences Center, San Antonio.
authors.forename: Gene B
authors.initials: GB
authors.lastname: Hubbard
authors.affiliation: Department of Medicine.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Barnes
authors.affiliation: ROCA/Department of Geriatric Medicine, University of Oklahoma Health Science Center and the Oklahoma City VA Medical Center. Arlan-richardson@ouhsc.edu.
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.affiliation: Department of Medicine, The Barshop Institute for Longevity and Aging Studies, University of Texas Health Sciences Center, San Antonio. Research Service and.
authors.forename: Balakuntalam S
authors.initials: BS
authors.lastname: Kasinath
mesh_terms: D000818:Animals; D002423:Cause of Death; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009026:Mortality; D012737:Sex Factors; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Life span; Obesity; Toxicity; mTOR Inhibition