ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2014
Chronic rapamycin treatment causes diabetes in male mice.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026Review
- Rapamycin Reverses the Hepatic Response to Diet-Induced Metabolic Stress That Is Amplified by Aging.Aging cell · 2026Article
- Review
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice.Aging cell · 2022Article
- Extending lifespan by modulating the growth hormone/insulin-like growth factor-1 axis: coming of age.Pituitary · 2021Review
- Intralacrimal Sustained Delivery of Rapamycin Shows Therapeutic Effects without Systemic Toxicity in a Mouse Model of Autoimmune Dacryoadenitis Characteristic of Sjögren's Syndrome.Biomacromolecules · 2021Article
- Health Effects of Alternate Day Fasting Versus Pair-Fed Caloric Restriction in Diet-Induced Obese C57Bl/6J Male Mice.Frontiers in physiology · 2021Article
- Fenofibrate rapidly decreases hepatic lipid and glycogen storage in neonatal mice with glycogen storage disease type Ia.Human molecular genetics · 2020Article
- The effect of a ketogenic diet and synergy with rapamycin in a mouse model of breast cancer.PloS one · 2020Article
- Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva.British journal of clinical pharmacology · 2019Review
- Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β-cells.Journal of cellular and molecular medicine · 2019Article
- Effect of rapamycin on bone mass and strength in the α2(I)-G610C mouse model of osteogenesis imperfecta.Journal of cellular and molecular medicine · 2019Article
- Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia.Human molecular genetics · 2019Article
- mTOR inhibitors for treatment of low-risk prostate cancer.Medical hypotheses · 2018Article
- β-Cell Autophagy in Diabetes Pathogenesis.Endocrinology · 2018Review
- Control of hyperglycemia in male mice by leflunomide: mechanisms of action.The Journal of endocrinology · 2018Article
- Article
- Preventative effects of resveratrol and estradiol on streptozotocin-induced diabetes in ovariectomized mice and the related mechanisms.PloS one · 2018Article
- Taming the Flames: Targeting White Adipose Tissue Browning in Hypermetabolic Conditions.Endocrine reviews · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Current evidence indicates that the mammalian target of rapamycin inhibitor rapamycin both increases longevity and, seemingly contradictorily, impairs glucose homeostasis. Most studies exploring the dimensions of this paradox have been based on rapamycin treatment in mice for up to 20 wk. We sought to better understand the metabolic effects of oral rapamycin over a substantially longer period of time in HET3 mice. We observed that treatment with rapamycin for 52 wk induced diabetes in male mice, characterized by hyperglycemia, significant urine glucose levels, and severe glucose and pyruvate intolerance. Glucose intolerance occurred in male mice by 4 wk on rapamycin and could be only partially reversed with cessation of rapamycin treatment. Female mice developed moderate glucose intolerance over 1 yr of rapamycin treatment, but not diabetes. The role of sex hormones in the differential development of diabetic symptoms in male and female mice was further explored. HET3 mice treated with rapamycin for 52 wk were gonadectomized and monitored over 10 wk. Castrated male mice remained glucose intolerant, while ovariectomized females developed significant glucose intolerance over the same time period. Subsequent replacement of 17β-estradiol (E2) in ovariectomized females promoted a recovery of glucose tolerance over a 4-wk period, suggesting the protective role of E2 against rapamycin-induced diabetes. These results indicate that 1) oral rapamycin treatment causes diabetes in male mice, 2) the diabetes is partially reversible with cessation of treatment, and 3) E2 plays a protective role against the development of rapamycin-induced diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.