Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes

Kavithalakshmi Sataranatarajan; Yuji Ikeno; Alex Bokov; Denis Feliers; Himabindu Yalamanchili; Hak Joo Lee; Meenalakshmi M. Mariappan; Hooman Tabatabai-Mir; Vivian Diaz; Sanjay Prasad; Martin A. Javors; Goutam Ghosh Choudhury; Gene B. Hubbard; Jeffrey L. Barnes; Arlan Richardson; Balakuntalam S. Kasinath

doi:10.1093/gerona/glv170

Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes

Kavithalakshmi Sataranatarajan, Yuji Ikeno, Alex Bokov, Denis Feliers, Himabindu Yalamanchili, Hak Joo Lee, Meenalakshmi M. Mariappan, Hooman Tabatabai-Mir, Vivian Diaz, Sanjay Prasad, Martin A. Javors, Goutam Ghosh Choudhury, Gene B. Hubbard, Jeffrey L. Barnes, Arlan Richardson, Balakuntalam S. Kasinath

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54 Scopus citations

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.

Original language	English (US)
Pages (from-to)	850-857
Number of pages	8
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	71
Issue number	7
DOIs	https://doi.org/10.1093/gerona/glv170
State	Published - Jul 2016

Keywords

Life span
Obesity
Toxicity
mTOR inhibition

ASJC Scopus subject areas

General Medicine

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10.1093/gerona/glv170

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Sataranatarajan, K., Ikeno, Y., Bokov, A., Feliers, D., Yalamanchili, H., Lee, H. J., Mariappan, M. M., Tabatabai-Mir, H., Diaz, V., Prasad, S., Javors, M. A., Choudhury, G. G., Hubbard, G. B., Barnes, J. L., Richardson, A., & Kasinath, B. S. (2016). Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 71(7), 850-857. https://doi.org/10.1093/gerona/glv170

Sataranatarajan, K, Ikeno, Y, Bokov, A, Feliers, D, Yalamanchili, H, Lee, HJ, Mariappan, MM, Tabatabai-Mir, H, Diaz, V, Prasad, S, Javors, MA, Choudhury, GG, Hubbard, GB, Barnes, JL, Richardson, A & Kasinath, BS 2016, 'Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 71, no. 7, pp. 850-857. https://doi.org/10.1093/gerona/glv170

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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-leprdb/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.",

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AU - Prasad, Sanjay

AU - Javors, Martin A.

AU - Choudhury, Goutam Ghosh

AU - Hubbard, Gene B.

AU - Barnes, Jeffrey L.

AU - Richardson, Arlan

AU - Kasinath, Balakuntalam S.

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Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes

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