Chronic rapamycin treatment causes diabetes in male mice

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 307, Issue 4, 2014, Pages

  Schindler, Christine E ^a   Partap, Uttara ^a   Patchen, Bonnie K ^a   Swoap, Steven J ^a  

^a WILLIAMS COLLEGE   (United States)

Author keywords

Diabetes; Estradiol; Hyperglycemia; Mammalian target of rapamycin; Rapamycin

Indexed keywords

ESTRADIOL; GLUCOSE; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN S6; RAPAMYCIN; SEX HORMONE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CASTRATED MALE; DIABETES MELLITUS; FEMALE; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE; GONADECTOMY; HEART; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; INSULIN SENSITIVITY; KIDNEY; MALE; MOUSE; NONHUMAN; OVARIECTOMY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SKELETAL MUSCLE; URINE;

DIABETES; ESTRADIOL; HYPERGLYCEMIA; MAMMALIAN TARGET OF RAPAMYCIN; RAPAMYCIN;

ADMINISTRATION, ORAL; ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS; ESTRADIOL; ESTROGEN REPLACEMENT THERAPY; FEMALE; GLUCOSE INTOLERANCE; GLYCOSURIA; MALE; MICE; ORCHIECTOMY; OVARIECTOMY; PANCREAS; PROTEIN KINASE INHIBITORS; PYRUVIC ACID; SEX FACTORS; SIROLIMUS; TESTOSTERONE; TIME FACTORS; TOR SERINE-THREONINE KINASES;

EID: 84907609211     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00123.2014     Document Type: Article

References (42)

1. Andersson B, Mattsson LA, Hahn L, Marin P, Lapidus L, Holm G, Bengtsson BA, Bjorntorp P. Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82: 638-643, 1997.
2. Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV. Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 10: 4230-4236, 2011.
3. Chang GR, Wu YY, Chiu Y.-S., Chen W.-Y., Liao J.-W., Hsu H.-M., Chao T.-H., Hung S.-W., Mao F.C. Long-term administration of rapamycin reduces adiposity, but impairs glucose tolerance in high-fat diet-fed KK/HlJ mice. Basic Clin Pharmacol Toxicol 105: 3, 2009.
4. Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Science Signal 2: ra75, 2009.
5. D'Souza DM, Al-Sajee D, Hawke TJ. Diabetic myopathy: impact of diabetes mellitus on skeletal muscle progenitor cells. Front Physiol 4: 379, 2013.
6. Dandona P, Dhindsa S. Hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab 96: 2643-2651, 2011.
7. Deblon N, Bourgoin L, Veyrat-Durebex C, Peyrou M, Vinciguerra M, Caillon A, Maeder C, Fournier M, Montet X, Rohner-Jeanrenaud F, Foti M. Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br J Pharmacol 165: 2325-2340, 2012.
8. Diamond MP, Grainger D, Diamond MC, Sherwin RS, Defronzo RA. Effects of methyltestosterone on insulin secretion and sensitivity in women. J Clin Endocrinol Metab 83: 4420-4425, 1998.
9. Dubal DB, Zhu H, Yu J, Rau SW, Shughrue PJ, Merchenthaler I, Kindy MS, Wise PM. Estrogen receptor α, not β, is a critical link in estradiol-mediated protection against brain injury. Proc Natl Acad Sci USA 98: 1952-1957, 2001.
10. Fang Y, Westbrook R, Hill C, Boparai RK, Arum O, Spong A, Wang F, Javors MA, Chen J, Sun LY, Bartke A. Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab 17: 456-462, 2013.
11. Favaro WJ, Cagnon VH. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate. Int J Exp Pathol 91: 537-545, 2010.
12. Fraenkel M, Ketzinel-Gilad M, Ariav Y, Pappo O, Karaca M, Castel J, Berthault MF, Magnan C, Cerasi E, Kaiser N, Leibowitz G. mTOR inhibition by rapamycin prevents β-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes 57: 945-957, 2008.
13. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460: 392-395, 2009.
14. Houde VP, Brule S, Festuccia WT, Blanchard PG, Bellmann K, Deshaies Y, Marette A. Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes 59: 1338-1348, 2010.
15. Hughes KJ, Kennedy BK. Cell biology. Rapamycin paradox resolved. Science 335: 1578-1579, 2012.
16. Johnston O, Rose CL, Webster AC, Gill JS. Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol 19: 1411-1418, 2008.
17. Jones TH. Effects of testosterone on Type 2 diabetes and components of the metabolic syndrome. J Diabetes 2: 146-156, 2010.
18. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14: 885-890, 2004.
19. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110: 163-175, 2002.
20. Lamming DW, Ye L, Astle CM, Baur JA, Sabatini DM, Harrison DE. Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive. Aging Cell 12: 712-718, 2013.
21. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335: 1638-1643, 2012.
22. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 149: 274-293, 2012.
23. Liu S, Navarro G, Mauvais-Jarvis F. Androgen excess produces systemic oxidative stress and predisposes to β-cell failure in female mice. PloS One 5: e11302, 2010.
24. Manrique C, Lastra G, Habibi J, Mugerfeld I, Garro M, Sowers JR. Loss of estrogen receptor α signaling leads to insulin resistance and obesity in young and adult female mice. Cardiorenal Med 2: 200-210, 2012.
25. Martel RR, Klicius J, Galet S. Inhibition of the immune response by rapamycin, a new antifungal antibiotic. Can J Physiol Pharmacol 55: 48-51, 1977.
26. Meshkani R, Saberi H, MohammadTaghvaei N, Tabatabaiefar MA. Estrogen receptor alpha gene polymorphisms are associated with type 2 diabetes and fasting glucose in male subjects. Mol Cell Biochem 359: 225-233, 2012.
27. Meyer MR, Clegg DJ, Prossnitz ER, Barton M. Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors. Acta Physiol (Oxf) 203: 259-269, 2011.
28. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van Roekel S, Winkleman L, Strong R. Rapamycinmediated lifespan increase in mice is dose and sex-dependent and appears metabolically distinct from dietary restriction. Aging Cell 13: 468-477, 2014.
29. Morrisett JD, Abdel-Fattah G, Hoogeveen R, Mitchell E, Ballantyne CM, Pownall HJ, Opekun AR, Jaffe JS, Oppermann S, Kahan BD. Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients. J Lipid Res 43: 1170-1180, 2002.
30. Paik S, Michelis M, Kim Y, Shin S. Induction of insulin-dependent diabetes by streptozotocin. Inhibition by estrogens and potentiation by androgens. Diabetes 31: 724-729, 1982.
31. Perline IH. An inexpensive mouse urine collection system. Physiol Behav 6: 597, 1971.
32. Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 137: 873-886, 2009.
33. Puddu A, Sanguineti R, Mach F, Dallegri F, Viviani GL, Montecucco F. Update on the protective molecular pathways improving pancreatic β-cell dysfunction. Mediators Inflamm 2013: 750540.
34. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 10 Suppl 4: 32-42, 2008.
35. Riant E, Waget A, Cogo H, Arnal JF, Burcelin R, Gourdy P. Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology 150: 2109-2117, 2009.
36. Stubbins RE, Holcomb VB, Hong J, Nunez NP. Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance. Eur J Nutr 51: 861-870, 2012.
37. Tataranni T, Biondi G, Cariello M, Mangino M, Colucci G, Rutigliano M, Ditonno P, Schena FP, Gesualdo L, Grandaliano G. Rapamycininduced hypophosphatemia and insulin resistance are associated with mTORC2 activation and Klotho expression. Am J Transplant 11: 1656-1664, 2011.
38. Teutonico A, Schena PF, Di Paolo S. Glucose metabolism in renal transplant recipients: effect of calcineurin inhibitor withdrawal and conversion to sirolimus. J Am Soc Nephrol 16: 3128-3135, 2005.
39. Tiano J, Mauvais-Jarvis F. Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes. Islets 4: 173-176, 2012.
40. Tiano JP, Delghingaro-Augusto V, Le May C, Liu S, Kaw MK, Khuder SS, Latour MG, Bhatt SA, Korach KS, Najjar SM, Prentki M, Mauvais-Jarvis F. Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents beta cell failure in rodent models of type 2 diabetes. J Clin Invest 121: 3331-3342, 2011.
41. Wang L, Kitano H, Hurn PD, Murphy SJ. Estradiol attenuates neuroprotective benefits of isoflurane preconditioning in ischemic mouse brain. J Cereb Blood Flow Metab 28: 1824-1834, 2008.
42. Yang SB, Lee HY, Young DM, Tien A.-C., Rowson-Baldwin A., Shu YY, Jan YN, Jan LY. Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J Mol Med 90: 575-585, 2012.