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2016_24_Rovira_TxDirect.pdf (1.37 MB)

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2016-02-01

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cc-by-nc-nd (c) Rovira Juárez, Jordi et al., 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224589

mTOR Inhibition: Reduced Insulin Secretion and Sensitivity in a Rat Model of Metabolic Syndrome

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Recurs relacionat

https://doi.org/10.1097/TXD.0000000000000576

Resum

Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and ? -cell toxicity.Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test (IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, ?-cell proliferation, and apoptosis were analyzed at 12 days. Islets were isolated to analyze insulin content, insulin secretion, and gene expression.After 12 days, SRL treatment only impaired IPGTT in a dose-dependent manner in OZR. Treatment prolongation induced increase of area under the curve of IPGTT in LZR and OZR; however, in contrast to OZR, LZR normalized glucose levels after 2 hours. The SRL reduced pancreas weight and islet proliferation in LZR and OZR as well as insulin content. Insulin secretion was only affected in OZR. Islets from OZR + SRL rats presented a downregulation of Neurod1, Pax4, and Ins2 gene. Genes related with insulin secretion remained unchanged or upregulated.In conditions that require adaptive ? -cell proliferation, SRL might reveal harmful effects by blocking ? -cell proliferation, insulin production and secretion. These effects disappeared when removing the therapy.

Matèries

Receptors d'insulina, Complicacions de la diabetis, Regulació del metabolisme

Matèries (anglès)

Insulin receptors, Diabetes complications, Metabolic regulation

Citació

Col·leccions

Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

ROVIRA JUÁREZ, Jordi, et al. mTOR Inhibition: Reduced Insulin Secretion and Sensitivity in a Rat Model of Metabolic Syndrome. Transplantation Direct. 2016. Vol. 2, num. 2, pags. e65. ISSN 2373-8731. [consulted: 6 of August of 2026]. Available at: https://hdl.handle.net/2445/224589

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