Coadministration of sitagliptin or metformin has no major impact on the adverse metabolic outcomes induced by dexamethasone treatment in rats.

Autor: Figueiredo BS; Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil., Ferreira FBD; Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil., Barbosa AM; Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil., Dos Santos C; Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil., Ortsäter H; Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden., Rafacho A; Laboratory of Investigation in Chronic Diseases - LIDoC, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil; Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina - UFSC, Florianópolis, Brazil. Electronic address: alex.rafacho@ufsc.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Dec 01; Vol. 286, pp. 120026. Date of Electronic Publication: 2021 Oct 08.
DOI: 10.1016/j.lfs.2021.120026
Abstrakt: Aims: Glucocorticoids (GC) in excess cause glucose intolerance and dyslipidemia due to their diabetogenic actions. Conceptually, antidiabetic drugs should attenuate these side effects. Thus, we evaluated whether the coadministration of metformin or sitagliptin (or both) with dexamethasone could attenuate GC-induced adverse effects on metabolism.
Materials and Methods: Adult male rats were treated for 5 consecutive days with dexamethasone (1 mg/kg, body mass (bm), intraperitoneally). Additional groups were coadministered with metformin (300 mg/kg, bm, by oral gavage (og)) or sitagliptin (20 mg/kg, bm, og) or with both compounds in combination. The day after the last treatments, rats were submitted to glucose tolerance tests, pyruvate tolerance test, and euthanized for biometric, biochemical, morphologic, and molecular analyses.
Key Findings: Dexamethasone treatment resulted in reduced body mass and food intake, increased blood glucose and plasma insulin, dyslipidemia, glucose intolerance, pyruvate intolerance, and increased hepatic content of glycogen and fat. Sitagliptin coadministration improved glucose tolerance compared with the control group, an effect paralleled with higher levels of active GLP-1 during an oral GTT. Overall, sitagliptin or metformin coadministration did not prevent any of the dexamethasone-induced metabolic disturbances.
Significance: Coadministration of sitagliptin or metformin result in no major improvement of glucose and lipid metabolism altered by dexamethasone treatment in male adult rats.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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