Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats

© 2020 Society for Endocrinology The kidneys release glucose into the systemic circulation through glucose reabsorption and renal gluconeogenesis. Currently, the significance of renal glucose release in pathological conditions has become a subject of interest. We examined the effect of sodium-depend...

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Main Authors: Myat Theingi Swe, Laongdao Thongnak, Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Anusorn Lungkaphin
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Published: 2020
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spelling th-cmuir.6653943832-702382020-10-14T08:42:47Z Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats Myat Theingi Swe Laongdao Thongnak Krit Jaikumkao Anchalee Pongchaidecha Varanuj Chatsudthipong Anusorn Lungkaphin Biochemistry, Genetics and Molecular Biology Medicine © 2020 Society for Endocrinology The kidneys release glucose into the systemic circulation through glucose reabsorption and renal gluconeogenesis. Currently, the significance of renal glucose release in pathological conditions has become a subject of interest. We examined the effect of sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i) on renal gluconeogenic enzyme expression in obese rats. Male Wistar rats (180-200 g) were fed either a normal diet (ND, n = 6) or a high-fat diet. At 16 weeks, after confirming the degree of glucose intolerance, high-fat diet-fed rats were randomly subdivided into three groups (n = 6/group): untreated group (HF), treated with dapagliflozin 1 mg/kg/day (HFSG) and treated with metformin 30 mg/kg/day (HFM). The treatment was continued for 4 weeks. We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats. Dapagliflozin downregulated the elevated expression of gluconeogenic transcription factors p-GSK3β, p-CREB and coactivator PGC1α in the renal cortical tissue. Metformin reduced the expression levels of renal cortical FOXO1 and CREB. Furthermore, reduced renal insulin signaling was improved and renal oxidative stress was attenuated by either dapagliflozin or metformin treatment in obese rats. We concluded that glucose tolerance was improved by dapagliflozin in obese prediabetic rats by suppressing renal glucose release from not only glucose reabsorption but also renal gluconeogenesis through improving renal cortical insulin signaling and oxidative stress. The efficacy of dapagliflozin in improving renal insulin signaling, oxidative stress and renal function was greater than that of metformin. 2020-10-14T08:26:00Z 2020-10-14T08:26:00Z 2020-05-01 Journal 14796805 00220795 2-s2.0-85082695400 10.1530/JOE-19-0480 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85082695400&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/70238
institution Chiang Mai University
building Chiang Mai University Library
continent Asia
country Thailand
Thailand
content_provider Chiang Mai University Library
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
Myat Theingi Swe
Laongdao Thongnak
Krit Jaikumkao
Anchalee Pongchaidecha
Varanuj Chatsudthipong
Anusorn Lungkaphin
Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
description © 2020 Society for Endocrinology The kidneys release glucose into the systemic circulation through glucose reabsorption and renal gluconeogenesis. Currently, the significance of renal glucose release in pathological conditions has become a subject of interest. We examined the effect of sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i) on renal gluconeogenic enzyme expression in obese rats. Male Wistar rats (180-200 g) were fed either a normal diet (ND, n = 6) or a high-fat diet. At 16 weeks, after confirming the degree of glucose intolerance, high-fat diet-fed rats were randomly subdivided into three groups (n = 6/group): untreated group (HF), treated with dapagliflozin 1 mg/kg/day (HFSG) and treated with metformin 30 mg/kg/day (HFM). The treatment was continued for 4 weeks. We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats. Dapagliflozin downregulated the elevated expression of gluconeogenic transcription factors p-GSK3β, p-CREB and coactivator PGC1α in the renal cortical tissue. Metformin reduced the expression levels of renal cortical FOXO1 and CREB. Furthermore, reduced renal insulin signaling was improved and renal oxidative stress was attenuated by either dapagliflozin or metformin treatment in obese rats. We concluded that glucose tolerance was improved by dapagliflozin in obese prediabetic rats by suppressing renal glucose release from not only glucose reabsorption but also renal gluconeogenesis through improving renal cortical insulin signaling and oxidative stress. The efficacy of dapagliflozin in improving renal insulin signaling, oxidative stress and renal function was greater than that of metformin.
format Journal
author Myat Theingi Swe
Laongdao Thongnak
Krit Jaikumkao
Anchalee Pongchaidecha
Varanuj Chatsudthipong
Anusorn Lungkaphin
author_facet Myat Theingi Swe
Laongdao Thongnak
Krit Jaikumkao
Anchalee Pongchaidecha
Varanuj Chatsudthipong
Anusorn Lungkaphin
author_sort Myat Theingi Swe
title Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
title_short Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
title_full Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
title_fullStr Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
title_full_unstemmed Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
title_sort dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats
publishDate 2020
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85082695400&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/70238
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