Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome

The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase se...

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Autores principales:	Hwee-Yeong Ng, Wei-Hung Kuo, You-Lin Tain, Foong-Fah Leung, Wen-Chin Lee, Chien-Te Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	dapagliflozin magnesium TRPM6 kidney Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/79f591184c54478c84ec887f2cb7a2bd
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spelling	oai:doaj.org-article:79f591184c54478c84ec887f2cb7a2bd2021-11-25T18:36:39ZEffect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome10.3390/nu131140882072-6643https://doaj.org/article/79f591184c54478c84ec887f2cb7a2bd2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4088https://doaj.org/toc/2072-6643The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.Hwee-Yeong NgWei-Hung KuoYou-Lin TainFoong-Fah LeungWen-Chin LeeChien-Te LeeMDPI AGarticledapagliflozinmagnesiumTRPM6kidneyNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4088, p 4088 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dapagliflozin magnesium TRPM6 kidney Nutrition. Foods and food supply TX341-641
spellingShingle	dapagliflozin magnesium TRPM6 kidney Nutrition. Foods and food supply TX341-641 Hwee-Yeong Ng Wei-Hung Kuo You-Lin Tain Foong-Fah Leung Wen-Chin Lee Chien-Te Lee Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome
description	The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.
format	article
author	Hwee-Yeong Ng Wei-Hung Kuo You-Lin Tain Foong-Fah Leung Wen-Chin Lee Chien-Te Lee
author_facet	Hwee-Yeong Ng Wei-Hung Kuo You-Lin Tain Foong-Fah Leung Wen-Chin Lee Chien-Te Lee
author_sort	Hwee-Yeong Ng
title	Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome
title_short	Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome
title_full	Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome
title_fullStr	Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome
title_full_unstemmed	Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome
title_sort	effect of dapagliflozin and magnesium supplementation on renal magnesium handling and magnesium homeostasis in metabolic syndrome
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/79f591184c54478c84ec887f2cb7a2bd
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Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome

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