Metabolic Syndrome, a pathological condition affecting approximately 35% of the USA population, is characterized by obesity, insulin resistance, and hypertension. Metabolic syndrome is considered the single most common condition predisposing to the development of various chronic diseases including diabetes and hypertension. Hypomagnesaemia has been consistently observed in association with metabolic syndrome, but it is unclear whether reduced Mg2+ levels are the consequence or a possible cause for the development of the metabolic syndrome and/or its associated pathologies. Research performed in our laboratory showed that rats exposed for 2 weeks to a Mg2+ deficient diet presented decreased glucose accumulation into the hepatocytes together with low Mg2+ level in the circulation and within the liver cells. To better investigate the changes in glucose metabolism, HepG2 were used to mimic in vitro Mg2+ deficiency conditions. HepG2 cells cultured in low extracellular Mg2+ presented a 20% decrease in total cellular Mg2+ content, reduced glucose accumulation, and enhanced glucose 6-phosphate (G6P) transport into the endoplasmic reticulum (ER). The increased G6P transport was associated with its enhanced hydrolysis by the glucose 6-phosphatase, but also conversion to 6-phosphogluconolactone by the glucose 6-phosphate dehydrogenase. The latter process resulted in the increased generation of NADPH within the ER and the increased conversion of cortisone to cortisol by the 11-β-hydroxysteroid dehydrogenase type-1 (11-β-OHSD1). Taken together, our results provide compelling evidence that Mg2+ deficiency precedes and actually promotes some of the hepatic dysmetabolisms typical of the metabolic syndrome. The decrease in intrahepatic Mg2+ content up-regulates G6P entry into the hepatic endoplasmic reticulum and its routing into the pentose shunt pathway for energetic purposes. The associated increased in NADPH production within the ER then stimulates cortisol production, setting the conditions for hepatic insulin resistance and further altering liver metabolism.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.