Investigation of the Effect of Magnesium Restriction on Glucose Transport in Schizosaccharomyces pombe

Abstract

Magnesium is vital for many biological processes such as energy metabolism, nucleic acid, and protein synthesis, signal transduction, and cell division. Impairment of magnesium homeostasis is associated with many diseases, especially cardiovascular diseases, hypertension, type 2 diabetes, and cancer. More than 300 million people worldwide struggle with type 2 diabetes, and this number is growing exponentially. Clinical studies have shown that serum magnesium levels were decreased in patients with type 2 diabetes and that magnesium supplementation has positive effects on glucose metabolism. In this study, glucose consumption and the expression level of glucose transporters (ght1, ght2, ght5) were investigated in magnesium transport-restricted model cell of Schizosaccharomyces pombe yeast, which is similar to mammalian cells in terms of biological processes and genetic mechanisms. In mutant strain with limited magnesium transport, glucose consumption increased due to the increase in magnesium added to the medium. The expression level of ght1, ght2, one of the glucose transporters, increased in 30 mM Mg2+ supplemented medium, decreased at higher magnesium concentration (75 mM), where optimum growth was observed for the strain, and there was no significant change in the expression level of ght5. Our findings indicate that the glucose transporters ght1 and ght2 are regulated by a different mechanism than ght5

Keywords

• magnesium deficiency
• glucose transport
• Schizosaccharomyces pombe

Schizosaccharomyces pombe’ de Magnezyum Kısıtlamasının Glukoz Transportu Üzerine Etkisinin Araştırılması

Abstract

Magnezyum, enerji metabolizması, nükleik asit ve protein sentezi, sinyal iletimi, hücre bölünmesi gibi birçok biyolojik süreç için hayati önem taşır. Magnezyum homeostasisinin bozulması, kardiyovasküler hastalıklar, hipertansiyon, tip 2 diyabet ve kanser başta olmak üzere çok sayıda hastalıkla ilişkilendirilmiştir. Dünya çapında 300 milyondan fazla insan tip 2 diyabet ile mücadele etmektedir ve bu sayı katlanarak artmaktadır. Klinik çalışmalar, tip 2 diyabetli hastalarda serum magnezyum seviyesinin düştüğünü ve magnezyum takviyesinin glukoz metabolizması üzerine olumlu etkileri olduğunu göstermiştir. Bu çalışmada, biyolojik süreçler ve genetik mekanizmalar bakımından memeli hücreleriyle benzerlik gösteren Schizosaccharomyces pombe mayasının magnezyum transportu kısıtlı mutant suşunda glukoz tüketimi ve glukoz taşıyıcılarının (ght1, ght2, ght5) anlatım seviyeleri araştırılmıştır. Magnezyum transportu kısıtlı olan mutant suşta, besi ortamına ilave edilen magnezyum artışına bağlı olarak glukoz tüketimi artmıştır. Glukoz taşıyıcılarından ght1, ght2 nin anlatım düzeyi, 30 mM Mg+2destekli ortamda artmış, suş için optimum üremenin görüldüğü daha yüksek magnezyum konsantrasyonunda (75 mM) azalmış, ght5’in anlatım düzeyinde ise anlamlı bir değişim bulunmamıştır. Bulgularımız, glukoz taşıyıcılarından ght1 ve ght2’ nin ght5’ ten farklı bir mekanizma ile düzenlendiğini işaret etmektedir.

Keywords

• magnezyum eksikliği
• glukoz transportu
• Schizosaccharomyces pombe

References

1. 1. Jahnen-Dechent, W. and Ketteler, M., Magnesium basics, CKJ: Clinical Kidney Journal, 2012. 5: p.3-14.
2. 2. De Baaij, J., Hoenderop, J. and Bindels, R., Magnesium in man: implications for health and disease, Physiol. Rev., 2015. 95: p.1-46.
3. 3. Fiorentini, D., et al., Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency, Nutrients, 2021.13(1136): p. 1-44.
4. 4. Pilchova, I., et al., The Involvement of Mg2+ in Regulation of Cellular and Mitochondrial Functions, Oxidative Medicine and Cellular Longevity, 2017. 6797460: p.1-8.
5. 5. Kostov, K., Effects of Magnesium Deficiency on Mechanisms of Insulin Resistance in Type 2 Diabetes: Focusing on the Processes of Insulin Secretion and Signaling, Int. J. Mol. Sci, 2019. (20)1351: p. 1-15.
6. 6. Guerrero-Romero, F., and Rodríguez-Morán, M.,Low serum magnesium levels and metabolic syndrome, Acta Diabetol 2002. 39: p. 209–213.
7. 7. Guerrero-Romero, F., et al., Hypomagnesaemia and risk for metabolic glucose disorders: a 10-year follow-up study, European journal of clinical investigation, 2008. 38(6): p. 389–396.
8. 8. Hruby, A.,et al., Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged americans. Diabetes care, 2014. 37 (2 ): p. 419-427.

9. 9. Mooren, F.C.,Magnesium and disturbances in carbohydrate metabolism, Diabetes, obesity & metabolism,2015. 17(9): p. 813–823.
10. 10. Barbagallo, M., et al., Serum ionized magnesium in diabetic older persons, Metabolism: clinical and experimental. 2014. 63(4): p. 502–509.
11. 11. Wälti, M.K., et al., Low plasma magnesium in type 2 diabetes, Swiss medical weekly, 2003. 133(19-20): p. 289–292.
12. 12. Lecube, A., et al., Diabetes is the main factor accounting for hypomagnesemia in obese subjects, PloS one, 2012. 7(1): p. 1-7.
13. 13. Chambers, E.C., et al., Serum Magnesium and Type-2 Diabetes in African Americans and Hispanics: A New York Cohort, Journal of the American College of Nutrition, 2006. 25(6): p. 509-513.
14. 14. Kığ, C., et al., Magnesium Deficiency Can Be a Sign for Predisposition to Diabetes, Yeni Yüzyıl Journal of Medical Sciences, 2020. 2:32-38.
15. 15. Nathan, D.M., et al., Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes, N. Engl. J. Med., 2005. 353: p.2643–2653.
16. 16. Svare, A.,A patient presenting with symptomatic hypomagnesemia caused by metformin-induced diarrhoea: a case report, Cases J, 2009. 2: p. 156.
17. 17. Paolisso, G., et al., Insulin induces opposite changes in plasma and erythrocyte magnesium concentrations in normal man, Diabetologia 1986. 29: p. 644-647.
18. 18. Song, Y., et al., Common genetic variants of the ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7), magnesium intake, and risk of type 2 diabetes in women, BMC medical genetics, 2009. 10: p. 4.
19. 19. Cam, H., and Whitehall, S., Analysis of heterochromatin in Schizosaccharomyces pombe, Cold Spring Harbor Protocols, 2016. 11: p. 920-927.
20. 20. Heiland, S., et al., Multiple hexose transporters of Schizosaccharomyces pombe, J Bacteriol, 2000. 182: p. 2153–2162.
21. 21. Saitoh, S., et al., Mechanisms of expression and translocation of major fission yeast glucose transporters regulated by CaMKK/phosphatases, nuclear shuttling, and TOR, Molecular biology of the cell, 2015. 26(2): p. 373–386.
22. 22. Matsuyama, A., et al., ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe, Nature biotechnology, 2006. 24(7): p. 841–847.
23. 23. Kim, D., et al., Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe, Nat Biotechnol, 2010. 12(1308): p. 617-623.
24. 24. Topal Sarikaya, A., Akman, G., and Temizkan, G., Nickel resistance in fission yeast associated with the magnesium transport system, Molecular Biotechnology, 2006. 32: p.139-145.
25. 25. Uz, G. and Topal Sarikaya, A.,The effect of magnesium on mitotic spindle formation in Schizosaccharomyces pombe, Genetics and Molecular Biology, 2016. 39(3): p.459-464.
26. 26. Bähler, J. and Wise, J., Preparation of total RNA from fission yeast, Cold Spring Harbor Protocols, 2017. : p. 306-310.
27. 27. Livak, K. and Schmittgen, T., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method, Methods, 2001. 25 (4): p. 402-408.
28. 28. Weisinger, J.R., and Bellorín-Font, E., Magnesium and phosphorus, Lancet, 1998. 352: p. 391-396.
29. 29. Rodríguez-Morán, M., and Guerrero-Romero, F., Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial, Diabetes Care, 2003. 26: p.1147–1152.
30. 30. Dong, J.Y., et al.,Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies, Diabetes Care, 2011. 34: p. 2116-2122.
31. 31. World Health Organization, Global report on diabetes, 2016.