**4. Magnesium and gluconeogenesis**

Gluconeogenesis is the process of glucose synthesis from non-carbohydrate precursors. Phosphoenolpyruvate Carboxy kinase (PEPCK), fructose1,6-bisphosphatase (F1,6BP), pyru‐ vate carboxylase and glucose-6-phosphatase (G6Pase),catalyze irreversible reactions in the pathway and have lower activities compared to the other enzymes in the pathway and are thus considered rate limiting for glucose synthesis. Experiments by McNeill et al, [70] suggest that magnesium deficiency alters PEPCK by affecting secretion of pancreatic hormones. Of these four enzymes, Mg2+is required by three, that is, pyruvate carboxylase, PEPCK, and F1, 6BP reactions. Though hormones such as insulin, glucagon, glucocorticoids and epinephrine influence the key enzyme activities of gluconeogenic enzymes, Mg2+plays a role in the secretion of all these hormones [70]. Thus in Mg2+deficiency, enzyme activities may change, as a result of altered circulating levels of one or more hormones. In this study like in earlier studies, an increase in PEPCK activity was observed in magnesium deficient rats making Mg2+deficiency a possible contributing factor to the maintenance of low insulin levels an increased PEPCK in diabetes [70].

**Figure 2.** Graphic representations of the different glucose-related functions controlled by Mg2+in the hepatocyte.`

years to come.

In the case of liver cells, we have moved from the initial observation that Mg2+is abundantly represented within the hepatocyte as a whole to the notion that the cation's homeostasis is controlled by hormones, which promotes the movement of Mg2+in-and-out of the cell mem‐ brane to support and regulate specific liver metabolic functions. The observation that Mg2+is highly compartmentalized within cellular compartments and organelles support the notion that the cation plays a key role in regulating enzymes, channel activities, and metabolic processes within each of these organelles. Figure 2 recapitulates the relevance of Mg2+for the regulation of glucose homeostasis and bioenergetics within the hepatocyte. In the cytoplasm, Mg2+regulates glucokinase and glycolytic enzymes but also ATP utilization. In the mtiochon‐ dria, Mg2+regulates mitochondrial dehydrogenases and pyruvate dehydrogenase by promot‐ ing the activity of the pyruvate dehydrogenase phosphatase, responsible for dephosphorylating the enzyme to its active conformation. In the endoplasmic reticulum (ER), Mg2+regulates protein synthesis and the entry of glucose 6 phosphate (G6P), the limiting step for the utilization of this substrate by the glucose 6-phosphatase (G6Pase) and the hexose 6 phosphate dehydrogenase (H6PD), the reticular variant of the cytosolic glucose 6 phosphate dehydrogenase (G6PD). The oxidation of G6P by the H6PD generates high levels of NADPH within the ER lumen to be used for other metabolic processes within the organelle and in the rest of the cell, including fatty acid synthesis and cholesterol synthesis. Far from being complete, the picture is a dynamic scenario in need to further clarification and study in the

Role of Magnesium in the Regulation of Hepatic Glucose Homeostasis

http://dx.doi.org/10.5772/57564

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