glycogen and Magnesium-Deficiency

Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic β-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic β-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.

Topics: Blood Glucose; Calcium Channels, L-Type; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Progression; Glucokinase; Glycogen; Glycolysis; Humans; Inflammation; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; KATP Channels; Liver; Magnesium; Magnesium Deficiency; Obesity; Potassium Channels, Inwardly Rectifying; Sodium Chloride Symporters; Sodium-Potassium-Exchanging ATPase; Water-Electrolyte Imbalance

Electron-microscope studies of experimental models of myocardial ischaemia have provided basic information on the pathogenesis of hypoxic heart injury. Correlation of ultrastructural changes with biochemical data confirms the importance of catecholamine release and ionic shifts in the early evolution of ischaemic injury. An altered cellular metabolism induced by ischaemia causes rapid depletion of glycogen and is followed quickly by alterations in the nucleus, the mitochondria and the sarcotubular system; the myofibril is the organelle most resistant to hypoxia.Postmortem autolysis mimics early ischaemic change very closely and it probably has an initial hypoxic basis. Significant hypoxic-autolytic changes may begin during the agonal state. The time elapsing and the techniques of tissue preservation are critical in determining the amount of artefact. At present it is unrealistic to expect to obtain acutely ischaemic human myocardium soon enough after death to be of value in the estimation of the degree or duration of ischaemia by electron-microscope techniques. Rapidly progressive autolytic changes preclude the meaningful morphological assessment of hypoxic change at the ultrastructural level.

Topics: Animals; Cats; Coronary Disease; Disease Models, Animal; Dogs; Glycogen; Humans; Hypoxia; Magnesium Deficiency; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Organoids; Postmortem Changes; Rabbits; Rats

The effects of acute magnesium deficiency on lipid metabolism were examined in weaning rats fed a high carbohydrate diet containing starch or sucrose for 8 days. Rats were killed after the feeding period. In plasma, magnesium deficiency increased triglyceride and free cholesterol levels and decreased esterified cholesterol levels. Rats fed a magnesium-deficient diet containing sucrose showed particularly high triglyceride plasma levels. In liver, magnesium-deficient rats fed sucrose showed a significant increase in triglycerides, lactate and alpha-glycerophosphate and a significant decrease in glycogen. Changes in triglycerides and glycogen in the liver of magnesium-deficient rats fed starch were not significant. In sucrose-fed rats, serum lipoproteins were isolated by ultracentrifugation. With magnesium deficiency, triglycerides were significantly increased in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions and cholesterol levels were increased in the VLDL and LDL and significantly lower in the high density lipoprotein (HDL) fractions. The detrimental effect of severe magnesium deficiency associated particularly with a high carbohydrate diet content and more especially with a sucrose diet is discussed.

Topics: Animals; Cholesterol; Cholesterol Esters; Dietary Carbohydrates; Glycerophosphates; Glycogen; Lactates; Lactic Acid; Lipid Metabolism; Lipoproteins; Liver; Magnesium Deficiency; Male; Rats; Sucrose; Triglycerides