Magnesium deficiency and glucose metabolism in rat adipocytes.
We examined the effect of reducing ambient and intracellular free Mg ion ([Mg]i) concentrations on insulin action in epididymal adipocytes from male Sprague-Dawley rats in terms of (1) cellular transport of nonmetabolizable 2-deoxyglucose, (2) [U-14C]glucose oxidation to CO2, and (3) D-[3H]glucose incorporation into triglycerides. There were no significant differences in basal or insulin-stimulated transport of 2-deoxyglucose between adipocytes cultured in physiologic (1.24 mmol) or low (0.16 mmol) Mg for up to 24 hours. In contrast, insulin-stimulated but not basal [U-14C]glucose oxidation to CO2 was significantly reduced in adipocytes cultured in low versus physiologic Mg (P < .05 to .01). Similarly, there were no differences in basal glucose incorporation into triglycerides between cells cultured in low or physiologic Mg media for up to 24 hours. However, long-term (24-hour) but not short-term (2-hour) exposure of cells to low Mg was associated with a significant 30% reduction in insulin-stimulated D-[3H]glucose incorporation into triglycerides. When adipocytes incubated in low Mg were reincubated in high Mg (1.24 or 5 mmol) for 30 minutes, normal insulin-stimulated D-[3H]glucose incorporation into triglycerides was restored. Incubation of adipocytes in low Mg (0.16 mmol) for 24 hours resulted in a significant decrease in [Mg]i (264 +/- 89 v 437 +/- 125 micromol/cell [mean +/- SEM]) as compared with cells incubated in physiologic Mg (1.24 mmol; P < .01). These data support a role for intracellular Mg deficiency in the development of insulin resistance and suggest that the effect occurs at a site(s) distal to glucose entry into the cell. The effect of Mg deficiency on insulin action appears to be reversible.
Kandeel
F R
FR
Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, USA.
Balon
E
E
Scott
S
S
Nadler
J L
JL
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D002245:Carbon Dioxide / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism; D008275:Magnesium Deficiency / Q000150:complications / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000096:biosynthesis
D007328:Insulin; D014280:Triglycerides; D002245:Carbon Dioxide; D008274:Magnesium; D005947:Glucose