Change in glucose homeostasis in rats by long-term magnesium-deficient diet.
It is widely known that hypomagnesemia is one of the symptoms observed in diabetic patients. This study was performed to assess the effect of chronic magnesium (Mg) deficiency on glucose metabolism in rats. Male Sprague-Dawley rats (at the age of four weeks) were given a Mg-deficient diet or a control diet for two to eight weeks. The rats were orally administered sucrose solution (2 g/kg BW) every two weeks, and blood was drawn from a tail vein before and 15 min after sucrose loading to determine the concentrations of blood glucose and plasma insulin. At the same time, other rats in a non-fasted condition were sacrificed by decapitation (rats sacrificed at eight weeks were rats used for sucrose loading). The epididymal fat pads were immediately removed and adipocytes were isolated. The amount of glucose transporter 4 (GLUT4) in the plasma membranes and low-density microsomal membranes prepared from the adipocytes was measured by immunoblotting to estimate the influence of chronic Mg deficiency on glucose metabolism at the cellular level. In addition, plasma biochemical parameters and muscle mineral contents were also evaluated. The glucose concentration in fasted blood was significantly lower in Mg-deficient rats than in control rats throughout the experiment period. The feeding of a Mg-deficient diet also attenuated the response of blood glucose and plasma insulin: the glucose level in blood tended to be lower in Mg-deficient rats at 15 min after oral sucrose administration, and the difference was significant at two and eight weeks. The plasma insulin level in Mg-deficient rats was also lower, reaching a significant difference at two weeks. When animals were sacrificed in a non-fasted condition at 2-week intervals, the plasma glucose level was also significantly decreased in Mg-deficient rats as compared to control rats throughout the experiment period. The plasma insulin level in non-fasted Mg-deficient rats was also significantly decreased at two and six weeks. The Mg-deficient diet increased plasma triglyceride, but the difference was significant only at four weeks, and plasma cholesterol remained unchanged. The plasma Mg level was markedly lower in Mg-deficient rats throughout the experiment period. In Mg-deficient rats, the Mg content in muscle was significantly reduced at two and eight weeks, whereas the calcium and sodium contents were significantly increased throughout the experiment period. In Mg-deficient rats, the degree of translocation of GLUT4 to plasma membranes in the adipocytes stimulated by insulin was reduced only at eight weeks. In conclusion, since fasted and non-fasted blood glucose levels and the response of blood glucose to sucrose loading were decreased in Mg-deficient rats, it is suggested that Mg deficiency induces changes in the glucose metabolism via impaired glucose absorption in the intestine or an altered glucose uptake in the liver and/or peripheral tissues.
Kimura
Y
Y
Saga Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Murase
M
M
Nagata
Y
Y
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004032:Diet; D051275:Glucose Transporter Type 4; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D008274:Magnesium / Q000008:administration & dosage* / Q000378:metabolism; D008275:Magnesium Deficiency / Q000097:blood*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D013395:Sucrose; D008274:Magnesium