Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnesium (Mg) makes up 0.5-1% of bone ash and is therefore not a trace element in the skeleton. Mg influences both mineral and matrix metabolism in bone by a combination of effects on hormones and other factors that regulate skeletal and mineral metabolism, and by direct effects on bone itself. The skeletal content of Mg is very variable both between and within species, and reported values range between 150 and 440 mmol/kg ash weight (AW). Dietary Mg has a direct influence and age an inverse influence on skeletal Mg content. It is unclear whether skeletal Mg content varies from region to region. In humans, reported values cluster around the 200 mmol/kg AW level, 30-40% lower than most rat data. Human iliac crest cortical bone has 10-20% less Mg per unit weight than iliac crest trabecular bone. Mg depletion adversely affects all phases of skeletal metabolism. In the rat, cessation of bone growth is noted with a decrease in both osteoblast and osteoblast activity, decreased bone formation, osteopenia, increased fragility and development of a form of 'aplastic bone disease'. The epiphyseal growth plate is thinned and the percent ash weight of the growth plate is increased, possibly due to enhanced crystallization of bone salt under conditions of Mg depletion. In contrast, in chicks and in rats with severe Mg deficiency, these 'antianabolic' effects are not observed but instead, predominant inhibition of bone resorption occurs with increased cortical thickness rather than osteopenia, and the occasional development of subperiosteal hyperplasia or of fibrous tumors of the periosteum. It is probable that this unusual response under conditions of severe Mg deficiency is in part an indirect effect secondary to a defect in secretion and/or skeletal responsiveness to parathyroid hormone (PTH) and vitamin D metabolites. Mg excess also has adverse biologic effects on bone. Crystallization of bone salt is severely impaired and an osteomalacia-like picture may be produced with decreased osteoblastic activity, widened growth plates, excessive osteoid seams and short, thickened bones. In some studies, especially in mice, Mg excess stimulates bone resorption, independently of PTH. The role of Mg deficiency and excess in human skeletal conditions requires more extensive investigation. Bone Mg is uniformly increased in renal insufficiency and may play a role in renal osteodystrophy since improvement has been noted in the osteomalacic component by normalizing the serum Mg. Decreased bone Mg has been reported in alcoholic patients, diabetes and in osteoporosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of magnesium on skeletal metabolism. 218 30

Magnesium may be important in the pathogenesis of coronary heart disease and sudden death. To study the role of magnesium, 400 high risk individuals were asked to volunteer either for a magnesium-rich diet (group A, 206) or for our usual diet (group B, 194) for 10 years in a randomized fashion. The age groups were between 25 and 63 years and the majority (374) of them were males. At entry to the study, age, sex, incidence of hypertension, diabetes, hypercholesterolemia, smoking, coronary disease and diuretic therapy were comparable. Dietary magnesium intake in group A (1,142 +/- 233 mg/day) was higher than in group B (418 +/- 105 mg/day). Total complications in group A (59; 28.6%) were significantly (p less than 0.001) less compared to group B (117; 60.3%). Sudden deaths were one and a half times more common in group B than in group A. Total mortality in group A (22; 10.7%) was significantly (p less than 0.01) less than in group B (34; 18.0%). A greater number of complications and increased mortality in group B subjects was consistent with a higher incidence of hypokalemia, hypomagnesemia and coronary risk factors in group B patients. Mean serum magnesium levels in group B participants were significantly (p less than 0.01) lowered compared to the mean magnesium level in group A participants who were administered the magnesium-rich diet. It is possible that increased intake of dietary magnesium in association with the general effects of a nutritious diet can offer protection against cardiovascular deaths among high-risk individuals predisposed to coronary heart disease.
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PMID:Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. 224 95

Magnesium is an important ion in all living cells being a cofactor of many enzymes, especially those utilising high energy phosphate bounds. The relationship between insulin and magnesium has been recently studied. In particular it has been shown that magnesium plays the role of a second messenger for insulin action; on the other hand, insulin itself has been demonstrated to be an important regulatory factor of intracellular magnesium accumulation. Conditions associated with insulin resistance, such as hypertension or aging, are also associated with low intracellular magnesium contents. In diabetes mellitus, it is suggested that low intracellular magnesium levels result from both increased urinary losses and insulin resistance. The extent to which such a low intracellular magnesium content contributes to the development of macro- and microangiopathy remains to be established. A reduced intracellular magnesium content might contribute to the impaired insulin response and action which occurs in Type 2 (non-insulin-dependent) diabetes mellitus. Chronic magnesium supplementation can contribute to an improvement in both islet Beta-cell response and insulin action in non-insulin-dependent diabetic subjects.
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PMID:Magnesium and glucose homeostasis. 225 26

Calmodulin is a substrate for insulin-receptor kinase obtained from rat adipocytes and hepatocytes and human placenta. In this study, we demonstrate that insulin stimulates the phosphorylation of calmodulin via insulin receptors partially purified from rat skeletal muscle. Phosphorylation of calmodulin was maximal in the presence of Mg2+ and insulin and the absence of Ca2+. Free-Ca2+ concentrations greater than 0.1 microM progressively inhibited phosphorylation with almost total inhibition at 200 microM Ca2+. Insulin-stimulated phosphorylation of calmodulin was dose dependent and saturable with half-maximal effect obtained at approximately 5 x 10(-10) M insulin. There was an absolute requirement for certain basic proteins, e.g., polylysine or protamine sulfate, to obtain phosphate incorporation into calmodulin. Polylysine stimulated the phosphorylation of calmodulin independently of insulin, but this was increased up to sixfold by the addition of insulin. Phosphate incorporation into calmodulin increased with increasing concentration of the substrate up to a saturating concentration of 2.4 microM. The Km for calmodulin was approximately 0.2 microM. Up to 0.15 mol of phosphate was incorporated per mole of calmodulin with tyrosine the predominant amino acid phosphorylated. The observations that calmodulin is phosphorylated by insulin-receptor kinase from all three classic target organs for insulin confirm that calmodulin is a general substrate for this kinase and suggest that Ca2+ and calmodulin may be components of the insulin-signaling mechanism.
Diabetes 1989 Jan
PMID:Calmodulin as substrate for insulin-receptor kinase. Phosphorylation by receptors from rat skeletal muscle. 253 26

Substrates of the insulin receptor tyrosine kinase have not been identified in skeletal muscle, a major target organ of insulin action. We observed the insulin-stimulated phosphorylation of a 195K protein (pp195) in extracts prepared from rat skeletal muscle and liver. pp195 copurifies with the insulin receptor on wheat germ agglutinin affinity chromatography. pp195 is not related to the insulin receptor, as assessed by lack of recognition by antinsulin receptor antibodies and by phosphopeptide mapping. Reduction of sulfhydryl bonds does not affect its apparent mol wt. Phosphorylation of pp195 has an absolute requirement in vitro for Mn2+ or Mg2+ and for certain basic poly-amino acids, i.e. poly-L-lysine or poly-L-ornithine. In the presence of 1 microM poly-L-lysine insulin stimulates pp195 phosphorylation in a dose-dependent manner (k0.5, approximately 5 x 10(-10) M; maximum approximately 10(-8) M insulin); pp195 phosphorylation by insulin-like growth factor-I requires about 100-fold higher doses. By phosphoamino acid analysis, pp195 is predominantly phosphorylated on tyrosine, and it is recognized by antiphosphotyrosine antibodies. Insulin receptors isolated from rat muscles 5 min after insulin injection induce about 2-fold greater phosphorylation of pp195 in vitro than receptors isolated from saline-injected controls. Streptozotocin-induced diabetes results in marked diminution of insulin-stimulated pp195 phosphorylation in extracts of muscle and liver (approximately 50% when normalized to protein content of wheat germ agglutinin eluates or approximately 80% reduction when normalized to equal receptor number). The defect is reversible by insulin therapy in vivo.
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PMID:Insulin-stimulated phosphorylation of a 195K protein from muscle and liver in the presence of poly-L-lysine. 254 86

Commercial Collagenase* prepared from Clostridium histolyticum is widely used in isolation of pancreatic islets. It is known that the enzyme is very impure and that there are substantial variations in effectiveness between batches. Our studies suggest that one of the impurities of importance in islet isolation is a protease that has not been very well characterized. Comparison of two batches of enzyme, one of which was known to give good yields of islets and the other poor yields, showed that they had very similar activity against collagen (measured by digestion of insoluble collagen followed by assay of soluble products with ninhydrin) but substantially different activities against azocasein as measured by optical density increase (measured by release of dye). Eighteen batches of Collagenase were examined for efficiency in islet isolation, and the yields obtained correlated with manufacturer's data of activity against casein. The data show that low caseinase activity is associated with performance in islet isolation (r = .5 after adjusting for collagenase activity). The effect of supplementing a batch of collagenase, known to be poor in isolating islets, with proteolytic enzymes was investigated. Trypsin and papain had apparently no effect, but dispase significantly increased yield. Dispase alone failed to digest pancreas. Size-exclusion high-performance liquid chromatography identified a peak associated with high protease activity and efficiency in islet isolation, having an Mr of approximately 30,000, compared to 78,000 for collagenase. The protease, like collagenase, is inhibited by EDTA. Increased Ca2+ and Mg2+ (up to 10 mM) did not affect activity. Both the protease and collagenase are stable under normal use but are inactivated by heating at 56 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jan
PMID:Protease activity in pancreatic islet isolation by enzymatic digestion. 264 34

The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 mumol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 mumol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.
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PMID:The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells. 267 93

A common complication of critically ill patients is cardiac tachyarrhythmia. The role played by magnesium is not well appreciated. Well-documented cases indicated that magnesium may be effective in controlling the rhythm when conventional methods fail. The following tachyarrhythmias respond favorably to magnesium: (1) intractable ventricular tachycardia and fibrillation, whether hypo- or normomagnesemic, (2) torsades de pointes, (3) digitalis-toxic ventricular tachyarrhythmia, (4) multifocal atrial tachycardia and (5) hypomagnesemic atrial tachyarrhythmia. It is recommended that 10-15 ml of 20% MgSO4 be infused over 1 min, followed by 500 ml of 2% MgSO4 over 5 h. A second 500 ml over 10 h may be necessary. Renal failure, disappearance of deep tendon reflex, rise in serum Mg above 5 mEq/l, drop in systolic blood pressure below 80 or drop in pulse below 60 contraindicate the continued use of magnesium. If serum potassium is at or falls below 4.0 mEq/l, 20-40 mEq/l KCl should be added. Magnesium deficiency can be confirmed by a low serum level or by a greater than 50% retention of administered magnesium. The causes of magnesium deficiency can be remembered under 10 DS: (1) Diarrhea and gastrointestinal losses, (2) Diuretics and renal losses, (3) Diabetes and endocrine causes, (4) Dietary lack, (5) Diverted to free fatty acids, (6) Drugs such as cisplatin, (7) Drinking alcohol to excess, (8) Delivery with toxemia, (9) Decompensated heart, lungs or liver and (10) Denuded skin, such as burns.
Magnesium 1989
PMID:Magnesium therapy of cardiac arrhythmias in critical-care medicine. 269 48

Diabetes is characterized by depressed cardiac functional properties attributed to Ca2+-activated ATPase activity. In contrast, endurance swimming enhances the cardiac functional properties and Ca2+-activated myofibril ATPase. Thus, the purpose of this study was to observe if the changes associated with experimental diabetes can be ameliorated with training. Diabetes was induced with a single i.v. injection of streptozotocin (60 mg/kg). Blood and urine glucose concentrations were 802 +/- 44 and 6965 +/- 617 mg/dL, respectively. The training control and training diabetic animals were made to swim (+/- 2% body weight) 4 days/week for 8 weeks. Cardiac myofibril, at 10 microM free Ca2+ concentration was reduced by 54% in the sedentary diabetics compared with sedentary control animals (p less than 0.05). Swim training enhanced the Ca2+-activated myofibril ATPase activities for the normal animals. The diabetic animals, which swam for 8 weeks, had further reduced their Ca2+-activated myofibril ATPase activity when compared with sedentary diabetics (p less than 0.05). Similarly, the Mg2+-stimulated myofibril ATPase activity was depressed by 31% in diabetics following endurance swimming. It is concluded that the depressed Ca2+-activated myofibril ATPase activity of diabetic hearts is not reversible with endurance swimming.
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PMID:Effect of endurance swimming on rat cardiac myofibrillar ATPase with experimental diabetes. 293 7

We investigated composite (total), Mg2+-(ouabain-resistant), and Na+-K+-(ouabain-inhibited) ATPase in sciatic nerves of diabetic mutant C57Bl/Ks (db/db) and age-related littermate (db/+) control mice at various ages (16, 26, and 40 wk). This is the first report indicating that nerve ATPase activities measured in vitro showed no deficit in mice with spontaneous diabetes. Thus, diabetic neuropathy in the genetically diabetic mouse may occur in the absence of Na+-K+-ATPase abnormalities, which were previously described in association with polyol pathway impairment in experimental diabetic and BB Wistar rats. Control and diabetic groups treated with ganglioside mixture for 30 days before death presented statistically insignificant differences. Therefore, the beneficial effect of gangliosides described in C57Bl/Ks (db/db) mice on electrophysiological and morphometrical parameters must be due to different pharmacological activities rather than to prevention of the decay or better maintenance of ATPase activity.
Diabetes 1987 Sep
PMID:Sciatic nerve ATPase activity is unaffected in diabetic mutant C57Bl/Ks (db/db) mice. 295 43


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