Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentrations of magnesium, potassium and zinc were determined in plasma, erythrocytes, muscle biopsies, and in urine collected during 24 hours, in 18 subjects with type II diabetes mellitus (DM). Magnesium was also determined in mononuclear cells. The results were compared with those in 35 (magnesium and potassium analyses) or 26 (zinc analyses) healthy controls. Subjects with type II DM had lower concentrations of magnesium (3.79 +/- 0.32 vs. 4.29 +/- 0.22 mmol/100 g FFDS), potassium (40.5 +/- 5.17 vs. 46.1 +/- 3.81 mmol/100 g FFDS) and zinc (231 +/- 29 vs. 247 +/- 23 ng/mg FFDS) in skeletal muscle. Furthermore, the urinary excretions of magnesium and zinc were higher, as compared with those in healthy controls (5.00 +/- 2.68 vs. 3.62 +/- 1.47 mmol/24 hours, and 683 +/- 285 vs. 326 +/- 205 micrograms/24 hours, respectively). The contents of magnesium, potassium and zinc plasma did not correlate with the corresponding concentrations in skeletal muscle or circulating blood cells, as investigated in healthy controls, diabetics and in all subjects together, implying that the plasma concentrations are not useful in the assessment of electrolyte status. Hence, deficiency of electrolytes frequently occurs, and should be looked for, in subjects with type II DM.
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PMID:Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. 320 15

To determine the effects of very-low-calorie diets on the metabolic abnormalities of diabetes and obesity, we have studied 10 obese, non-insulin-dependent diabetic (NIDDM) and 5 obese, nondiabetic subjects for 36 days on a metabolic ward during consumption of a liquid diet of 300 kcal/day with 30 g of protein. Rapid improvement occurred in the glycemic indices of the diabetic subjects, with mean (+/- SEM) fasting plasma glucose falling from 291 +/- 21 to 95 +/- 6 mg/dl (P less than 0.001) and total glycosylated hemoglobin from 13.1 +/- 0.7% to 8.8 +/- 0.3% (P less than 0.001) (normal reference range 5.5-8.5%). Lipid elevations were normalized with plasma triglycerides reduced to less than 100 mg/dl and total plasma cholesterol to less than 150 mg/dl in both groups. Hormonal and substrate responses were also comparable between groups with reductions in insulin and triiodothyronine and moderate elevations in blood and urinary ketoacid levels without a corresponding rise in free fatty acids. Electrolyte balance for sodium, potassium, calcium, and phosphorus was initially negative but approached equilibrium by completion of the study. Magnesium, in contrast, remained in positive balance in both groups throughout. Total nitrogen loss varied widely among all subjects, ranging from 70 to 367 g, and showed a strong positive correlation with initial lean body mass (N = 0.83, P less than 0.001) and total weight loss (N = 0.87, P less than 0.001). The nondiabetic group, which had a significantly greater initial body weight and lean body mass than the diabetic group, also had a significantly greater weight loss of 450 +/- 31 g/day compared with 308 +/- 19 g/day (P less than 0.01) in the diabetic subjects. The composition of the weight lost at completion was similar in both groups and ranged from 21.6% to 31.3% water, 3.9% to 7.8% protein, and 60.9% to 74.5% fat. The contribution of both water and protein progressively decreased and fat increased, resulting in unchanged caloric requirements during the diet. This study demonstrates that short-term treatment with a very-low-calorie diet in both obese diabetic and nondiabetic subjects results in: safe and effective weight loss associated with the normalization of elevated glucose and lipid levels, a large individual variability in total nitrogen loss determined principally by the initial lean body mass, and progressive increments in the contribution of fat to weight loss with stable caloric requirements and no evidence of a hypometabolic response.
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PMID:Metabolic consequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects. 351 Sep 22

The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Clinical studies with the NOVA ISE for IMg2+. 793 86

The plasma membrane enzyme (Ca2+ + Mg2+)-adenosine triphosphatase (ATPase) is hormonally regulated and may participate in Ca2+ signaling by removing excess Ca2+ from the cell. Therefore, observations of a hormone-specific loss of insulin stimulation of ATPase in kidney membranes from non-insulin-dependent diabetic (NIDDM) rats may reflect their insulin-resistant state. Consequently, to evaluate whether additional insulin-resistant conditions are associated with impaired function of ATPase and with loss of regulation of the enzyme by insulin, studies were extended to investigate (Ca2+ + Mg2+)-ATPase activities and hormonal regulation of the enzyme in kidney basolateral membranes from obese and lean Zucker rats. (Ca2+ + Mg2+)-ATPase activity was lower in membranes from obese rats compared with lean rats. Maximal velocity (Vmax) of the enzyme activity was 29.2 +/- 2.6 nmol Pi/mg/min in obese rats versus 57.2 +/- 6.5 in lean rats (P < .05). However, the affinity of the enzyme for Ca2+ was similar in obese and lean rats (Km Ca2+, 0.23 +/- 0.025 v 0.23 +/- 0.032 mumol/L Ca2+). Also, the Km for ATP of the enzyme was similar in membranes from obese and lean rats. Insulin, parathyroid hormone (PTH), and cyclic adenosine monophosphate (cAMP) stimulated the ATPase activity in membranes from lean rats in a dose-dependent manner (15% to 28%). Also, the protein kinase C (PKC) stimulator 12-O-tetradecanoyl phorbol-13-acetate (TPA) increased the ATPase activity in membranes from lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased activity of (Ca2+ + Mg2+)-adenosine triphosphatase (ATPase) and a hormone-specific defect in insulin regulation of ATPase in kidney basolateral membranes from obese fa/fa rats. 805 47

Ageing constitutes a risk factor for magnesium deficit. Primary magnesium deficit originates from two aetiological mechanisms: deficiency and depletion. Primary magnesium deficiency is due to insufficient magnesium intake. Dietary amounts of magnesium are marginal in the whole population whatever the age. Nutritional deficiencies are more pronounced in institutionalized than in free-living ageing groups. Primary magnesium depletion is due to dysregulation of factors controlling magnesium status: intestinal magnesium hypoabsorption, reduced magnesium bone uptake and mobilization, sometimes urinary leakage, hyperadrenoglucocorticism by decreased adaptability to stress, insulin resistance and adrenergic hyporeceptivity. Secondary magnesium deficit in ageing largely results from various pathologies and treatments common to elderly persons, i.e., non-insulin dependent diabetes mellitus and use of hypermagnesuric diuretics. Magnesium deficit may participate in the clinical pattern of ageing, particularly in neuromuscular, cardiovascular and renal symptomatologies. The consequences of hyperadrenoglucocorticism-the simplest marker of which is non-response to the dexamethasone suppression test-may include immunosuppression, muscle atrophy, centralization of fat mass, osteoporosis, hyperglycaemia, hyperlipidaemia, atherosclerosis, and disturbances of mood and mental performance through accelerated hippocampal ageing particularly. It seems very important to point out that magnesium deficit and stress aggravate each other in a true 'pathogenic vicious circle', particularly in the stressful state of ageing. The importance of magnesium deficit in the aetiologies of insulin resistance, and the adrenergic, osseous, oncogenic, immune and oxidant disturbances of ageing is still uncertain. Oral physiological magnesium supplementation (5 mg Mg/kg/d) is the best diagnostic tool for establishing the importance of magnesium deficiency. Too few open and double blind studies on the effects of the treatment of magnesium deficiency and of magnesium depletion in geriatric populations have been done. Further study is necessary to assess the true place of magnesium deficit in the pathophysiology of ageing.
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PMID:Magnesium and ageing. II. Clinical data: aetiological mechanisms and pathophysiological consequences of magnesium deficit in the elderly. 815 90

Association between insulin resistance and hypertension: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean young offspring and in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension as well as dyslipidemia, obesity and type 2 diabetes in a given subject. Pathogenetic mechanisms: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to dysbalance of vasoactive substances and/or raised cytosolic Ca2+) and/or a structural vasculopathy is a very important ultimate causative event. In the presumed mosaic of participating pressor mechanisms, distinct Na+ retention is almost obligatory with diabetes mellitus, while essential and particularly obesity-associated hypertension probably involves a tendency for sympathetic activation. Development of insulin resistance: Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or being overweight. Acute hyperinsulinemia on the one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, and it has been proposed that insulin resistance in certain transmembranous cation exchange systems may elevate cytosolic Ca2+. Nevertheless, whether insulin resistance and/or hyperinsulinemia itself contribute to the pathogenesis of hypertension is still unclear.
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PMID:Insulin resistance, hyperinsulinemia and hypertension. 815 79

The plasma membrane enzyme (Ca2+ + Mg2+)-adenosine triphosphatase [(Ca2+ + Mg2+)-ATPase] is hormonally regulated, and may participate in Ca2+ signaling by removing excess Ca2+ from the cell. Insulin increases ATPase activity in kidney cortical basolateral membranes (BLM) from normal rats, but fails to do so in membranes from insulin-resistant non-insulin-dependent diabetic (NIDDM) rats. To investigate mechanisms of insulin regulation of ATPase and to evaluate whether the loss of this regulation in diabetes is hormone-specific and depends on blood glucose levels, (Ca2+ + Mg2+)-ATPase function and its hormonal regulation were studied in kidney BLM from rats with mild and severe NIDDM. Km values for ATP and Ca2+ affinity of the ATPase were similar in diabetic and control rats, but the maximal velocity (Vmax) of the enzyme was higher in diabetic groups. Insulin, the protein kinase C (PKC) stimulator 12-0-tetradecanoylphorbol 13-acetate (TPA), parathyroid hormone (PTH), and cyclic adenosine monophosphate (cAMP) all increased the ATPase activity in BLM from controls by increasing the enzyme's affinity for Ca2+. A protein kinase A (PKA) inhibitor (H8 in low concentrations) abolished cAMP and PTH effects, but not those of insulin, whereas the PKC inhibitors (sphingosine and high concentrations of H8) did abolish the effects of insulin. Stimulations of ATPase activity by insulin and by PTH and cAMP were additive. Insulin and TPA lost their stimulatory effects on ATPase in BLM from rats with either mild or severe NIDDM, but PTH and cAMP maintained their stimulatory effects in these membranes. The data show [1] (Ca2+ + Mg2+)-ATPase activity is increased in NIDDM, and a hormone-specific loss of insulin stimulation of ATPase occurs; (2) these defects are not dependent on the level of glycemia; and (3) the stimulatory effects of insulin on the ATPase may be mediated in part via PKC. We suggest that the hormone-specific defect in insulin regulation of ATPase seen in the NIDDM rats may contribute to their insulin resistance.
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PMID:Hormone-specific defect in insulin regulation of (Ca2+ + Mg2+)-adenosine triphosphatase activity in kidney membranes from streptozocin non-insulin-dependent diabetic rats. 817 49

GENETIC PREDISPOSITION: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean, young offspring, as well as in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension together with dyslipidemia, obesity and type 2 diabetes in a given patient. INSULIN RESISTANCE AND HYPERINSULINEMIA AS SLOW PRESSOR MECHANISMS: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to an imbalance of vasoactive substances and/or raised cytosolic calcium) and/or structural vasculopathy is particularly important. Among the mosaic of assumed pressor mechanisms, distinct Na+ retention is almost invariably involved in diabetes mellitus, while sympathetic activation tends to occur in essential hypertension, particularly in association with obesity. Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or a decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or excess body weight. Acute hyperinsulinemia causes arterial vasodilation on one hand and increases sympathetic activity and renal Na+ reabsorption on the other. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, while insulin resistance may be associated with certain transmembraneous cation transporters, leading to an increase in cytosolic Ca2+. Hyperinsulinemia and/or insulin resistance may also be associated with an increased blood pressure sensitivity to high salt intake. In the mosaic of many different blood pressure-raising mechanisms, insulin resistance and/or hyperinsulinemia is likely to represent an amplifying slow or very slow pressor factor.
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PMID:Insulin resistance and hyperinsulinemia in hypertension. 857 90

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

Ageing constitutes a risk factor for magnesium deficit. Primary magnesium deficit originates from two etiological mechanisms: deficiency and depletion. Primary magnesium deficiency is due to insufficient magnesium intake. Dietary amounts of magnesium are marginal in the whole population whatever the age. Nutritional deficiencies are more pronounced in institutionalized than in free-living ageing groups. Primary magnesium depletion is due to dysregulation of factors controlling magnesium status: intestinal magnesium hypoabsorption, reduced magnesium bone uptake and mobilisation, sometimes urinary leakage, hyperadrenoglucocorticism by decreased adaptability to stress, insulin-resistance and adrenergic hyporeceptivity. Secondary magnesium deficit in ageing largely results from various pathologies and treatments common to elderly persons: i.e. non insulin dependent diabetes mellitus and use of hypermagnesuric diuretics. Magnesium deficit may participate in the clinical pattern of ageing: mainly neuromuscular, cardiovascular and renal symptomatologies. The consequences of hyperadrenoglucocorticism--whose non response to dexamethasone suppression test appears the simplest marker--may concern immunosuppression, muscle atrophy, centralization of fat mass, osteoporosis, hyperglycemia, hyperlipidemia, atherosclerosis, disturbances in mood and mental performances through accelerated hippocampal ageing particularly. Treatment of magnesium deficiency requires simple oral physiological magnesium supplementation. Treatment of the different types of magnesium depletion leads to a more or less specific control of pathophysiological disturbances of the required magnesium substrate. Open and double blind studies on the effects of the treatments of magnesium deficiency and of magnesium depletions in geriatic populations are too scarce. Further study is necessary to assess the accurate place of magnesium deficit in the physiopathology of ageing.
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PMID:Magnesium status and ageing: an update. 959 47


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