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)

The total activity of pyruvate dehydrogenase (PDH) complex in rat hind-limb muscle mitochondria was 76.4 units/g of mitochondrial protein. The proportion of complex in the active form was 34% (as isolated), 8-14% (incubation with respiratory substrates) and greater than 98% (incubation without respiratory substrates). Complex was also inactivated by ATP in the presence of oligomycin B and carbonyl cyanide m-chlorophenylhydrazone. Ca2+ (which activates PDH phosphatase) and pyruvate or dichloroacetate (which inhibit PDH kinase) each increased the concentration of active PDH complex in a concentration-dependent manner in mitochondria oxidizing 2-oxoglutarate/L-malate. Values giving half-maximal activation were 10 nM-Ca2+, 3 mM-pyruvate and 16 microM-dichloroacetate. Activation by Ca2+ was inhibited by Na+ and Mg2+. Mitochondria incubated with [32P]Pi/2-oxoglutarate/L-malate incorporated 32P into three phosphorylation sites in the alpha-chain of PDH; relative rates of phosphorylation were sites 1 greater than 2 greater than 3, and of dephosphorylation, sites 2 greater than 1 greater than 3. Starvation ( 48h ) or induction of alloxan-diabetes had no effect on the total activity of PDH complex in skeletal-muscle mitochondria, but each decreased the concentration of active complex in mitochondria oxidizing 2-oxoglutarate/L-malate and increased the concentrations of Ca2+, pyruvate or dichloracetate required for half-maximal reactivation. In extracts of mitochondria the activity of PDH kinase was increased 2-3-fold by 48 h starvation or alloxan-diabetes, but the activity of PDH phosphatase was unchanged.
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PMID:Reversible phosphorylation of pyruvate dehydrogenase in rat skeletal-muscle mitochondria. Effects of starvation and diabetes. 633 93

By adapting a standard method for precipitation of high-density lipoprotein cholesterol with phosphotungstic acid (PTA) and Mg2+, fetal pulmonary surfactant can be rapidly isolated from human amniotic fluid, 97% of the total disaturated phosphatidylcholine being precipitated from the sample. The lecithin/sphingomyelin ratio for 17 separate specimens correlated reasonably well (r = 0.76) with the concentration of disaturated phosphatidylcholine in the PTA precipitate. Using thiobarbituric acid as the chromophore, I measured sialic acid in the PTA precipitate after overnight treatment with neuraminidase. The sialic acid/protein ratio for the PTA precipitate was identical to that for the surfactant, as isolated by ultracentrifugation. The concentrations of insulin and C-peptide were significantly greater in specimens of amniotic fluid from mothers with diabetes than from non-diabetic mothers (p less than 0.001). When the specimens were segregated according to a C-peptide cutoff value of 4 micrograms/L, there was a small, significant decrease in PTA-precipitated concentrations of sialic acid in the samples with C-peptide greater than 4 micrograms/L. The results suggest a possible mechanism for the increased incidence of respiratory distress among infants born to diabetic mothers.
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PMID:A new technique for studying the relationship between maternal diabetes and the sialic acid content of fetal pulmonary surfactant. 638 29

In studies concerning risk factors for cardiovascular diseases, a number of reports have emphasized the influence of lipids, but the role of dietary minerals other than sodium has been less studied. However, epidemiological studies have suggested that dietary intake of magnesium and potassium may be involved in such pathogenesis. Studies of the influence of magnesium deficiency on arteriosclerosis include its effect on the initial lesion, altered metabolism of elastin, proliferation of collagen, calcification, lipid metabolism, platelet aggregation and hypertension. Magnesium and potassium metabolism are closely related and magnesium is required for maintaining the level of cellular potassium. As a consequence, magnesium and potassium deficiency frequently occur together and potassium deficiency may be an aggravating factor in pathogenesis. The development of the initial lesion in the arterial wall may be facilitated by loss of cellular magnesium and potassium. Experimental magnesium deficiency induces arterial damage, a loss of magnesium and potassium and an increase in the calcium and sodium content of the cell. Experimental models that have been used to produce cardiovascular lesions induce similar changes and losses of major intracellular cations may affect the main metabolic processes of the cell. This report summarizes the experimental evidence that magnesium deficiency may affect several different stages involved in arteriosclerosis and that potassium deficiency may exacerbate this. Magnesium deficiency results in vascular calcification. Experiments indicate that elastin is the site of the initial calcification and the metabolism of elastin is altered. This vascular lesion then brings about an increase in the collagen content of the wall. Low magnesium status could probably affect this process by slowing collagen resorption and lead to an irreversible accumulation of connective tissue. Results showing a different distribution of the various types of lipoprotein during experimental magnesium deficiency strongly suggest that lipid exchange between the vessel walls and blood can be modified. Severe magnesium deficiency in weanling rats produces a marked hypertriglyceridemia, a decrease in the percentage of cholesterol transported by HDL lipoprotein and a reduction in LCAT activity. The decreased clearance of circulatory triglycerides appears to be the major mechanism contributing to hyperlipemia. Magnesium deficiency could therefore contribute to accumulation of vascular lipid. Magnesium and potassium depletion have also been reported in diabetes and the vascular implications of this should be considered.(ABSTRACT TRUNCATED AT 400 WORDS)
Magnesium 1984
PMID:Role of magnesium and potassium in the pathogenesis of arteriosclerosis. 639 44

Diabetes mellitus is the most common pathological state in which secondary magnesium deficiency occurs. Magnesium metabolism abnormalities vary according to the multiple clinical forms of diabetes: plasma magnesium is more often decreased than red blood cell magnesium. Plasma Mg levels are correlated mainly with the severity of the diabetic state, glucose disposal and endogenous insulin secretion. Various mechanisms are involved in the induction of Mg depletion in diabetes mellitus, i.e. insulin and epinephrine secretion, modifications of the vitamin D metabolism, decrease of blood P, vitamin B6 and taurine levels, increase of vitamin B5, C and glutathione turnover, treatment with high levels of insulin and biguanides. K depletion in diabetes mellitus is well known. Some of its mechanisms are concomitant to those of Mg depletion. But their hierarchic importance is not the same: i.e., insulin hyposecretion is more important versus K+ than versus Mg2+. Insulin increases the cellular inflow of K+ more than that of Mg2+ because there is more free K+ (87%) than Mg2+ (30%) in the cell. The consequences of the double Mg-K depletion are either antagonistic: i.e. versus insulin secretion (increased by K+, decreased by Mg2+) or agonistic i.e. on the membrane: (i.e. Na+K+ATPase), tolerance of glucose oral load, renal disturbances. The real importance of these disorders in the diabetic condition is still poorly understood. Retinopathy and microangiopathy are correlated with the drop of plasma and red blood cell Mg. K deficiency increases the noxious cardiorenal effects of Mg deficiency. The treatment should primarily insure diabetic control.(ABSTRACT TRUNCATED AT 250 WORDS)
Magnesium 1984
PMID:Magnesium and potassium in diabetes and carbohydrate metabolism. Review of the present status and recent results. 639 45

Diabetes mellitus is associated with a decrease in bone mineral content and increased urinary excretion of calcium and phosphate. The purpose here was to elucidate the pathogenesis of these changes by comparing serum calcium fractions of diabetics and healthy controls. In a cross-sectional study, serum ionized calcium at pH 7.40, [Ca2+]7.4, of 46 insulin-treated diabetics was decreased in comparison with 44 healthy controls: mean 1.16 (SD 0.04) vs 1.21 (SD 0.03) mmol/L (p less than 0.001). The decreased [Ca2+]7.4 was associated with a higher concentration of complexed calcium in diabetic serum. The diabetics had higher concentrations of undetermined anions (p less tha 0.001) and this anion gap correlated negatively with [Ca2+]7.4 (r = -0.43, p less than 0.02). Serum [Mg2+] was decreased in the diabetics (p less than 0.001). Values for venous acid-base status, serum creatinine, total and ultrafiltrable calcium, parathyrin, and inorganic phosphate were the same in the two groups. [Ca2+]7.4, but not serum total calcium, had increased by 0.04 mmol/L (p less than 0.001) in the diabetics and by 0.02 mmol/L (p less than 0.01) in the controls by 90 min after breakfast, with and without subcutaneous insulin, respectively.
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PMID:Serum calcium fractions in diabetes mellitus. 675 97

The ionophore A23187 (10 micrograms/ml) did not affect the uptake of D-[U-14C]xylose by rat soleus muscle incubated under basal conditions. When muscles were incubated in a Ca2+/Mg2+-free (CMF) medium, A23187 promoted the efflux of intracellular Mg2+ and the efflux of 45Ca from preloaded muscles. Under these conditions, conditions, A23187 inhibited insulin-stimulated sugar transport without affecting 125I-insulin binding by the muscle. A23187 induced a slight fall in muscle ATP (16-18%); this does not appear to be responsible for the inhibitory effect of the ionophore on sugar transport. The inhibitory effect of A23187 was completely abolished when the CMF medium was supplemented with Mg2+ and partially reversed by Mn2+ or Zn2+; supplementation with Ca2+ did not reverse the inhibitory effect of the ionophore. These results suggest that insulin stimulates muscle sugar transport through a mechanism that involves intracellular Mg2+.
Diabetes 1982 Oct
PMID:Effect of ionophore A23187 on basal and insulin-stimulated sugar transport by rat soleus muscle. 681 67

In-vitro experiments are presented which indicate that the concentration of extracellular magnesium ions ([Mg2+]o) can exert profound influences on the contractility and reactivity of arteries, arterioles and veins from a number of regional vasculatures in several mammalian species, including man. Hypomagnesemia can potentiate the contractile activity of a variety of neurohumoral substances and induce vasospasm. Hypermagnesemia can do the reverse, i.e., induce hyporeactivity, relaxation and vasodilatation. Data are also presented to indicate that [Mg2+]o can control the entry, distribution and exit of calcium ions (Ca2+) from vascular smooth muscle cells. Arterial and venous smooth muscles excised from rats with alloxan-diabetes mellitus or spontaneous hypertension (SHR) appear to exhibit vascular membranes which have modifications in their Mg-Ca exchange sites. Data are reviewed which suggest that certain vascular diseases (e.g., sudden-death ischemic heart disease, hypertension, eclampsia, diabetes mellitus) are associated with a Mg-deficiency. Overall, it is suggested that [Mg2+]o and membrane [Mg] may play critical roles in regulating vascular tone and homeostasis.
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PMID:Hypomagnesemia and vasoconstriction: possible relationship to etiology of sudden death ischemic heart disease and hypertensive vascular diseases. 730 71

The properties and characteristics of acyl-CoA synthetase from the arterial wall of rats were investigated. The enzyme is located mainly in the microsomes. Its activity was found to be maximal at pH 7.0-8.0, and to be completely dependent on ATP, CoASH and Mg2+. The Km values for these substances were the same as those of the enzyme in liver. The activity was affected by serum, divalent cations, albumin, lipoproteins and phospholipids. In rats, the activity was decreased in various pathological conditions, such as tocopherol deficiency, hypertension and diabetes mellitus and was increased in hypercholesterolemia. The physiological significance of this enzyme in free fatty acid metabolism is discussed on the basis of these results.
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PMID:Studies on acyl-CoA synthetase in rat arterial wall. 745 88

Inhibition of insulin secretion by galanin is pertussis toxin (PTX) sensitive, suggesting the activation of one or more heterotrimeric (alpha, beta, gamma) G-proteins (Gi/Go). Multiple effectors, including the K+ATP and L-type Ca2+ channels, adenylyl cyclase, and an as yet unidentified system at a site close to exocytosis, are modulated by galanin. Therefore, it is necessary to delineate the particular G-proteins activated by the galanin receptor as a first step to understanding its net cellular response. During specific conditions, cholera toxin (CTX) can ADP-ribosylate the alpha i/alpha o-subunits of the PTX-sensitive substrates but only during receptor/G-protein interaction. Therefore, we used CTX-catalyzed ADP ribosylation to identify galanin receptor-associated G-protein alpha-subunits in RINm5F cells. Galanin enhanced the ADP ribosylation of membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in two bands at 39,000 and 42,000 M(r). This labeling was blocked in membranes prepared from PTX-treated cells, enhanced by Mg2+, and showed a biphasic dependence on exogenous guanine nucleotides. Identification of the CTX ADP-ribosylated G-proteins by immunoprecipitation with selective antisera indicate activation by the galanin receptor of alpha i1 and alpha i3, which have the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)). These studies provide evidence for the activation of multiple G-proteins by receptors for galanin in RINm5F cells.
Diabetes 1994 Jan
PMID:ADP ribosylation by cholera toxin identifies three G-proteins that are activated by the galanin receptor. Studies with RINm5F cell membranes. 750 45

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+ (4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p < 0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p < 0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.
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PMID:Effects of magnesium on platelet aggregation and adhesion. Magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo. 774 Apr 63


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