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)

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

To elucidate the underlying mechanisms of platelet dysfunction in diabetes mellitus, we examined the activity of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-related signalling pathway, in platelets from NIDDM (non-insulin dependent diabetes mellitus) patients. The sGC activity was determined by measuring the amount of cyclic GMP produced in platelet cytosol. In the first study, we investigated the platelet sGC activity in untreated NIDDM patients without diabetic complications. In the male NIDDM patients, sodium nitroprusside (SNP) caused a significantly lower sGC response than that in age-matched control male subjects, while the enzyme activity of female diabetics did not differ from that in the controls. Secondly, we investigated effects of diabetic-associated factors on the enzyme activity in the male NIDDM patients. There was no difference in the SNP-stimulated sGC activity in platelets from male diabetics between with and without retinopathy. In the male diabetic patients with retinopathy, however, the platelet sGC activity was slightly increased by treatment with insulin. Interestingly, the changes in enzyme activity did not correlate with plasma glycosylated hemoglobin A1c levels in diabetic patients. The impairment of the NO-related signalling pathway may contribute to the platelet dysfunction observed in patients with diabetes mellitus.
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PMID:Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patients. 889 Sep 25

Incidence of essential hypertension has been reported to be significantly higher in the population afflicted with non-insulin dependent diabetes mellitus (NIDDM). The present studies were under taken in the insulin resistant, Zucker obese rats to evaluate various factors that could lead to the development of high blood pressure. Direct blood pressure measurements in the conscious obese rats indicated that they were not consistently hypertensive although the blood pressures of the obese rats tended to be higher than that of the control lean rats. However, after Inactin anesthesia blood pressures of the obese rats were significantly elevated which can be related to an increase in sympathetic tone since autonomic ganglionic blockade eliminated the differences between the pressures of the two groups. Under anesthesia, cardiac output per 100 gm body weight was significantly lower indicating inadequate tissue perfusion in the obese rats. In a separate series of studies carried out in conscious rats, reflexly mediated alterations in the heart rate to intravenous phenylephrine and sodium nitroprusside were significantly blunted in the obese rats. These observations which include enhanced central sympathetic discharge, inadequate systemic hemodynamics and attenuation of baroreceptor compensation collectively suggest that the insulin resistant obese rats are in a pre-hypertensive state and could develop sustained hypertension if they are exposed to other risk factors.
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PMID:Evaluation of hemodynamics, vascular reactivity and baroreceptor compensation in the insulin resistant Zucker obese rats. 892 47

N-Myristoyltransferase (NMT) catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of several proteins and are important in signal transduction. STZ-induced diabetes (an animal model for insulin-dependent diabetes mellitus, IDDM) resulted in a 2-fold increase in rat liver NMT activity as compared with control animals. In obese Zucker (fa/fa) rats (an animal model for non-insulin dependent diabetes mellitus, NIDDM) there was a approximately 4.7-fold lower liver particulate NMT activity as compared with the control lean rat livers. Administration of sodium orthovanadate to the diabetic rats normalised liver NMT activity. These results would indicate that the rat liver particulate N-myristoyltransferase activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation.
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PMID:In vivo modulation of N-myristoyltransferase activity by orthovanadate. 892 31

In vivo vanadate and vanadyl have been shown to mimic the action of insulin and to be effective treatment for animal models of both Type I and Type II diabetes. The molecular mechanism of action of the vanadium salts on insulin sensitivity remains uncertain, and several potential sites proposed for the insulin-like effects are reviewed. In human trials, insulin sensitivity improved in patients with NIDDM, as well as in some patients with IDDM after two weeks of treatment with sodium metavanadate. This increase in insulin sensitivity was primarily due to an increase in non-oxidative glucose disposal, whereas oxidative glucose disposal and both basal and insulin stimulated suppression of hepatic glucose output (HGP) were unchanged. Clinically, oral vanadate was associated with a small decrease in insulin requirements in IDDM subjects. Of additional benefit, there was a decrease in total cholesterol levels in both IDDM and NIDDM subjects. Furthermore, there was an increase in the basal activities of MAP and S6 kinases to levels similar to the insulin-stimulated levels in controls, but there was little or no further stimulation with insulin was seen. Further understanding of the mechanism of vanadium action may ultimately be useful in the design of drugs that improve glucose tolerance.
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PMID:In vivo and in vitro studies of vanadate in human and rodent diabetes mellitus. 892 42

We report four non-insulin-dependent diabetic (NIDDM) patients accompanied by a unique combination of sick sinus syndrome (SSS) and hyperinsulinemia of unknown etiology. SSS of all four cases was due to sinus arrest in association with paroxysmal atrial fibrillation (Rubenstein-III). Of special interest is that one patient showed a high prevalence of SSS and NIDDM among her close relatives. Hyperinsulinemia of moderate degree was seen at fasting state or after carbohydrate ingestion in the absence of obesity. The resistance to the action of insulin on glucose metabolism which was evaluated in three patients by the euglycemic hyperinsulinemic clamp study was found to be comparable to the lowest quartile level for common NIDDM patients. Because insulin is a physiological regulator of cell-membrane Na+/K+-ATPase, we speculate that malfunction of the sinus node automaticity may be caused by chronic exposure to hyperinsulinemia secondary to insulin resistance in these NIDDM patients.
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PMID:Association of sick sinus syndrome with hyperinsulinemia and insulin resistance in patients with non-insulin-dependent diabetes mellitus: report of four cases. 892 44

The aim of this study was to determine the ouabain receptor density, sodium content and contractile properties of skeletal muscles in rats with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus induced by streptozotocin treatment. These parameters were compared in isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of diabetic animals and their age-matched controls. Reversibility of the diabetes-induced changes was studied by insulin or thyroxine substitution. In IDDM SOL muscles both the maximum [3H]ouabain binding capacity (Bmax) and dissociation constant (Kd) were decreased, the sodium content of the muscles increased and the velocity of contraction and relaxation decreased. Similar changes (except for the reduction of Bmax) were observed in diabetic EDL muscles; however, in this case these differences were less prominent. All of these changes were reversed by insulin substitution, whereas thyroxine treatment normalized only the changes in Bmax and velocity of contraction. In contrast to the changes observed in IDDM, NIDDM increased both Kd and Bmax values. Linear correlation was observed between the velocity of contraction or relaxation and the density of [3H]ouabain binding sites in the SOL muscles of IDDM rats. It is concluded that IDDM and NIDDM induce opposite alterations in the density and ouabain sensitivity of the Na(+)-K+ pump in rat skeletal muscle. These diabetic changes are fully reversible with insulin substitution, they are variable in size according to the type of muscle, and are also reflected in the sodium content and, ultimately, in the contractile parameters of the muscles.
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PMID:Different [3H]ouabain binding characteristics of fast and slow skeletal muscles in IDDM and NIDDM diabetic rats. 893

The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I- octen-6-ynyl] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner 40 micrograms) and elastase (Elaszym 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.
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PMID:Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry. 894 5

Glomerular hyperfiltration and microalbuminuria are both regarded as risk factors for the development of diabetic nephropathy in insulin-dependent diabetic patients. Information on glomerular hyperfiltration is scarce in microalbuminuric non-insulin-dependent diabetic (NIDDM) patients. Therefore, we performed a cross-sectional study of glomerular filtration rate (single i.v. bolus injection of 51Cr-EDTA, plasma clearance for 4 h) in 158 microalbuminuric NIDDM patients compared to 39 normoalbuminuric NIDDM patients and 20 non-diabetic control subjects. The groups were well-matched with regard to sex, age and body mass index. The uncorrected (ml/min) and the adjusted (ml. min-1. 1.73 m-2) glomerular filtration rate were both clearly elevated in the microalbuminuric patients: 139 +/- 29 and 117 +/- 24 as compared to 115 +/- 19 and 99 +/- 15; 111 +/- 23 and 98 +/- 21 in normoalbuminuric NIDDM patients and control subjects, respectively (p < 0.001). The glomerular filtration rate (ml. min-1. 1.73 m-2) in NIDDM patients who had never received antihypertensive treatment was also clearly elevated in the microalbuminuric patients (n = 96): 119 +/- 22 as compared to 100 +/- 14 and 98 +/- 21 in normoalbuminuric NIDDM patients (n = 27) and control subjects (n = 20), respectively (p < 0.001). Glomerular hyperfiltration (elevation above mean glomerular filtration rate plus 2 SD in normoalbuminuric NIDDM patients) was demonstrated in 37 (95% confidence interval 30-45)% of the microalbuminuric patients. Multiple regression analysis revealed that HbA1c, 24-h urinary sodium excretion, age and known duration of diabetes were correlated with glomerular filtration rate in microalbuminuric NIDDM patients (r2 = 0.21, p < 0.01). Our cross-sectional study indicates that NIDDM patients at high risk of developing diabetic nephropathy are also characterized by an additional putative risk factor for progression, glomerular hyperfiltration.
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PMID:Glomerular hyperfiltration in microalbuminuric NIDDM patients. 896 Aug 46

In order to determine the involvement of denervation in endothelium-independent, nitric oxide (NO)-dependent smooth muscle vasodilation, we have measured vascular endothelial and smooth muscle function in three groups of age- and sex-matched patients: 8 patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) with neuropathy; 7 NIDDM patients without neuropathy; and 10 non-diabetic control subjects. Laser Doppler probes were used to measure blood flow in the dorsum of the left foot. Vascular endothelial response was assessed by measuring vasodilatory responses to iontophoretic application of acetylcholine to the dorsum of the foot. Vascular smooth muscle activity was assessed by the response to iontophoresis of sodium nitroprusside (SNP)-a NO donor and direct vasodilator. The vasodilator response to acetylcholine, expressed as the ratio of peak to basal blood flow, was significantly reduced in both diabetic groups when compared to non-diabetic controls (geometric mean x/divided by anti-logged SD 9.81 x/divided by 1.65 versus patients with neuropathy 3.50 x/divided by 2.03, p < 0.005 and diabetic non-neuropathic subjects 3.49 x/divided by 1.67, p < 0.005). The difference between the two groups of diabetic patients was not significant. In contrast, the vasodilatation to nitroprusside was significantly reduced only in the diabetic neuropathic patients, significantly lower than in either the non-neuropathic diabetic controls or the non-diabetic controls (2.1 x/divided by 2.0 versus 6.42 x/divided by 1.56 and 7.02 x/divided by 2.05, p < 0.005). This indicates that neuropathy is important in abnormalities of endothelium-independent vasodilatation.
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PMID:NO-dependent smooth muscle vasodilatation is reduced in NIDDM patients with peripheral sensory neuropathy. 911 81


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