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 effect of ganglioside administration to nondiabetic and streptozocin-induced diabetic rats on sciatic nerve Na(+)-K(+)-ATPase, polyphosphoinositide (PPI) turnover, and protein phosphorylation was investigated. Gangliosides were injected (10 mg/kg body wt i.p.) for 10 or 30 days beginning 20 days after induction of diabetes. Na(+)-K(+)-ATPase activity was reduced nearly 50% in diabetic nerve and was restored to normal by both ganglioside treatments. The elevated levels of fructose and sorbitol and depressed content of myoinositol in diabetic nerve were unaffected by 30 days of ganglioside treatment, indicating that the restoration of Na(+)-K(+)-ATPase activity is not dependent on normal concentrations of these compounds. In the same nerves, 32P incorporation into phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate increased 73-76 and 39-53%, respectively, in diabetic compared with nondiabetic tissue. Ganglioside administration abolished the elevated labeling of PPIs after 30 days but was ineffective after only 10 days. Neither ganglioside regimen was able to reverse enhanced phosphorylation of the major peripheral nerve myelin protein P0. The finding that gangliosides can more quickly correct the effects of diabetes on Na(+)-K(+)-ATPase activity than on PPI turnover suggests that the mechanisms underlying these two phenomena are not closely related and are distinct from the sequence of events responsible for altered myelin protein phosphorylation.
Diabetes 1990 Jul
PMID:Correction of altered metabolic activities in sciatic nerves of streptozocin-induced diabetic rats. Effect of ganglioside treatment. 216 1

Platelet intracellular Ca2+ concentration ([Ca2+]i) and its response to stimuli (ADP and thrombin) were studied in 15 insulin-dependent and 22 non-insulin-dependent diabetes mellitus patients with the fluorescent probe Fura 2. The activity of Ca2(+)-ATPase and Na(+)-K(+)-ATPase, membrane fluidity, and cholesterol and phospholipid content were also determined in platelet membranes. Compared with control subjects, diabetic patients showed 1) increased platelet [Ca2+]i in the resting state, 2) higher Ca2+ levels after stimulation with thrombin and ADP, due entirely to increased resting concentrations, 3) reduced activity of Na(+)-K(+)-ATPase, 4) increased activity of Ca2(+)-ATPase, 5) higher fluidity of the platelet membrane, and 6) increased membrane concentration of total phospholipids. Na(+)-K(+)-ATPase activity was inversely related to platelet [Ca2+]i in each group studied, whereas Ca2(+)-ATPase activity was positively correlated with intracellular Ca2+ levels. The data obtained in diabetic subjects suggest an abnormality in Ca2+ and Na+ transport across the platelet membrane that might be responsible for the reported platelet hyperreactivity to stimuli in diabetes.
Diabetes 1990 Jul
PMID:Altered cellular Ca2+ and Na+ transport in diabetes mellitus. 216 3

The levels of mRNAs encoding the alpha 1 chain of collagen IV and the B1 chain of laminin were assayed in the lenses and retinas of long-term (28-week) diabetic and galactosaemic rats in order to gain some insight into the effects on basement membrane (BM) synthesis in these tissues. mRNAs coding for beta-actin, glucose transporter protein and the alpha 2 catalytic subunit of Na+,K(+)-ATPase were also assayed to determine whether any effects on BM-coding mRNA levels were specific. Long-term diabetes had no significant effect on the levels of alpha 1 (IV) collagen mRNA but caused a significant reduction in the laminin B1 message in the lens. In the same samples, the level of the glucose transporter protein mRNA was found to be elevated significantly in the diabetic tissue, whereas the mRNAsen coding beta-actin and alpha 2 Na+,K(+)-ATPase were unaffected in comparison with age-matched controls. Long-term galactosaemia resulted in significant increases in the levels of all mRNAs assayed when expressed per micrograms total RNA used for each analysis. However, this effect appeared to be due to a specific loss of ribosomal RNA from these severely cataractous lenses. When related to the beta-actin mRNA internal control, the levels of mRNA in the galactosaemic lenses were very similar to that found in the diabetics. Laminin B1 mRNA levels were decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of long-term diabetes and galactosaemia upon lens and retinal mRNA levels in the rat. 216 48

The activity of Na-K-ATPase in the kidney is increased by experimental diabetes. Because the kidney is rich in myo-inositol and abnormal inositol metabolism has been implicated in early neural complications of diabetes, we studied the effect of myo-inositol supplementation on Na-K-ATPase activity in renal medullary and cortical homogenates of Sprague-Dawley rats made diabetic with streptozotocin. Myo-inositol (650 mg/kg) was administered by gavage daily for 1 and 2 weeks after induction of diabetes. Medullary Na-K-ATPase (mumol/mg protein/h) was increased at 1 week by approximately 60% in diabetic rats versus control (25.9 +/- 0.07 vs 16.3 +/- 0.7; P less than .01). This increase was completely prevented by myo-inositol supplementation, despite persistent hyperglycemia. At 2 weeks, similar results were seen; medullary Na-K-ATPase activity was increased by 50% in diabetic rats compared with control, and once again myo-inositol prevented this increase. Sorbinil, the aldose reductase inhibitor, was also administered by gavage (20 mg/kg) for 2 weeks and partially prevented the increase in medullary Na-K-ATPase activity (20.0 +/- 0.9; P less than .05). At both 7 and 14 days, Na-K-ATPase activity in the cortex of untreated diabetic rats was also significantly increased compared with nondiabetic control rats and the increase was prevented by myo-inositol or Sorbinil. Myo-inositol or Sorbinil did not reduce Na-K-ATPase activity of nondiabetic control rats, nor did they prevent the increase in medullary Na-K-ATPase in compensatory hypertrophy following uninephrectomy. Myo-inositol content of outer medulla was about five to six times that of cortex, but was unaltered by the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of myo-inositol on renal Na-K-ATPase in experimental diabetes. 217 Aug 18

This study showed that steady-state kinetics of ATP hydrolysis by Na(+)-K(+)-ATPase are altered in the BB Wistar diabetic rat and experimental galactosemia. Four days after onset, this change was not evident if NaCNBH3 was omitted during enzyme preparations (indicating reversibility). Ninety days after onset, NaCNBH3 reduction was not necessary to see the change in ATP hydrolysis kinetics (indicating nonreversibility). The change in steady-state ATP hydrolysis was similar to that reported earlier for Na(+)-K(+)-ATPase of the lens epithelium and kidney medulla of diabetic individuals and for two in vitro glycosylation models. Our study also showed that the affinities of Na(+)-K(+)-ATPase for K+ are altered, and Na(+)-K(+)-ATPase-dependent K+ occlusion is inhibited in diabetic and galactosemic animals. Because K+ occlusion is required for efficient K+ transport, this finding supports previous in vitro studies that indicated that glycosylation inhibits pump-dependent K+ transport. Furthermore, our study suggested an irreversible impairment of Na(+)-K(+)-ATPase function in the diabetic BB Wistar rat as early as 15 days after onset, even when blood glucose was maintained at 6.7 mM by daily insulin injection.
Diabetes 1990 Dec
PMID:Na(+)-K(+)-ATPase and changes in ATP hydrolysis, monovalent cation affinity, and K+ occlusion in diabetic and galactosemic rats. 217 7

Obesity is known to be associated with diabetes, hypertension and hyperlipidemia in the majority of the patients. There could be inaccuracy in measuring the blood pressure in obesity, therefore a cuff of sufficient size is important in blood pressure measurement. All parameters of obesity have been found to have a correlation with hypertension and it has been suggested that change in weight would cause a change in blood pressure. A weight reduction of 12 kg results in a blood pressure fall of 21/13 mm Hg. Such changes in blood pressures have been noted in untreated hypertensives. A few studies have negated the role of change in weight to have any influence on hypertension. Obesity causes a higher cardiac output and higher blood volume leading to hypertension. There may be increased intracellular sodium and reduced sodium-potassium-ATPase activity in obesity which causes increased sodium loading in hypertension. Abnormalities related to the insulin-carbohydrate metabolism and the renin-angiotensin aldosteron system have also been demonstrated in obese patients. Weight reduction also causes reduced dietary salt intake and diminished sympathetic activity. The benefits of weight reduction appear to be directly related to the amount of weight lost.
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PMID:Effect of obesity and weight reduction in hypertension. 218 Feb 41

Intestinal amino acid and glucose transport is increased in various disease states and physiological circumstances. This enhancement is generally due to an increase in transport capacity (Vmax) without a change in carrier affinity (KD). Furthermore, the increase in transport capacity is too large to be attributed, in most cases, to simple intestinal hypertrophy. In the streptozotocin-treated chronically diabetic rat model, specific binding indicated an enhanced total number of glucose carriers in the small intestine compared with controls. Furthermore, autoradiography reveals that specific phlorizin (i.e., glucose) binding extends into the intervillous region of the intestine, while in age-matched controls binding is confined to the villous tip. These studies suggest that during experimental diabetes mellitus in rats, enhanced intestinal nutrient absorption may occur as a consequence of recruitment of carriers into previously nontransporting enterocytes. This review looks at ways in which this alteration may be influenced, and examines the expression of various isoforms of Na-K ATPase during streptozocin-induced diabetes mellitus.
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PMID:Adaptation of small intestinal membrane transport processes during diabetes mellitus in rats. 218 77

Endogenous factors cross-reacting with antidigoxin antibodies have been found in several tissues and body fluids of animals and humans, using commercially available digoxin radioimmunoassay or enzyme immunoassay methods. The chemical characteristics of these endogenous factors are, at present, unknown, although it has been suggested that they could be substances with low molecular weight. Experimental studies and theoretical considerations indicate that endogenous digitalis-like factors (DDLFs), in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, EDLF can be an endogenous modulator of the membrane sodium-potassium pump and several authors have suggested that EDLF could play a role in the regulation of fluids and electrolytes, muscular tone of myocardial and also in the pathogenesis of arterial hypertension. In this review, the authors discuss the hypothesis that, in metabolic diseases such as diabetes mellitus, obesity and acromegaly, the sodium retention and volume expansion, possibly due to exaggerated sodium intake, and/or exogenously induced peripheral hyperinsulinemia and high levels of growth hormone, could trigger a sustained release of EDLF, which in turn increases the blood pressure.
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PMID:Is the endogenous digitalis-like factor the link between hypertension and metabolic disorders as diabetes mellitus, obesity and acromegaly? 222 23

Nerve conduction slowing, a hallmark of both experimental and human diabetic neuropathy, is improved or corrected by aldose reductase inhibitors such as sorbinil. Recent animal experiments attribute acutely reversible nerve conduction slowing in diabetes to a myo-inositol (MI)-related defect in the nerve Na-K-ATPase (which generates the transmembrane sodium and potassium potentials necessary for nerve impulse conduction and the sodium gradient necessary for sodium-dependent uptake of substrates). This MI-related abnormality in Na-K-ATPase function is currently viewed as a cyclic, metabolic defect involving sequential alteration of Na-dependent MI uptake, MI content, MI incorporation into membrane phospholipids, and phospholipid-dependent Na-K-ATPase function in peripheral nerve. Aldose reductase inhibitors have been shown to normalize both nerve MI content and nerve Na-K-ATPase activity. These observations suggest that the acute effects of aldose reductase inhibitors on nerve conduction in both diabetic animals and patients may be mediated by correction of an underlying MI-related nerve Na-K-ATPase defect. Furthermore, this sorbinil-corrected Na-K-ATPase defect in diabetic nerve may contribute to other biochemical, functional, and structural abnormalities present in patients with diabetic peripheral neuropathy.
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PMID:A sodium-pump defect in diabetic peripheral nerve corrected by sorbinil administration: relationship to myo-inositol metabolism and nerve conduction slowing. 242 Nov 35

Time-dependent alterations in integrated cardiovascular function were assessed in the streptozotocin-diabetic rat. Hemodynamic measurements in the intact, anesthetized animal revealed significant and progressive reduction in heart rate after 2, 4, and 8 weeks of diabetes. Myocardial contractility (+ dP/dt) and rate of relaxation (-dP/dt) were preserved at 2 weeks, but progressively declined thereafter. Integrative mechanisms maintained mean arterial blood pressure within normal limits at all time points. Pressure was regulated by minimizing cardiac output reduction via slight increases in stroke volume (Starling mechanism) and concomitant small increases in total peripheral resistance. In response to graded isoproterenol infusion and brief, total aortic occlusion, percent increase of heart rate and + dP/dt was maintained despite decrements in absolute values. Reduced peripheral vasodilation resulted in elevated sensitivity of the heart rate-blood pressure relationship during isoproterenol challenge. The -dP/dt was uniformly impaired in diabetic rats during isoproterenol infusion. When given a rapid saline infusion, diabetic hearts appropriately augmented volume output via the Starling mechanism. Initial hemodynamic abnormalities observed in the intact, diabetic rat are consistent with known defects in cardiac adrenergic receptor density, contractile protein ATPase activity, and sarcoplasmic reticulum calcium uptake. However, many cellular and subcellular defects are compensated by integrative hemodynamic mechanisms while latent alterations are observed only in the intact cardiovascular system.
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PMID:Integrative nature and time course of cardiovascular alterations in the diabetic rat. 242 82


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