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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Na+-pumping activity of the erythrocyte plasma membrane in diabetic subjects was studied together with the lipid composition. Insulin-dependent diabetes mellitus (IDDM) patients (n = 25) were divided into young (28.1 +/- 7.4 yr old, mean +/- SD; n = 16) and old (7.17 +/- 9.8 yr old; n = 10) subjects; the age of non-insulin-dependent (NIDDM) patients was 70.7 +/- 11.5 yr (n = 10). The Na+-pumping activity, estimated from both Na+-K+-ATPase and ouabain binding, was significantly decreased in IDDM and NIDDM subjects, but its insulin sensitivity was retained only in young IDDM subjects. The total cholesterol and phospholipid content of the erythrocyte plasma membrane was lowered in IDDM subjects, and cholesterol-to-phospholipid molar ratio was significantly decreased. In NIDDM subjects the significant decreased of the two lipid components did not alter their ratio. The analysis of major phospholipid components of erythrocyte membranes revealed that only phosphatidylcholine is significantly increased in young diabetic subjects. The fatty acid composition of major phospholipid classes was significantly altered in all cases: the unsaturation index appeared to be increased in phosphatidylserine and sphingomyelin for both IDDM and NIDDM subjects and was also increased in phosphatidylcholine in the latter group.
Diabetes 1989 Jul
PMID:Membrane lipid alterations and Na+-pumping activity in erythrocytes from IDDM and NIDDM subjects. 254 70

Neuroblastoma cells were used to analyze the effect of galactose supplementation on myo-inositol metabolism, polyol accumulation, and Na+-K+ pump activity. Culturing cells in 30 mM galactose for a minimum of 1 wk led to a large accumulation of intracellular galactitol and a greater than 50% decrease in myo-inositol content. The effect of galactose on the intracellular content of galactitol and myo-inositol was concentration dependent. Extracellular myo-inositol accumulation and incorporation into phospholipid decreased by 20-30% in cells grown in 30 mM galactose. The decrease in myo-inositol accumulation is apparently due to a noncompetitive inhibition of high-affinity myo-inositol uptake. Treatment of the galactose-containing media with 0.4 mM sorbinil partially prevented the galactose-mediated decreases in myo-inositol metabolism and content. The galactitol content of the sorbinil-treated cells was significantly reduced compared with the galactitol levels in cells cultured in 30 mM galactose; however, galactitol levels remained significantly elevated over control cells. Exposing neuroblastoma cells to 30 mM galactose causes a decrease in the levels of phosphatidylinositol that is partially restored by the addition of sorbinil. The activity of the Na+-K+ pump was decreased by 20% in cells cultured in 30 mM galactose and was partially protected by sorbinil treatment. The effects of long-term galactose supplementation on myo-inositol metabolism, polyol accumulation, and Na+-K+-ATPase transport activity in cultured neuroblastoma cells are similar to the effects of high concentrations of glucose. These results provide additional evidence that the accumulation of polyol by neuroblastoma cells is partially responsible for alterations in myo-inositol metabolism and decreases in Na+-K+-ATPase transport activity.
Diabetes 1989 Aug
PMID:Effect of galactose and glucose levels and sorbinil treatment on myo-inositol metabolism and Na+-K+ pump activity in cultured neuroblastoma cells. 254 44

The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p less than 0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+-ATPase (3%) were all increased in the patients compared with the control children, being 2% (p less than 0.001), 2% (p less than 0.01), and 0.3% (p less than 0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.
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PMID:Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children. 254 82

The inotropic effects of isoproterenol (ISO), as well as the beta-adrenoceptors population, were measured in cardiac tissues from normal and short-term (3 days) diabetic rats. ISO increased the tension of both normal and diabetic ventricles, but the efficacy (Emax) of the concentration-response curve was greater on ventricles from diabetic rats than in those from the normal control. This phenomenon was accompanied by a decrease in the number of beta-adrenoceptor sites (Bmax) during diabetes. Insulin-treated diabetic hearts partially reversed the phenomenon. Propanolol blocked, in a competitive manner, the positive inotropic action of ISO in both types of ventricles. Inhibition of the synthesis and receptors of thromboxane (TX) reduced the hyperreactivity to ISO and increased the number of beta-adrenoceptors during diabetes, producing Bmax values almost similar to those of the normal heart. Additionally, the diabetic heart generated and released a greater amount of TXB2 than the normal heart, even in the presence or absence of ISO. The stimulatory effect of ISO upon TXB2 release was altered by the specific beta-adrenergic blockade and by verapamil. In addition, the drugs able to induce a sustained increase of endogenous cAMP also inhibited the release of TXB2 by diabetic ventricles. Exogenous TXB2 exerted the same type of hyperreactivity in diabetic ventricles. This phenomenon was accompanied by an inhibition of Na+ + K+-ATPase activity. These results suggest that beta-adrenergic inotropic stimulation is secondary to receptor-mediated hydrolysis of arachidonic acid with subsequent release of thromboxanes, which, in turn, may be responsible for both the superreactivity and the decrease in the number of beta-adrenoceptors during diabetes. The abnormal reactivity to beta-agonists also could be associated with alterations of the diabetic cardiac Na+ + K+-ATPase activity induced by TXB2 whose production is increased during diabetes.
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PMID:Role of thromboxanes in alterations of the diabetic beta-adrenergic system. 255 22

The binding capacity of ouabain to erythrocyte Na,K-ATPase was determined to analyze alterations in this enzyme activity in non-insulin-dependent diabetic patients. A significant (p less than 0.001) reduction of the binding capacity of ouabain was found in erythrocytes obtained from the diabetic patients with polyneuropathy (0.51 +/- 0.02 pmol/10(9) erythrocytes, m +/- SE, n = 14) as compared with the patients without neuropathy (0.67 +/- 0.02, n = 14) or age-matched control subjects (0.71 +/- 0.04, n = 11). Accordingly, the effect of an aldose reductase inhibitor (ARI; Ponalrestat) on erythrocyte Na,K-ATPase activity was studied following two or three months oral administration in seven of the diabetic patients with polyneuropathy. After treatment with Ponalrestat the mean binding capacity of ouabain was significantly increased from 0.53 +/- 0.04 to 0.57 +/- 0.03 (p less than 0.05 by paired t-test). Furthermore, enzyme kinetics showed that in normal subjects the apparent Km and Vmax of erythrocyte membrane Na,K-ATPase were 0.51 +/- 0.07 mM (n = 5, m +/- SE) and 7.19 +/- 0.27 nmol Pi/mg protein/min (n = 5, m +/- SE), respectively. The Vmax with 3 mM ATP was significantly (p less than 0.05) decreased in the diabetic patients with polyneuropathy as compared with age-matched control subjects. However, the apparent Km did not change. Finally, the in vitro effect of Ponalrestat was examined in erythrocyte membrane fractions from the diabetic patients with polyneuropathy. The activity of erythrocyte membrane Na,K-ATPase was found to be directly stimulated about 1.2 fold by the addition of pharmacological doses of Ponalrestat (10(-10), 10(-8), 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1989 Nov
PMID:Effect of aldose reductase inhibitor (Ponalrestat) on erythrocyte Na,K-ATPase activity in non-insulin-dependent diabetic patients with polyneuropathy. 256 96

A unifying metabolic hypothesis completely accounting for the development of one or more of the chronic complications of diabetes on the basis of a single aspect of disturbed glucose metabolism resulting from insulin deficiency and/or hyperglycemia has been sought by clinical and basic scientists for decades. A growing body of loosely related but internally consistent scientific data obtained from cultured cells, incubated tissue preparations, animal models, and man implicate sorbitol- and glucose-induced myo-inositol depletion and altered phosphoinositide metabolism in a series of secondary biochemical, functional, and architectural abnormalities in the PNS in diabetes. These early metabolically based functional and structural changes simulate those that characterize human diabetic neuropathy. Can abnormal phosphoinositide metabolism in diabetic nerve thereby by itself explain the development of chronic diabetic neuropathy with all of its clinical complexity and heterogeneity? Almost certainly not. Even if the entire contribution of hyperglycemia to the development of diabetic neuropathy were mediated by secondary abnormalities in phosphoinositide metabolism, other factors must also play a role. Witness the differences in the histopathological picture of neuropathy in patients with IDDM and NIDDM despite similar durations and severity of diabetes, the apparent influence of age and gender on the appearance of early neuropathy in patients with IDDM, and the association of alcohol consumption with diabetic neuropathy. While early metabolic and functional disturbances in diabetic nerve such as impaired (Na,K)-ATPase function and paranodal swelling are empirically attributable to abnormal myo-inositol and phosphoinositide metabolism, more advanced abnormalities such as axo-glial dysjunction may reflect superimposed independent biochemical and/or hormonal defects (although, as mentioned previously, aldose reductase inhibition decreases axo-glial dysjunction in diabetic humans). The PNS has only a limited repertoire of responses to a variety of insults, so that Wallerian degeneration, axonal atrophy, impaired axonal transport, and dystrophic changes in diabetic neuropathy may represent multiple factors. On the other hand, the increasingly recognized importance of the phosphoinositide cascade in neuromodulation may attribute a progressively wider range of disturbances in the diabetic PNS to myo-inositol depletion and associated defects in phosphoinositide metabolism. Thus, while all effects of aldose reductase inhibitors in the PNS of diabetic rats have been reproduced by myo-inositol supplementation when this alternative intervention has been tested, the exact role of phosphoinositide metabolism in most of these responses is not well understood.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of diabetic neuropathy: role of altered phosphoinositide metabolism. 256 4

There is a growing evidence for that in modern societies the function of the cellular sodium-potassium pump (membrane-bound Na+ K+ ATPase) in several tissues in man cannot respond adequately to demands. This is not seen in any other free-living vertebrates on this earth. The clearly unphysiological very high intake of sodium-chloride (salt) and also alcohol is definitely playing an important role in the development of the common degenerating metabolic aberrations, e.g. essential hypertension, diabetes II and severe over-weight, in man. The special and overall important role of the sodium-potassium pump for optimal cellular function and regeneration with special reference to the vascular tissues is presented and discussed.
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PMID:The sodium pump and energy regulation: some new aspects for essential hypertension, diabetes II and severe overweight. 258 82

In order to explore the pathogenetic mechanism underlying the changes in blood-brain barrier sodium transport in experimental diabetes, the effects of hyperglycemia and of hypoinsulinemia were studied in nondiabetic rats. In untreated diabetes, the neocortical blood-brain barrier permeability for sodium decreased by 20% (5.6 +/- 0.7 versus 7.0 +/- 0.8 X 10(5) ml/g/s) as compared to controls. Intravenous infusion of 50% glucose for 2 h was associated with a decrease in the blood-brain barrier permeability to sodium (5.4 +/- 1.2 X 10(5) ml/g/s), whereas rats treated with an inhibitor of insulin-secretion (SMS 201-995, a somatostatin-analogue) had normal sodium permeability (7.3 +/- 2.0 X 10(5) ml/g/s). Acute insulin treatment of diabetic rats normalized the sodium permeability within a few hours as compared to a separate control group (7.7 +/- 1.1 versus 6.9 +/- 1.4 X 10(5) ml/g/s). To elucidate whether the abnormal blood-brain barrier passage is caused by a metabolic effect of glucose or by the concomitant hyperosmolality, rats were made hyperosmolar by intravenous injection of 50% mannitol. Although not statistically significant, blood-brain barrier sodium permeability increased in hyperosmolar rats as compared to the control rats (8.3 +/- 1.0 and 7.0 +/- 1.9 X 10(5) ml/g/s, respectively). It is concluded that either hyperglycemia per se or a glucose metabolite is responsible for the blood-brain barrier abnormality which occurs in diabetes. Further, we suggest that the specific decrease of sodium permeability could be the result of glucose-mediated inhibition of the Na+K+-ATPase localized at the blood-brain barrier.
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PMID:Blood-brain barrier permeability to sodium. Modification by glucose or insulin? 264 96

To determine the effect of starvation on brain insulin receptors, rats were fed 4 g of chow/day for 14 days and then P2 fraction membranes were prepared from different brain regions. Compared to the fed state, there was an 18% reduction of insulin binding in olfactory bulbs from starved animals, but no change in the cerebellum, frontal cortex, amygdala, medial hypothalamus or lateral hypothalamus. A 15% reduction of olfactory bulb insulin binding was obtained by totally starving animals for four days. When membrane content was measured using the plasma membrane marker Na/K ATPase, insulin binding decreased by 26% and 14% in olfactory bulb membranes from starved and totally starved animals, respectively. The starvation-induced change in olfactory bulb binding was due to a loss of binding sites and not a decrease in binding affinity. Non-specific catabolism of protein and a change in the composition of membranes following starvation were excluded as causes for this effect. As streptozotocin induced diabetes had no effect on brain insulin binding, it was concluded that hypoinsulinaemia associated with starvation had not caused the reduction in olfactory bulb binding. Under similar conditions of starvation and diabetes, insulin binding in liver plasma membranes increased 26% and 38%, respectively. At 8 and 14 days of starvation, the reductions in olfactory bulb insulin binding and body weight were similar. On refeeding for three days, there was no increase in insulin binding, although body weight increased 7%. On refeeding for eight days, olfactory bulb insulin and body weight had returned to near normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of starvation on insulin receptors in rat brain. 274 26

Since the mechanisms responsible for stimulation of kidney Na-K-ATPase during streptozotocin-induced diabetes are unknown, we studied the possible role(s) of kidney hyperfiltration and hypertrophy and of hyperaldosteronism on Na-K-ATPase induction. For this purpose, we studied the relationship between Na-K-ATPase activity in individual nephron segments and alterations of glomerular filtration rate during the early phase of diabetes. Within 2 days after streptozotocin administration, Na-K-ATPase activity markedly increased in the proximal convoluted tubule, medullary thick ascending limb and cortical and outer medullary collecting tubule, but not in the proximal straight tubule, cortical thick ascending limb and distal convoluted tubule. Streptozotocin administration also markedly enhanced the glomerular filtration rate but only after 4 days following initiation of treatment. Changes in Na-K-ATPase were specific since the activity of adenylate cyclase, another marker of basolateral membranes, was not altered. Finally, when animals were adrenalectomized prior to streptozotocin treatment, Na-K-ATPase stimulation was curtailed in the collecting tubule but not in more proximal segments. These results suggest that diabetes alters Na-K-ATPase activity in specific nephron segments independent of alterations of glomerular filtration rate and of kidney hypertrophy, and that the stimulation of collecting tubule Na-K-ATPase is secondary to hyperaldosteronism.
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PMID:Mechanism of increased tubular Na-K-ATPase during streptozotocin-induced diabetes. 281 17


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