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)

Diarrhea is a common symptom in long-standing diabetes. The pathogenesis of this diarrhea remains obscure, although it appears to be related to the development of autonomic neuropathy, which may cause several abnormalities including altered gut motility. We studied fasting gastrointestinal motility for a mean of 210 min in a group of 12 type-II diabetics with diarrhea. All patients had peripheral neuropathy and symptoms of autonomic neuropathy. Their motor activity was compared with that of a group of six normal volunteers. In addition, gastrointestinal transit time was assessed by the hydrogen breath test. The presence of bacterial overgrowth was assessed by the hydrogen breath test and culture of jejunal secretions. The diabetics showed grossly disordered motor activity. There was a complete absence of phase-III activity in two patients. Most phase III's commenced in the distal duodenum or jejunum. The phase-III component was often of short duration at each recording site. There was increased velocity of propagation between sites. Continuous phase-II activity was noted in some patients. Antral activity was absent or reduced during phase II. Gastrointestinal transit time was significantly prolonged in the diabetics. Bacterial overgrowth was demonstrated in three diabetic subjects. These motility abnormalities are nonspecific and are unlikely to play a major role in the pathogenesis of diabetic diarrhea.
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PMID:Abnormalities of the migrating motor complex in diabetics with autonomic neuropathy and diarrhea. 336 94

Methods for designing, fabricating, testing in vitro and in vivo, and improving chronically implantable oxidase/peroxide-type polarographic glucose sensors are described. Voltammetric means to evaluate oxygen supply to the sensor and to measure the nearby microcirculation with hydrogen washout techniques using the implanted glucose sensor are outlined. Because some peritoneally implanted sensors have, perhaps surprisingly, remained functional for months, such devices may prove with further development to be useful as the sensing components in artificial pancreatic beta cells for the control of diabetes.
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PMID:Long-term implantation of voltammetric oxidase/peroxide glucose sensors in the rat peritoneum. 337 63

We evaluated the possibility that impaired insulin-receptor kinase activity contributes to insulin resistance by examining in vitro receptor tyrosine kinase activity and in situ receptor phosphorylation in four models of insulin resistance. Adipocytes from streptozocin-induced nonketotic diabetic (STZ-D), glucocorticoid-treated, fasted, and chronically uremic rats showed reduced basal and maximally insulin-stimulated 2-deoxy-D-glucose transport compared with matched controls. Adipocytes from these models were also resistant to stimulation of hexose transport by hydrogen peroxide, a postbinding insulin mimicker. Changes in the number of insulin receptors per cell could not account for these alterations in transport. Cell surface 125I-labeled insulin binding was 142% of control in STZ-D and 129% with fasting and unchanged in glucocorticoid excess and chronic uremia. Insulin-stimulated tyrosine kinase was measured by means of a synthetic substrate, Glu80Tyr20. Partially purified receptors from these resistant models had unaltered kinase activity when normalized to soluble 125I-insulin binding. In situ stimulation of receptor phosphorylation by 7 and 100 nM insulin was determined after equilibration of adipocytes with 32PO4. Compared with matched controls, these intact cells, from all four resistant models, had insulin-stimulated receptor phosphorylation that was unchanged per unit of cell surface binding. Similar to results with insulin, hydrogen peroxide stimulation of in situ receptor phosphorylation was unchanged in each model. Thus, both in vitro and in situ measures of receptor phosphorylation suggest that the cellular alterations leading to insulin resistance in these adipocytes resides beyond phosphorylation of the insulin receptor.
Diabetes 1988 Feb
PMID:Intact adipocyte insulin-receptor phosphorylation and in vitro tyrosine kinase activity in animal models of insulin resistance. 339 39

Plasma renin activity, plasma aldosterone levels and renal tubular capacity to excrete hydrogen ions were studied in 13 patients suffering from diabetes mellitus with a creatinine clearance of less than 40 ml/min. The results were compared with those obtained in a control group, in a group of nondiabetic subjects with chronic renal failure (CRF) and in a group of diabetic patients without CRF. Twelve of the thirteen diabetic patients with CRF had data characteristic of hyporeninemic hypoaldosteronism associated with type IV renal tubular acidosis. On comparing the results with those of the other two groups of patients, it was observed that the manifestations of the latter two groups considered separately were different from those of the problem group, although in the diabetic patients with normal glomerular filtration rate (GFR) hyporeninism but not hypoaldosteronism was present accompanied by a lower net acid excretion (p less than 0.001) due to a lower excretion of NH4 (p less than 0.05) and titratable acid (p less than 0.001) when the patients were challenged with an NH4Cl overload. We believe that a conjunction of diabetes and renal failure is necessary for the diabetic patients with a decrease in GFR to show hyporeninemic hypoaldosteronism and type IV tubular acidosis.
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PMID:Hyporeninemic hypoaldosteronism in diabetic patients with chronic renal failure. 339 21

The condition of diabetes mellitus is described with particular reference to the parameters that it would be desirable to monitor in order to improve management and understanding of the disease. Previous attention has largely focused on analysis of glucose, but many other intermediates of carbohydrate, fat and protein metabolism are deranged in diabetes and may be alternative measures of control. The need for laboratory analysers, self-monitoring, closed-loop devices and alarms are detailed and the problems associated with implantable sensors discussed. Progress in the development of biosensors is reviewed using glucose sensors as the main example. Electrochemical, optoelectronic and calorimetric approaches to sensing are considered and it is concluded that configurations based either on hydrogen peroxide detection or on mediated electron transfer are most likely to provide a raid route to in vivo monitoring. The extension of biosensor technology to tackle other important substrates is discussed, the principal hurdle to success being seen as the lack of long-term stability of the biological component.
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PMID:Diabetes mellitus: biosensors for research and management. 391 72

Chemiluminescence induced in isolated islets from rat pancreas by the diabetogenic drugs, alloxan and streptozotocin, has been measured. The assay system consisted of 3 microM of luminol, 10 islets, and 100 microM of alloxan or 500 microM of streptozotocin in 5 ml Krebs-Ringer bicarbonate buffer containing 16 mM of Hepes (pH 7.4). Alloxan-induced chemiluminescence appeared very rapidly and lasted more than 5 min. On the other hand, streptozotocin failed to produce chemiluminescence over a period of 60 min after addition. The presence of superoxide dismutase (1000 U/ml) and/or catalase (100 U/ml) markedly suppressed alloxan-induced chemiluminescence. These results suggest that alloxan acts as an exogenous free radical generator in pancreatic islets, but that streptozotocin does not. The involvement of superoxide anion and hydrogen peroxide in production of chemiluminescence by alloxan suggests that the hydroxyl radical may mediate this chemiluminescence.
Diabetes 1984 Feb
PMID:Chemiluminescence as an index of drug-induced free radical production in pancreatic islets. 622 39

Acarbose, an alpha-glucosidase inhibitor, lowers the glycemic excursion following the ingestion of carbohydrates, in particular, sucrose. This was confirmed with increasing doses of acarbose (0, 50, and 100 mg) and the causes investigated. The absorption of the glucose moiety of sucrose was determined from plasma tracer concentrations when overnight-fasted normal subjects received a 100-g oral sucrose load labeled with sucrose [(1-14C]glucose and a simultaneous intravenous infusion of [3-3H]glucose. As the dose of acarbose given with the sucrose load was increased from 0 to 100 mg, the percentage of the load appearing in the peripheral circulation decreased from 90% to 62%. Malabsorption was confirmed by the appearance of breath hydrogen. Simultaneously, absorption time increased from 243 to 411 min. Maximal glycemic excursions were therefore lowered from 64 to 31 mg/dl. The plasma concentrations of gastric inhibitory polypeptide and insulin decreased with the acarbose dose so that the fractional disappearance rate of glucose also decreased. However, the concentrations of glucagon-like immunoreactivity (GLI) rose, confirming the ileal appearance of malabsorbed sucrose.
Diabetes 1984 Mar
PMID:The effects of an alpha-glucoside hydrolase inhibitor on glycemia and the absorption of sucrose in man determined using a tracer method. 636 57

The effect of insulin on glucose transport (2-deoxyglucose uptake) in adipocytes was measured in the absence and in the presence of 10 mM sodium-DL-beta-hydroxybutyrate. The ketone body had little or no effect on the basal or the maximally insulin-stimulated rate of transport. However, beta-hydroxybutyrate potentiated the effect of submaximal concentrations of insulin, i.e., it resulted in a leftward shift in the dose-response curve. The half-maximally effective concentration of insulin was decreased by approximately 30% from 0.58 ng/ml to 0.40 ng/ml. beta-Hydroxybutyrate caused a slight (approximately 10%) increase in 125I-insulin binding to the cells. To determine whether this small increase in insulin binding is responsible for the increased insulin sensitivity in the presence of the ketone, two mimickers of insulin action were used: a serum containing anti-insulin receptor antibodies and hydrogen peroxide. beta-Hydroxybutyrate increased the sensitivity of glucose transport to stimulation by the anti-receptor antibody, demonstrating that insulin itself does not have to be present. beta-Hydroxybutyrate also potentiated the effect of hydrogen peroxide (which acts at a level distal to the insulin receptor) even in cells that had been depleted of insulin receptors by trypsin treatment. Therefore, beta-hydroxybutyrate acts, at least partly, at a post-insulin receptor level. Adenosine increases the insulin sensitivity of adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Nov
PMID:beta-Hydroxybutyrate increases the insulin sensitivity of adipocyte glucose transport at a postreceptor level. 638 23

Pieces of rat epididymal fat tissue were maintained in a biochemically defined medium for 20 to 44 hours in either the absence or presence of a sulfonylurea at levels known to be effective in humans. Prolonged exposure of adipocytes to sulfonylureas did not influence the number of insulin receptors or their affinity to insulin or the ability of insulin to induce receptor loss (down-regulation). Also, the sulfonylureas did not influence the basal uptake of the D-glucose analogs 2-deoxyglucose and 3-O-methylglucose. However, exposure to these drugs resulted in a potentiation of the stimulatory effects of insulin on hexose transport at submaximal and maximally effective concentrations of insulin. The average potentiation was approximately 30%. In addition, sulfonylureas enhanced stimulation of hexose uptake by the insulin mimickers, hydrogen peroxide and vitamin K5. These oxidants are known to manifest insulin-like actions subsequent to insulin binding. Under conditions in which glucose transport was rate limiting, the conversion of glucose to carbon dioxide and the total lipids mirrored the findings of hexose uptake. However, at a glucose concentration of 50 mM, at which hexose transport is no longer rate limiting, sulfonylureas did not potentiate metabolism in th absence or presence of insulin. These results may help to explain the hypoglycemic action of the drug in view of the recent finding that a postreceptor deficit is present in noninsulin-dependent diabetes mellitus.
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PMID:Extrapancreatic effects of sulfonylureas. Potentiation of insulin action through post-binding mechanisms. 640 22

The diagnosis of ketoacidosis with an inordinately high plasma and urinary concentration ratio of beta-hydroxybutyrate (beta-OHB) to acetoacetate (AcAc) is difficult, because only AcAc and acetone react with the diagnostic reagents used clinically to detect ketones. The purpose of this study was to assess the validity of the claim that beta-OHB can be identified with a simple modification of the usual bedside test for ketones, using hydrogen peroxide (H2O2) and Ketostix (Ames Division, Miles Laboratories, Inc., Elkhart, Indiana). Unfortunately, the lowest detectable concentration of urinary beta-OHB was 50 mmol/L, and serum beta-OHB could not be detected at levels less than 100 mmol/L, a clinically irrelevant level. The relative insensitivity, the inapplicability to serum, and the potential hazard of the routine use of 30% H2O2 by practicing physicians or houseofficers render the method of limited value.
Diabetes Care
PMID:Can beta-hydroxybutyrate be detected at the bedside by in vitro oxidation with hydrogen peroxide. 642 53


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