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)

Enzyme activities operative in glucose degradation and citrate cleavage pathway were studied in the adipose tissue of twenty-four patients with adult-onset diabetes and normal body weight, aged 59+/-9 years, and twenty-four matched controls. In normal tissue, type II (heat-inactivated) hexokinase moderately predominated over type I (heat-resistant). 6-Phosphofructokinase had an extremely low activity, which was by far the lowest among the ten glycolytic enzyme activities investigated, and which therefore might greatly limit the glycolytic rate. The level of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) was elevated above that occurring in other tissues. This, especially if considered together with the low 6-phosphofructokinase activity, would suggest a major role of pentose cycle in glucose degradation. Of the citrate cleavage pathway enzymes, ATP citrate-lyase, although having a lower activity than malate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), was readily measurable, which contrasts with previous data by others. This finding is consistent with the occurrence of lipogenetic capacity in human adipose tissue. In diabetic tissue, there was a decreased activity, both on a protein and on a wet-weight basis, of enzymes concerned with the glucose entry into metabolic pathways, namely hexokinase (both type I and, especially, type II) and pentose cycle dehydrogenases, as well as of pyruvate kinase. This could be connected with the defective glucose utilization by adipose tissue in diabetes. Beside the above-mentioned dehydrogenases, malate dehydrogenase (decarboxylating) (NADP) was also diminished. The reduction of these NADPH-forming enzymes, which supply reducing equivalents for fatty acid synthesis, would suggest a depressed lipogenesis.
Diabetes 1975 Oct
PMID:Enzymes of glucose metabolism and of the citrate cleavage pathway in adipose tissue of normal and diabetic subjects. 118 27

Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a broad range of aldehydes, including glucose. Since aldose reductase has been strongly implicated in the development of the chronic complications of diabetes mellitus, much effort has been devoted to understanding the structure and mechanism of this enzyme, and many aldose reductase inhibitors have been developed as potential drugs for the treatment of these complications. We describe here the 2.75 A crystal structure of recombinant human aldose reductase (Cys-298 to Ser mutant) complexed with NADPH. This mutant displays unusual kinetic behavior characterized by high Km/high Vmax substrate kinetics and reduced sensitivity to certain aldose reductase inhibitors. The crystal structure revealed that the enzyme is a beta/alpha-barrel with the coenzyme-binding domain located at the carboxyl-terminal end of the parallel strands of the barrel. The enzyme undergoes a large conformational change upon binding NADPH which involves the reorientation of loop 7 to a position which appears to lock the coenzyme into place. NADPH is bound to aldose reductase in an unusual manner, more similar to FAD- rather than NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in the crystal structure.
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PMID:The crystal structure of the aldose reductase.NADPH binary complex. 144 21

Aldose reductase (EC 1.1.1.21) is implicated in the pathophysiology of diabetic complications. In this paper we determined the activities of aldose reductase and ATPases of the erythrocytes in 17 patients with Type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). In the aldose reductase assay we used fluorometric method to avoid the disturbance of hemoglobin. With dihydronicotinamide adenine dinucleotide (NADH), we verified it was aldose reductase but not aldehyde reductase II that was activated in the erythrocytes of the patients with NIDDM. The aldose reductase activity of the erythrocytes in the patients was significantly higher (P less than 0.01) than that in the controls. The activity of Na+/K(+)-ATPase of the patients was significantly lower (P less than 0.01) than that of the controls. The activities of Ca(2+)-ATPase and Mg(2+)-ATPase on the erythrocyte membranes of the patients were similar to those of the controls. At the same time we measured the seven nucleotide concentrations in the erythrocytes of the patients. In this experiment we used ultrafiltration method, instead of acid precipitation to make it possible to determine dihydronicotinamide adenine dinucleotide phosphate (NADPH) and NADH. The concentrations of ATP, ADP and AMP were similar to those of the controls. The concentrations of NADPH, NAD+ and NADH in the erythrocytes of the patients were significantly lower (P less than 0.01, 0.05 and 0.05 respectively) than those of controls. The concentration of nicotinamide adenine dinucleotide phosphate (NADP+) in the patients was significantly higher (P less than 0.01) than that of controls.
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PMID:Activities of aldose reductase, ATPases, and nucleotide concentrations of erythrocytes in patients with type 2 (non-insulin-dependent) diabetes mellitus. 166 Dec 22

Aldose reductase is an NADPH-dependent enzyme which catalyzes the reduction of glucose to sorbitol. Specific potent inhibitors of aldose reductase are of potential pharmacological use because elevated levels of sorbitol produced by this enzyme in lens, peripheral nerve, retina, and renal glomeruli may be responsible for the pathogenesis associated with chronic diabetes. These inhibitors could also serve as probes of the mechanism of action of aldose reductase. anti-Oximes of aromatic aldehydes (e.g., benzaldoxime and 4-fluorobenzaldoxime) have proved to be effective inhibitors of aldose reductase rivaling pharmacological agents currently used to inhibit this enzyme in vivo. The kinetic patterns of inhibition in which benzyl alcohol is used as the oxidizable substrate suggest that the inhibition is due to the formation of a stable ternary complex composed of aldose reductase, NADP+, and the anti-oxime. Analogus ternary complexes are formed at the active site of horse liver alcohol dehydrogenase which is also inhibited by anti-oximes of efficient substrates.
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PMID:New inhibitors of aldose reductase: anti-oximes of aromatic aldehydes. 191 Feb 96

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).
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PMID:Changes in AMP deaminase activities in the hearts of diabetic rats. 202 37

The diabetic patient receiving nutritional support presents a particular challenge to critical care nurses and other members of the health care team. Typical protocols concerning TPN administration must be reevaluated given the special considerations associated with the pathology of diabetes mellitus. These patients are particularly susceptible to the development of acute complications including those associated with glucose metabolism abnormalities and electrolyte imbalances. In addition, diabetic patients receiving TPN have the added stress of an acute illness complicating a chronic illness. An understanding of the interrelationships between the pathophysiology of diabetes mellitus and the stress response will provide the nurse with the background information necessary to meet the challenges imposed by TPN administration. The critical care nurse will be able to recognize early signs and symptoms of complications and implement appropriate nursing interventions. An overview of primary nursing diagnoses, goals, and interventions has been presented and will apply to most patients receiving nutritional support. Individualized care plans can now be formulated as an extension of the basic plan, thus ensuring optimum nursing care to the diabetic patient receiving nutritional support.
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PMID:Nursing management of the diabetic patient receiving nutritional support. 211 56

The diabetic patient receiving TPN presents a challenge to health care personnel. Usual protocols concerning TPN administration must be reevaluated given the special considerations associated with the pathology of diabetes mellitus. These patients are susceptible to the development of complications including those associated with glucose metabolism abnormalities and electrolyte imbalances. In addition, diabetic patients receiving TPN have the added stress of an acute illness complicating a chronic illness. An understanding of the interrelationships between the pathophysiology of diabetes mellitus and the stress response will provide the nutritional support team with the background information necessary to meet the challenges imposed by TPN administration. The health care team will be able to recognize early signs and symptoms of complications and implement appropriate interventions. Individualized care plans can be formulated as an extension of the basic plan that has been presented, thus providing optimum care to the diabetic patient receiving nutritional support.
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PMID:Management of the diabetic patient receiving nutritional support. 250 78

Diet therapy is an important factor in overall care of most GI patients. Historically, diets have been used unscientifically in many of these patients without positive results. Nutritional care and diet therapy are critical for two reasons. First, malnutrition is an expected sequelae to most, if not all, GI diseases or disorders. Failure to eat, digest, or assimilate nutrients can provoke malnutrition in just a few weeks, although careful assessment of anthropometric, clinical, biochemical, and nutritional history by a trained professional can protect against this. Diet therapy through the elimination of offending foods such as wheat gluten or lactose, or inclusion of specialized products such as medium chain triglycerides or elemental formulas, can sustain nutritional status. Dietary components such as insoluble fiber appear to have physiologic effects, while soluble fibers may have metabolic effects important to diabetes and cardiovascular disease. There is a high potential for malnutrition in Crohn's disease during active and remittent phases. Elemental enteral formulas or TPN are used during the active phase to ensure optimal nutritional status and bowel rest. Hyperalimentation using the GI tract during remittent stage maintains this. Avoiding offending foods by Crohn's patients is an acceptable practice as long as entire categories of foods are not deleted. Avoiding all foods containing gluten from wheat, rye, barley, and oats, however, is a crucial prerequisite to recovery from celiac disease. Gluten is commonly used as a stabilizer, emulsifier, and extender in the food industry and is not always shown on food labels. Careful consultation with a registered dietitian can identify hidden sources of gluten in the diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary therapy in gastrointestinal disease. 264 90

Gastrointestinal disorders associated with diabetes mellitus have a prevalence rate of 30 to 75%. The most prominent disorders are gastroparesis, diarrhea, and constipation. Severity of symptoms range from mild to severe with the most affected patients being at risk for the development of protein calorie malnutrition. An historical review of the major studies which defined the diagnosis, pathophysiology, and prevalence of these disorders is presented. Guidelines for accurate nutritional assessment, which is essential to the decision to initiate nutritional therapy in this difficult to assess population, are also included. Current methods devised for treatment of diabetic gastroparesis and related disorders are presented. Emphasis is placed on recent developments in nutritional support techniques which make it possible to meet the energy requirements of all such patients. Practical outlines for glucose control in patients receiving TPN or enteral feeding and guidelines for transitioning from parenteral feeding to an oral diet are also presented.
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PMID:Overview of gastrointestinal disorders due to diabetes mellitus: emphasis on nutritional support. 264 46

Transglutaminase activity in rat islet homogenates was increased after preincubation of the islets at high glucose concentration, and severely decreased after preincubation in the presence of either 1,2-bis(2-chloroethyl)-1-nitrosurea or 2-cyclohexene-1-one. The stimulatory action of glucose was still observed when the islets were preincubated in the absence or extracellular Ca2+. The enzymic activity was decreased by NAD+ or NADP+ but not NADH or NADPH, and inhibited by GSSG more than by GSH. These findings suggest that the glucose-induced activation of transglutaminase may be related to induction of a more reduced redox state with subsequent change in thiol-disulfide balance.
Diabetes Res 1986 Mar
PMID:Glucose-induced activation of transglutaminase in pancreatic islets. 287 59


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