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 permeabilities of the blood-retinal (BRB) and blood-brain (BBB) barriers to sucrose were determined simultaneously using an intravenous injection technique in the rat. The method involved direct sampling of retinal tissue in order to avoid errors caused by sucrose penetration across other components of the blood-ocular barrier. The permeability X surface area (PS) product for the BRB was approximately four times greater than for the BBB. Intracarotid infusion of a hypertonic arabinose solution resulted in a dose-dependent increase in the permeability of both barrier systems. In contrast, 24 hr after treatment of animals with iodate, the PS product for the BRB but not the BBB was increased. The permeability of the blood-retinal barrier to sucrose was measured in normal and 2-, 6-, and 20-week streptozocin diabetic rats. The BRB was unaffected at 2 and 6 weeks of diabetes, and showed only a small increase in permeability at 20 weeks. Our results suggest that alterations in the blood-ocular barrier in early diabetes do not result from an increased passive permeability of the BRB. The method described should permit direct comparison of BRB and BBB permeabilities to a variety of compounds under various conditions.
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PMID:Sucrose permeability of the blood-retinal and blood-brain barriers. Effects of diabetes, hypertonicity, and iodate. 372 87

To determine whether an agent such as WY-41,747, a long-acting somatostatin analogue, could be useful as an adjunct to insulin in the treatment of diabetes mellitus, postprandial plasma glucose concentrations were determined in subjects with insulin-dependent diabetes rendered euglycemic with the Biostator insulin infusion device under four conditions: (1) subcutaneous minipump infusion of insulin alone (13 +/- 1 units) over 30 minutes beginning 30 minutes before ingestion of a meal using insulin doses determined by the Biostator; (2) the same conditions as 1 but beginning immediately before meal ingestion; (3) the same conditions as 1 but with less insulin (7 +/- 1 units) accompanied by the analogue (0.01-0.05 mg/kg); (4) the same conditions as 2 but with the analogue and less insulin (11 +/- 1 units). Administration of the somatostatin analogue increased the effectiveness of insulin in controlling postprandial hyperglycemia and permitted satisfactory postprandial glycemic control when the insulin infusion was initiated immediately before meal ingestion. Administration of the analogue suppressed postprandial plasma glucagon and triglyceride concentrations and delayed xylose absorption. These results suggest that subcutaneous administration of a long-acting somatostatin analogue such as WY-41,747 along with insulin may be clinically useful in the treatment of diabetes mellitus.
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PMID:Effects of a long-acting somatostatin analogue on postprandial hyperglycemia in insulin-dependent diabetes mellitus. 613 93

The effects of a zinc phosphate suspension of a long-acting, reportedly selective somatostatin analog, Des-Ala1,Gly2 [His4,5,D-Try]-somatostatin (100 micrograms/kg) on postprandial plasma glucose, glucagon, xylose and triglyceride levels were evaluated in alloxan diabetic dogs. Compared to the analog in aqueous solution, the zinc phosphate suspension had a more gradual onset of action in suppressing plasma glucose and xylose levels but a similar onset of action on suppression of plasma triglyceride and glucagon responses. On all these responses, the zinc suspension had a duration of action (greater than 6 hrs) at least three times as long as the aqueous solution. We conclude that such a somatostatin analog in zinc phosphate suspension may have a sufficient duration of action to be useful as an adjunct to insulin in the treatment of diabetes mellitus.
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PMID:Effect of a zinc phosphate suspension of a long-acting somatostatin analog on postprandial plasma glucose, triglyceride and glucagon concentrations in alloxan diabetic dogs. 615 Nov 11

An unusual case of Yersinia pseudotuberculosis septicemia is reported. Diabetes mellitus was the sole underlying disease; liver enzyme elevations were only transitory. The strain did not show motility until after 50 days at room temperature; it showed temperature and media-dependent fermentation of arabinose, melibiose and rhamnose.
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PMID:Yersinia pseudotuberculosis: unusual features of a case. 635 10

The effect of adebit (N-butylbiguanide) on the rat tissues in vitro, namely, on sugar consumption and transport, glucose oxidation, as well as on gluconeogenesis in the rat organism, was studied. Glucose consumption and D-xylose transport in the diaphragms of intact animals and glucose consumption and oxidation in the epididymal fat of rats, given hydrocortisone, were determined. Gluconeogenesis intensity under adebit action was investigated according to the blood sugar level following adrenaline injections to rats after 24-hour fasting. It was established that the administration of adebit at concentrations of 0.2 to 0.5 mM results in intensified insulin-independent glucose consumption and xylose transport in the diaphragm, the maximum transport rate being augmented and the dissociation constant remaining unchanged. It is concluded that adebit does not change the properties of sugar transmitter, but influences the cell metabolism by inhibiting oxidative phosphorylation. The use of adebit in therapeutic concentrations (5 to 10 mcM) gave an insulin-dependent rise of glucose consumption and oxidation in the fatty tissue by 44%. A decrease in the blood sugar level in the presence of adrenaline hyperglycemia under the action of adebit therapeutic doses was not observed. It is concluded that biguanide hypoglycemizing action in diabetes mellitus is based on the biguanide potentiated insulin effectiveness.
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PMID:[Effect of adebit (N-butylbiguanide) on the metabolism and oxidation of glucose in rat tissues in vitro]. 651 86

The ionophore A23187 (10 micrograms/ml) did not affect the uptake of D-[U-14C]xylose by rat soleus muscle incubated under basal conditions. When muscles were incubated in a Ca2+/Mg2+-free (CMF) medium, A23187 promoted the efflux of intracellular Mg2+ and the efflux of 45Ca from preloaded muscles. Under these conditions, conditions, A23187 inhibited insulin-stimulated sugar transport without affecting 125I-insulin binding by the muscle. A23187 induced a slight fall in muscle ATP (16-18%); this does not appear to be responsible for the inhibitory effect of the ionophore on sugar transport. The inhibitory effect of A23187 was completely abolished when the CMF medium was supplemented with Mg2+ and partially reversed by Mn2+ or Zn2+; supplementation with Ca2+ did not reverse the inhibitory effect of the ionophore. These results suggest that insulin stimulates muscle sugar transport through a mechanism that involves intracellular Mg2+.
Diabetes 1982 Oct
PMID:Effect of ionophore A23187 on basal and insulin-stimulated sugar transport by rat soleus muscle. 681 67

Arylsulfonylamino acids, displaying a wide range of inhibitory activities versus rat lens aldose reductase (RLAR), were analyzed for enzyme selectivity in several test systems. These RLAR inhibitors were found not to produce significant inhibition of genetically-linked reductases (aldehyde reductase, ALR), catalytically similar reductases (Pachysolen tannophilus xylose reductase, PTXR), functionally distinct oxidoreductases (glutathione reductase, GR, lactate dehydrogenase, LDH, and gamma-transaminase, GABA-T), and thymidylate synthase (TS). These data suggest that aldose reductase differs significantly from other oxidoreductases in its inhibitor binding domain(s). Furthermore, the aldose reductase selectivity demonstrated by the arylsulfonylamino acids suggests that these compounds may not inhibit other key metabolic transformations in various cell types and that they may function as selective probes for studies of the relationship between aldose reductase mediated biochemical changes and the pathologies of chronic diabetes.
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PMID:Enzyme selectivity analyses of arylsulfonylamino acid aldose reductase inhibitors. 750 72

Using 31P-nuclear magnetic resonance spectroscopy, we have identified elevated concentrations of sedoheptulose-7-phosphate (S-7-P) in lenses from three animal models of hyperglycemia: streptozotocin-induced diabetic rats, galactose-fed rats, and xylose-fed rats. This observation provides a unique and independent confirmation of the activation of the hexose monophosphate shunt (HMPS) pathway in the hyperglycemic lens in vivo. While the elevation in concentration of S-7-P was very dramatic, the other HMPS metabolites in these tissues were below the threshold of detection, as expected for the HMPS pathway near equilibrium. In terms of nonenzymatic glycation, these results suggest that the only HMPS metabolite of importance in the hyperglycemic rat lens is S-7-P. Although in the diabetic lens its role appears to be relatively minor, in the galactosemic lens this compound may be an important contributor to the increased production of advanced glycosylation end products.
Diabetes 1995 Jul
PMID:31P-nuclear magnetic resonance evidence of an activated hexose-monophosphate shunt in hyperglycemic rat lenses in vivo. 778 49

Glycation and oxidation reactions contribute to protein modification in aging and diabetes. Formation of dicarbonyl sugars during autoxidation of glucose is the hypothetical first step in the autoxidative glycosylation and subsequent browning of proteins by glucose [Wolff, S. P., & Dean, R. T. (1987) Biochem. J. 245, 243-250]. In order to identify the dicarbonyl sugar(s) formed during autoxidation of glucose under physiological conditions, glucose was incubated in phosphate buffer (pH 7.4) at 37 degrees C under air (oxidative conditions) or nitrogen with transition metal chelators (antioxidative conditions). Dicarbonyl compounds were analyzed spectrophotometrically and by HPLC after reaction with Girard-T reagent. Carbohydrates were analyzed by gas chromatography-mass spectrometry. Both dicarbonyl sugar and arabinose concentrations increased with time and glucose concentration in incubations conducted under oxidative conditions; only trace amounts of these products were detected in glucose incubated under antioxidative conditions. HPLC analysis of adducts formed with Girard-T reagent indicated that glyoxal was the only alpha-dicarbonyl sugar formed on autoxidation of glucose. Glyoxal and arabinose accounted for > or = 50% of the glucose lost during a 21 day incubation. Neither glucosone nor its degradation product, ribulose, was detectable. Reaction of glyoxal with RNase yielded the glycoxidation product, N epsilon-(carboxymethyl)lysine, while arabinose is a source of pentosidine. Our results implicate glyoxal and arabinose as intermediates in the browning and crosslinking of proteins by glucose under oxidative conditions. They also provide a mechanism by which antioxidants and dicarbonyl trapping reagents, such as aminoguanidine, limit glycoxidation reactions and support further evaluation of these types of compounds for inhibition of chemical modification and crosslinking of proteins during aging and diabetes.
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PMID:Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. 789 66

Mounting experimental evidence links increased aldose reductase activity with diabetes-related kidney functional changes. To investigate the interrelationship of NADPH-dependent reductases in the human kidney, both aldose reductase and aldehyde reductase were purified from human kidney by a series of chromatographic procedures, including gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A, and chromatofocusing on Mono P. Each purified enzyme appeared as a single band on polyacrylamide gel after electrophoresis or isoelectric focusing. Aldose reductase has a pI of 5.7 and apparent molecular weight of 37 kDa, calculated from SDS-polyacrylamide gel electrophoresis, while aldehyde reductase has a pI of 5.2 and molecular weight of 39 kDa. Similar molecular weights were also obtained by gel filtration, indicating that both aldose and aldehyde reductases are present as monomers in the human kidney. Aldehyde reductase is primarily localized in the cortex, while the medulla contains aldose reductase. Both enzymes displayed properties consistent with the general characteristics of aldose and aldehyde reductases obtained from either rat or dog kidney. Purified aldose reductase utilizes aldose sugars such as D-xylose, D-glucose, and D-galactose as substrates while aldehyde reductase preferentially reduces D-glucuronate and oxidizes L-gulonate to D-glucuronate. Despite the lower apparent affinity of aldehyde reductase for aldose sugars (approximately 20- to 100-fold less) both enzymes reduced D-xylose, D-glucose, and D-galactose to their respective sugar alcohols in in vitro incubation studies where the generated sugar alcohols were identified by gas chromatography. Both enzymes were also inhibited by aldose reductase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
J Diabetes Complications
PMID:Human kidney aldose and aldehyde reductases. 834 12


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