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)

To assess the effects of streptozotocin-induced diabetes on the substrates utilized in the formation of glycoproteins, the pools of uridine 5'-diphosphoglucose (UDPG), uridine 5'-diphosphogalactose (UDP-GAL), uridine 5'-diphosphoglucuronic acid (UDPGA), and uridine 5'-diphospho N-acetyl galactosamine (UDPA-GAL) were measured in the renal cortex of control and over a 48-hr period in diabetic rats. In control rats these pools measured: UDPG, 256 +/- 23; UDP-GAL, 75 +/- 14; UDPGA, 147 +/- 16; UDPAG, 367 +/- 23; UDPG-GAL, 131 +/- 13 nmoles/mg DNA. In diabetic rats, except for UDP-GAL, all pools were increased 41 to 68%. The incorporation of radiolabeled orotate was increased in all pools, except UDP-GAL, in diabetic rats by 41 to 77% compared to control rats. The incorporation into UDPG and UDPAG was increased even after correction for the specific radioactivity of their immediate precursor, uridine 5'-triphosphate (UTP). Expansion of the UTP pool after orotate infusion was associated with an increase in the size of the UDPG and UDPAG pools in both control and diabetic rats. Depletion of the UTP pool after adenine infusion in controls was associated with a decrease in all pools. This study demonstrates that after the induction of diabetes there is a rapid increase in the bioavailability of substrates utilized in the synthesis of glycoproteins and glycosaminoglycans. It is theorized that this increase is necessary for the augmented synthesis of basement membrane-like material in the diabetic kidney.
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PMID:Effects of early diabetes on uridine diphosphosugar synthesis in the rat renal cortex. 710 58

Diabetes mellitus is a disease that affects multiple organ systems. In our laboratory it has been shown that there is a significant loss of outer hair cells in genetically diabetic rats. Galactosemia can also produce diabetic-like changes. This study was performed to demonstrate whether these changes also occur in the cochlea. Three groups of Sprague-Dawley rats were used and fed either a control diet, a 50% galactose diet, or a 50% galactose diet with the addition of an aldose reductase inhibitor. After 6 months the animals were killed, and the cochleas were removed, fixed, and stained. Diabetes-induced damage was assessed by counting the hair cells and calculating the neuroganglion cell density. The histopathologic changes induced by galactose were manifested as outer hair cell loss and a decrease in neuroganglion cell density. Control animals had the least amount of hair cell loss and the greatest neuroganglion cell density of all three groups. Galactose-only animals demonstrated the most pronounced changes in both hair cell loss and neuroganglion cell degeneration; however, only changes of neuroganglion cell density in the basal turn were significant. The addition of an aldose reductase inhibitor provided inconclusive results in both hair cell determination and neuroganglion cell density; however, generally the inhibitor partially prevented the damage produced by galactose. These results suggest that a high-galactose diet can induce diabetic-like changes in the cochlea.
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PMID:Consumption of a high-galactose diet induces diabetic-like changes in the inner ear. 750 87

Galactose-fed rats develop a retinal microvascular disease, but retinopathy has not been found to develop reproducibly in diabetic rats. We sought to determine which retinal lesions can be reproducibly produced by long-term diabetes in rats, the extent to which the capillary lesions in diabetic rats and galactosemic rats are similar, and whether the retinopathy induced by 50% galactose can be reproduced satisfactorily by a lower concentration of galactose. Alloxan-diabetic rats and rats fed either a 50% galactose diet or a 30% galactose diet were killed after comparable durations of study (18 to 22 months). Rats fed 50% galactose showed greater than normal frequency of retinal pericyte ghosts and acellular capillaries, and thickening of capillary basement membranes by 18 months of galactosemia. Rats eating 30% galactose developed similar retinal lesions, and tended to be healthier than rats fed 50% galactose. Diabetes of 1 1/4 years or more likewise resulted in retinal pericyte ghosts, acellular capillaries and thickened capillary basement membrane. IRMAs and other vascular abnormalities were not reproducibly demonstrated at this duration of study, and saccular microaneurysms were not seen in any groups. In a number of diabetic rats, the severity of diabetes diminished spontaneously (after 1 to 1 1/2 years of insulin deficiency), thus making it essential that glycemia be systematically monitored. Both diabetic rats and experimentally galactosemic rats develop microvascular lesions that are consistent with at least the early stages of diabetic retinopathy, and these models should be useful to screen potential therapies for their ability to inhibit the development of retinopathy.
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PMID:Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats. 772 Mar 92

Galactose usually is ingested as lactose, which is composed of equimolar amounts of glucose and galactose. The contribution of galactose to the increase in glucose and insulin levels following ingestion of equimolar amounts of galactose and glucose, or lactose, has not been reported in people with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, we studied the effects of galactose ingestion alone, as well as with glucose either independently or in the form of lactose, in subjects with untreated NIDDM. Eight male subjects with untreated NIDDM ingested 25 g glucose, 25 g galactose with or without 25 g glucose, or 50 g lactose as a breakfast meal in random sequence. They also received 50 g glucose on two occasions as a reference. Water only was given as a control meal. Plasma galactose, glucose, glucagon, alpha-amino nitrogen (AAN), nonesterified fatty acids (NEFA), and serum insulin and C-peptide concentrations were determined over a 5-hour period. The integrated area responses were quantified over the 5-hour period using the water control as a baseline. Following ingestion of 25 g galactose, the maximal increase in plasma galactose concentration was 1 mmol/L. The mean maximal increases in plasma galactose concentration following ingestion of 25 g galactose + 25 g glucose or following 50-g lactose meals were similar and were only 12% of that following ingestion of galactose alone (P < .05). The mean galactose area response over the water control for the 25-g galactose meal was 0.95 +/- 0.31 mmol.h/L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glucose, galactose, and lactose ingestion on the plasma glucose and insulin response in persons with non-insulin-dependent diabetes mellitus. 824 70

Intact lenses from New Zealand white rabbits were incubated in tissue culture media containing either 5 mM glucose or 5 mM glucose plus 30 mM galactose. The standard media did not contain taurine. Lenses were also cultured in a third medium containing 30 mM galactose plus 0.2 mM taurine. The frequency of cataract formation was evaluated as a function of the culture media. One lens (1/10), in media containing 5 mM glucose, developed a lenticular opacification during a 72-h incubation. Lenses (12/15) incubated in 30 mM galactose, without taurine, developed cataracts; fewer lenses (2/13) exposed to 30 mM galactose plus 0.2 mM taurine developed cataracts (p < 0.005). Galactose cataracts have been associated with lens edema attributed to the osmotic stress of tissue polyol (galactitol) accumulation. The water content of the noncataractous and cataractous lenses in this experiment did not differ. Lens edema, therefore, was not thought to be important in cataract pathogenesis. Taurine, an organic osmolyte was lower (5.1 +/- 1.5 mumol/g protein) in cataractous lenses than in control lenses (10.0 +/- 1.0 mumol/g protein). Malondialdehyde, an indicator of lipid peroxidation, was higher (36.6 +/- 5.0 mumol/g protein) in lens-containing opacifications than in noncataractous lenses (10.1 +/- 1.9 mumol/gm protein) (p < 0.01). The levels of malondialdehyde suggest that lipid peroxidation was increased in the process of sugar cataractogenesis. The malondialdehyde content of all the lenses correlated inversely (r = -0.53, p < 0.01) with the coincident lens taurine levels. Taurine appears to protect the lens against the development of sugar cataracts; its inverse relationship with lens malondialdehyde suggests this is an antioxidant effect.
J Diabetes Complications
PMID:Taurine prevents galactose-induced cataracts. 848 50

We studied the functional consequences of an enhanced polyol pathway activity, elicited with galactose feeding, on the peripheral nerve of transgenic mice expressing human aldose reductase. Nontransgenic littermate mice were used as controls. With a quantitative immunoassay, the expression level of human aldose reductase in the sciatic nerve was 791 +/- 44 ng/mg protein (mean +/- SE), about 25% of that in human sural nerve. When the transgenic mice were fed food containing 30% galactose, significant levels of galactitol accumulated in the sciatic nerve. Galactose feeding of nontransgenic littermate mice led to a 10-fold lower accumulation of galactitol. Galactose feeding for 16 weeks caused a significant and progressive decrease in motor nerve conduction velocity in transgenic mice to 80% of the level of galactose-fed littermate mice, which was not significantly different from that of galactose-free littermate mice. A morphometric analysis of sciatic nerve detected > 10% reduction of mean myelinated fiber size but no alterations of myelinated fiber density in galactose-fed transgenic mice compared with other groups. The functional and structural changes that develop in galactose-fed transgenic mice are similar to those previously reported in diabetic animals. The results of these studies suggest that transgenic mice expressing human aldose reductase may be a useful model not only for defining the role of the polyol pathway in diabetic neuropathy but also for identifying and characterizing effective inhibitors specific for human aldose reductase.
Diabetes 1996 Jan
PMID:Galactosemic neuropathy in transgenic mice for human aldose reductase. 852 60

Many patients with diabetes mellitus show a moderate reduction in bone mass. Our recent in vitro studies showed that sustained exposure of osteoblast-like MG-63 cells to high glucose by itself impairs their functions partly via the polyol pathway. To investigate the role of hyperglycemia in the etiology of diabetic osteopenia in vivo separately from insulin deficiency, we determined whether epalrestat, an aldose reductase (AR) inhibitor (ARI), lessens the abnormalities in calcium (Ca) metabolism in galactose-fed rats. Weight gain was impaired in the rats, which was not altered by epalrestat. Galactose feeding temporarily enhanced bone resorption as reflected by increased biochemical markers for bone resorption (urinary excretion of pyridinoline [PYR] and deoxypyridinoline [DPYR]) at 1 to 3 months, which were significantly decreased by epalrestat. Epalrestat also restored the positive correlation between a bone-formation marker (serum osteocalcin [OC]) and a bone-resorption marker (urinary DPYR excretion) at 6.5 months. Histomorphometric analysis of bone performed 6.5 months after galactose feeding showed that both the bone volume and osteoblast numbers in the tibia, which were significantly suppressed by galactose feeding, were partly restored to a significant extent by the simultaneous administration of epalrestat. In summary, epalrestat partially protected against the development of osteoblast dysfunction and reduced the temporary increase in biochemical markers for bone resorption induced by galactose feeding, with a resultant increase in bone volume, suggesting that the polyol pathway may be intimately involved in the development of abnormal bone metabolism in galactose-fed rats.
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PMID:Protective effect of an aldose reductase inhibitor against bone loss in galactose-fed rats: possible involvement of the polyol pathway in bone metabolism. 1042 Dec 34

The influence of diets containing gamma-linolenic acid (GLA; 18:3n-6) on sciatic nerve conduction velocity (NCV) was determined in diabetic rats. NCV was lower in diabetic rats fed diets supplemented with olive oil or sunflower seed oil than in nondiabetic rats; rats supplemented with GLA during a 5-wk diabetic period, however, did not exhibit significantly lower NCV. The mean proportion of the phospholipid fatty acid linoleic acid (18:2n-6) was higher in the sciatic nerves of diabetic rats than in the nondiabetic groups irrespective of dietary lipid treatment. Additionally, the proportion of linoleic acid was higher in the diabetic rats fed sunflower oil than in all other groups. Dietary GLA supplementation did not significantly influence the fatty acid composition of nerve membrane phospholipids and there was no obvious correlation between the fatty acid composition of nerve membrane phospholipids and NCV. The content of fructose and glucose in sciatic nerves was higher, whereas that of myo-inositol was lower, in diabetic rats than in nondiabetic rats; however, this was not significantly influenced by dietary GLA. GLA administration did not significantly influence Na(+)-K(+)-exchanging ATPase or ouabain binding activity in sciatic nerve preparations, both of which remained nonsignificantly different in the diabetic and nondiabetic groups. The results suggest that dietary GLA can prevent the deficit in NCV induced by diabetes and that this effect is independent of the nerve phospholipid fatty acid profile, sugar and polyol content, Na(+)-K(+)-exchanging ATPase activity, and ouabain binding. GLA may prevent the deficit in NCV indirectly, possibly by its role as a precursor of vasodilatory prostaglandins. These results confirm that GLA is the active component of evening primrose oil.
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PMID:Prevention of nerve conduction deficit in diabetic rats by polyunsaturated fatty acids. 1061 2

Several studies have shown that the activities of delta-6-desaturase and delta-5-desaturase are depressed in experimental diabetes and in humans with insulin- and non-insulin-dependent diabetes mellitus (type I and type II diabetes mellitus respectively). Furthermore, treatment with insulin is known to correct the defects in desaturases in rats and humans with diabetes, especially in type I. In a recent study, we demonstrated that L-arginine and nitric oxide can prevent alloxan-induced beta cell damage, and the severity of diabetes, and restore the antioxidant status to near normal levels. But, no information is available as to the relationship between L-arginine-nitric oxide system and the metabolism of essential fatty acids in diabetes mellitus. In the present study, it was noted that the plasma levels of saturated fatty acids: stearic and palmitic were increased where as unsaturated fatty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced diabetic rats. In the liver phospholipid (PL) fraction, GLA, DGLA (dihomo-GLA) and alpha-linolenic acid (ALA) were decreased in the alloxan-treated group; in the muscle PL fraction, LA, GLA and DGLA were low, whereas an increase in the saturated fatty acid content was noted. L-arginine (the precursor of nitric oxide) and sodium nitroprusside (a nitric oxide donor) treatment of alloxan-induced diabetic rats enhanced the levels of LA, GLA and DGLA. Further, nitric oxide synthase inhibitor, L-NMMA, prevented this beneficial action of L-arginine-nitric oxide system on essential fatty acid metabolism. The abnormalities in the essential fatty acid metabolism observed also reverted to normalcy following control of diabetes with insulin. These results indicate that nitric oxide can enhance the activities of delta-6- and delta-5 desaturases, which are depressed in diabetes, and suggests that there is a close interaction between L-arginine-nitric oxide system and the metabolism of essential fatty acids.
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PMID:Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. 1076 77

The relative importance of sorbitol formation versus nonenzymatic glycosylation and advanced glycosylation end products (AGEs) on sugar cataract formation was examined in diabetic rats. Diabetes was experimentally induced in young, 50 g rats with streptozotocin, and aldose reductase inhibitors were administered in the diet for up to 8 weeks at concentrations of 0.06% for tolrestat or ponalrestat and 0.0125% for AL-1576. Cataract formation was monitored by hand-held slit lamp for up to 11 weeks. Lens polyol levels were monitored by GLC, glycosylated protein levels were spectrophotometrically determined, and AGE products were estimated by fluorescence measurements and ELISA. Sugar cataract formation was observed in all untreated diabetic rats while cataract formation was inhibited in all diabetic rats treated with the AR inhibitors. Lens sorbitol levels were reduced in all ARI-treated rats. Glycosylated lens protein levels were elevated in the diabetic rats, and these levels were not significantly lower in the non-cataractous lenses from ARI-treated diabetic rats. Fluorescence measurements of the lens proteins revealed increased lens AGE levels in all diabetic rats, and these were slightly reduced in the aldose reductase inhibitor treated diabetics. With ELISA, immunoreactive AGEs were only detected in cataractous lenses from the untreated diabetic rats. Immunoreactive AGEs were not detected in the clear lenses of the aldose reductase inhibitor treated diabetics or in the non-diabetic controls. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalyzed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.
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PMID:Relative importance of aldose reductase versus nonenzymatic glycosylation on sugar cataract formation in diabetic rats. 1080 25


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