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)

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

Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells.
J Diabetes Complications
PMID:Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation. 1220 82

Dietary carbohydrate activates the sympathetic nervous system (SNS). As the mechanisms underlying this response are not fully characterized, studies were undertaken to compare SNS responses to ingestion of glucose, fructose, and galactose. SNS activity was examined using techniques of [(3)H]norepinephrine ([(3)H]NE) turnover in brown and white fat. In addition, gene expression for several sympathetically related proteins was also analyzed in these tissues. [(3)H]NE turnover in interscapular brown adipose tissue (IBAT) and retroperitoneal fat increased in response to glucose and fructose in the diet, whereas [(3)H]NE turnover in epididymal fat did not respond to either monosaccharide. Galactose feeding, by contrast, decreased [(3)H]NE turnover in IBAT, but increased it in epididymal, though not retroperitoneal, fat. Expression of GLUT4 was more abundant in IBAT and retroperitoneal fat from glucose- and fructose-fed animals than from diet- or galactose-fed rats. Chemical sympathectomy abolished the GLUT4 response in retroperitoneal fat, but was without effect on GLUT4 in epididymal fat. These studies are consistent with activation of a neural pathway by oral glucose or fructose, leading to SNS activation in IBAT and retroperitoneal fat and enhanced GLUT4 expression.
Diabetes 2004 May
PMID:Effects of dietary monosaccharides on sympathetic nervous system activity in adipose tissues of male rats. 1511 96

Dogs fed galactose develop diabetes-like ocular complications that include keratopathy, cataracts, and retinopathy. The purpose of this study was to investigate whether galactosemic dogs display reduced aqueous flow similar to that observed in patients with insulin-dependent diabetes mellitus. Twelve male beagles at 9 months of age were divided into three groups of four. The Galactose group was fed diet containing 30% galactose for 97 months and the Reversal group was fed the galactose diet for an initial 38 months then standard dog diet for the remaining period. The Control group was fed standard dog diet for 97 months. Aqueous flow was determined by fluorophotometry in one eye per dog at 96 and 97 months after the initiation of galactose feeding. Intraocular pressure (IOP) was measured once in the morning by pneumatonometry. Anterior chamber depth was measured by A-scan. At the end of the experiment, eyes were enucleated and processed for histological examination. Dogs fed galactose diet for 97 months had significantly (p<0.05) increased body weights but similar IOP and anterior chamber depth compared to the other groups, and significantly (p=0.05) reduced aqueous flow compared to the control group (4.4+/-2.2 vs. 6.8+/-2.4 microl/min, mean+/-standard deviation, respectively). Additionally, aqueous flow decreased in the Reversal group to 3.1+/-1.3 microl/min (p=0.002). This decrease correlated with morphological changes of the ciliary processes. Like patients with insulin-dependent diabetes mellitus, galactose-fed dogs demonstrate reduced aqueous flow. This reduction was irreversible and independent of the retinopathy present. This animal model may be useful for the study of aqueous humor dynamics in diabetes.
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PMID:Aqueous flow in galactose-fed dogs. 1679 6

Secondary active glucose transport occurs by at least four members of the SLC5 gene family. This review considers the structure and function of two premier members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and renal glucose reabsorption. Genetics disorders of SGLTs include Glucose-Galactose Malabsorption, and Familial Renal Glucosuria. SGLT1 plays a central role in Oral Rehydration Therapy used so effectively to treat secretory diarrhoea such as cholera. Increasing attention is being focused on SGLTs as drug targets for the therapy of diabetes.
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PMID:Active sugar transport in health and disease. 1722 66

Dysmetabolic state in diabetes may lead to augmented synthesis of extracellular matrix (ECM) proteins. In the endothelial cells, we have previously demonstrated that glucose-induced fibronectin (FN) production and that of its splice variant, EDB(+)FN, is regulated by protein kinase B (PKB, also known as Akt). In this study, we investigated the role of Akt1 in ECM protein production in the organs affected by chronic diabetic complications. We studied Akt1/PKBalpha knockout mice and wild-type control littermates. To avoid confounding effects of systemic insulin, we used 30% galactose feeding to induce hyperhexosemia for 8 wk starting at 6 wk of age. We investigated FN mRNA, EDB(+)FN mRNA, and transforming growth factor (TGF)-beta mRNA expression, Akt phosphorylation, Akt kinase activity, and NF-kappaB and AP-1 activation in the retina, heart, and kidney. Renal and cardiac tissues were histologically examined. Galactose feeding caused significant upregulation of FN, EDB(+)FN, and TGF-beta in all tissues. FN protein levels paralleled mRNA. Such upregulation were prevented in Akt1-deficient galactose-fed mice. Galactose feeding caused ECM protein deposition in the glomeruli and in the myocardium, which was prevented in the Akt knockout mice. NF-kappaB and AP-1 activation was pronounced in galactose-fed wild-type mice and prevented in the galactose-fed Akt1/PKBalpha-deficient group. In the retina and kidney, Ser473 was the predominant site for Akt phosphorylation, whereas in the heart it was Thr308. Parallel experiment in streptozotocin-induced diabetic animals showed similar results. The data from this study indicate that hyperhexosemia-induced Akt/PKB activation may be an important mechanism leading to NF-kappaB and AP-1 activation and increased ECM protein synthesis in the organs affected by chronic diabetic complications.
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PMID:Akt activation and augmented fibronectin production in hyperhexosemia. 1766 88

Blood galactose clearance after an intravenous galactose load has been widely used as a quantitative liver function test. We have developed a novel quantitative rat liver function test, the galactose single point (GSP) method, to assess residual liver function with various injuries by measuring single time point galactose concentration in blood after an intravenous bolus injection of galactose. The goal of this study was to evaluate the influence of nonhepatic factors such as hyperglycemia on GSP and galactose elimination capacity (GEC) in rats. Four groups of animal studies were carried out, as follows: (1) normal control (NC), (2) streptozotocin-induced diabetes (DM), (3) carbon tetrachloride-induced hepatotoxicity (CCl(4)), and (4) streptozotocin-induced diabetes with CCl(4)-induced hepatotoxicity (DM + CCl(4)). The serum glucose levels in the diabetic groups (DM and DM + CCl(4)) were significantly increased compared with the NC and CCl(4) groups (P < .001). A significant increase in hepatic activities of aspartate aminotransferase and alanine aminotransferase was observed in the CCl(4)-treated groups (CCl(4) and DM + CCl(4)) compared with the NC and DM groups (P < .001). In comparison with the NC group, the values of GSP and GEC in the diabetic groups (DM and DM + CCl(4)) were significantly reduced (P < .001) and increased (P < .01), respectively. Galactose single point had highly significant correlations with GEC (P < .001). These results suggest that galactose metabolism tests-as quantitative parameters of liver function-should be interpreted with caution in the condition of a significant hyperglycemia.
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PMID:Effects of hyperglycemia on quantitative liver functions by the galactose load test in diabetic rats. 1769 71


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