Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty seven subjects with Type II diabetes mellitus underwent analysis of the Self-Administered Alcoholism Screening Test (SAAST) and hemoglobin associated acetaldehyde levels (HbAA). The SAAST scores and HbAA levels correlated with one another (r = .48, p = 0.009). No correlation between glycated hemoglobin levels (GHb) and HbAA levels or SAAST was found. Glucose incubation of whole blood led to an increase in GHb but no change in HbAA. We conclude that HbAA and SAAST correlate with each other when measured in patients with diabetes. Therefore each test appears clinically useful in quantifying alcohol consumption in individuals with Type II diabetes mellitus.
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PMID:Hemoglobin associated acetaldehyde correlates with the Self-Administered Alcoholism Screening Test but not glycated hemoglobin in type II diabetes mellitus. 206 32

In Japanese type 2 diabetes, which occupies more than 95%, it is an increasingly important problem as a life-style related disease. The total diabetic population is estimated as approximately 7 million with a prevalence of approximately 6%. Along with genetically low postprandial insulin secretion, they are found to be less tolerable to being overweight to develop insulin resistance. The body weight change in the prediabetic era consisting of 508 male patients treated on their diet alone was reviewed and it was found that a few kilograms of weight gain could be a cause of insulin resistance. Moreover, inactive aldehyde dehydrogenese 2 (ALDH2), which is common in Japanese, is found to be a factor in the development of hyperglycemia. In 163 diabetics, HbAlc of the inactive ALDH2 group was 8.1+/-1.3, while that of active ALDH2 was 7.5+/-0.9% (P<0.05) in a light, social drinking group. However, Japanese type 2 diabetes is also changing. In recent years, the data from a 75-g oral glucose tolerance test of 2121 clients showed that insulinogenic index of clients with impaired glucose tolerance was similar to that of a normal glucose tolerance group and that the area under the insulin curve (AUC) was high in younger diabetics. From a life-style modification perspective, the importance of body weight control by diet and exercise as well as refraining from excessive drinking should be emphasized.
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PMID:Genetic and environmental interaction in Japanese type 2 diabetics. 1102 79

In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 "activity" and ADH2 "superactivity." The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.
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PMID:ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes. 1531 96

Findings obtained from numerous prospective cohort and case-control studies on alcohol consumption and pancreatic cancer risk have been inconsistent, with many confounding variables present in various investigations. However, heavy alcohol consumption has been known to be a major cause of chronic pancreatitis and a risk factor for type 2 diabetes mellitus, both of which are linked to pancreatic cancer. It has been established that an extensive normal interaction exists between the exocrine and endocrine pancreas, as well as in inflammatory processes and carcinogenesis. Alcohol and its metabolites (acetaldehyde and fatty acid ethyl esters) can alter metabolic pathways involved in the inflammatory response and carcinogenesis, and they are mediated by one or more of the following mechanisms: (1) premature activation of zymogens; (2) induction of the inflammatory response through activation of nuclear transcription factors, including nuclear factor-kappa and activation protein 1; (3) increased production of reactive oxygen species, resulting in oxidative DNA damage and altered effect of dietary antioxidants; (4) activation of pancreatic stellate cells, which leads to fibrosis; (5) gene mutation in enzymes related to cytochrome P450, glutathione S-transferase, aldehyde dehydrogenase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor; (6) synergistic effects of ethanol and tobacco carcinogen on NNK [nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] metabolism; and (7) dysregulation of proliferation and apoptosis. These various metabolic effects of alcohol can lead to or interact with other risk factors (genetic, dietary, environmental, and lifestyle factors) that result in acute and chronic pancreatitis and diabetes mellitus and, ultimately, affect the multistep process of carcinogenesis toward the development of pancreatic cancer.
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PMID:Alcohol and pancreatic cancer. 1605 82

We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus.
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PMID:Oxidative stress in atherosclerosis and diabetes. 1625 16

Ethanol has been considered as a lifestyle factor that may influence the risk of type 2 diabetes mellitus. In healthy adults, acute ethanol consumption results in insulin resistance. Acute ethanol consumption causes insulin resistance selectively in skeletal muscle by an indirect mechanism. Possible mediators include triglycerides (TGs), catecholamines, acetaldehyde, alterations in insulin binding, and hepatic insulin sensitizing substance (HISS). Recent studies in rats showed that acute administration of ethanol causes insulin resistance in a dose-dependent manner that is secondary to the blockade of insulin-induced HISS release. Chronic ethanol consumption may improve insulin sensitivity, but the results from the randomized controlled trials are mixed. Differences in ethanol dose, consumption period, and abstention period may account for the discrepant results. Epidemiological studies have suggested that the relationship between ethanol and insulin sensitivity is either an inverted U-shape or a positive linear relationship. Future randomized controlled trials should consider the dose of ethanol and the duration of ethanol consumption and abstention in the experimental design. Chronic prenatal and postnatal (nursing) ethanol exposure results in insulin resistance that is secondary to the absence of HISS release/action with the HISS-independent insulin action and insulin-like growth factor-1 (IGF-1)-mediated glucose disposal action remaining unimpaired. The impaired HISS release may be related to a reduction in hepatic glutathione (GSH) levels. The effect of chronic ethanol consumption on HISS has not been evaluated.
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PMID:The effect of acute, chronic, and prenatal ethanol exposure on insulin sensitivity. 1631 Feb 55

Biological properties of renal-specific oxidoreductase (RSOR), characteristics of its promoter, and underlying mechanisms regulating its expression in diabetes were analyzed. RSOR expression, normally confined to the renal cortex, was markedly increased and extended into the outer medullary tubules in db/db mice, a model of type 2 diabetes. Exposure of LLCPK cells to d-glucose resulted in a dose-dependent increase in RSOR expression and its enzymatic activity. The latter was related to one of the glycolytic enzymes, myo-inositol oxygenase. The increase in activity was in proportion to serum glucose concentration. The RSOR expression also increased in cells treated with various organic osmolytes, e.g., sorbitol, myoinositol, and glycerolphosphoryl-choline and H(2)O(2). Basal promoter activity was confined to -1,252 bp upstream of ATG, and it increased with the treatment of high glucose and osmolytes. EMSAs indicated an increased binding activity with osmotic-, carbohydrate-, and oxidant-response elements in cells treated with high glucose and was abolished by competitors. Supershifts, detected by anti-nuclear factor of activated T cells, and carbohydrate-response-element-binding protein established the binding specificity. Nuclear factor of activated T cells tonicity-enhancer-binding protein and carbohydrate-response-element-binding protein had increased nuclear expression in cells treated with high glucose. The activity of osmotic-response element exhibited a unique alternate binding pattern, as yet unreported in osmoregulatory genes. Data indicate that RSOR activity is modulated by diverse mechanisms, and it is endowed with dual properties to channel glucose intermediaries, characteristic of hepatic aldehyde reductases, and to maintain osmoregulation, a function of renal medullary genes, e.g., aldose reductase, in diabetes.
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PMID:Modulation of renal-specific oxidoreductase/myo-inositol oxygenase by high-glucose ambience. 1633 Jul 53

Hepatocellular cancer is the fifth most frequent cancer in men and the eighth in women worldwide. Established risk factors are chronic hepatitis B and C infection, chronic heavy alcohol consumption, obesity and type 2 diabetes, tobacco use, use of oral contraceptives, and aflatoxin-contaminated food. Almost 90% of all hepatocellular carcinomas develop in cirrhotic livers. In Western countries, attributable risks are highest for cirrhosis due to chronic alcohol abuse and viral hepatitis B and C infection. Among those with alcoholic cirrhosis, the annual incidence of hepatocellular cancer is 1-2%. An important mechanism implicated in alcohol-related hepatocarcinogenesis is oxidative stress from alcohol metabolism, inflammation, and increased iron storage. Ethanol-induced cytochrome P-450 2E1 produces various reactive oxygen species, leading to the formation of lipid peroxides such as 4-hydroxy-nonenal. Furthermore, alcohol impairs the antioxidant defense system, resulting in mitochondrial damage and apoptosis. Chronic alcohol exposure elicits hepatocyte hyperregeneration due to the activation of survival factors and interference with retinoid metabolism. Direct DNA damage results from acetaldehyde, which can bind to DNA, inhibit DNA repair systems, and lead to the formation of carcinogenic exocyclic DNA etheno adducts. Finally, chronic alcohol abuse interferes with methyl group transfer and may thereby alter gene expression.
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PMID:Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. 1660 31

Alcohol intake is one of the important lifestyle factors for the risk of insulin resistance and type 2 diabetes. Acetaldehyde, the major ethanol metabolite which is far more reactive than ethanol, has been postulated to participate in alcohol-induced tissue injury although its direct impact on insulin signaling is unclear. This study was designed to examine the effect of acetaldehyde on glucose uptake and insulin signaling in human dopaminergic SH-SY5Y cells. Akt, mammalian target of rapamycin (mTOR), ribosomal-S6 kinase (p70(S6K)), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) and insulin receptor substrate (IRS)-2 were evaluated by Western blot analysis. Glucose uptake and apoptosis were measured using [(3)H]-2-deoxyglucose uptake and caspase-3 assay, respectively. Short-term exposure (12 h) of acetaldehyde (150 muM) facilitated glucose uptake in a rapamycin-dependent manner without affecting apoptosis, IRS-2 expression and insulin-stimulated glucose uptake in SH-SY5Y cells. Acetaldehyde suppressed basal and insulin-stimulated Akt phosphorylation without affecting total Akt expression. Acetaldehyde inhibited mTOR phosphorylation without affecting total mTOR and insulin-elicited response on mTOR phosphorylation. Rapamycin, which inhibits mTOR leading to inactivation of p70(S6K), did not affect acetaldehyde-induced inhibition on phosphorylation of Akt and mTOR. Interestingly, acetaldehyde enhanced p70(S6K) activation and depressed 4E-BP1 phosphorylation, the effect of which was blunted and exaggerated, respectively, by rapamycin. Collectively, these data suggested that acetaldehyde did not adversely affect glucose uptake despite inhibition of insulin signaling cascade at the levels of Akt and mTOR, possibly due to presence of certain mechanism(s) responsible for enhanced p70(S6K) phosphorylation.
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PMID:Acetaldehyde promotes rapamycin-dependent activation of p70(S6K) and glucose uptake despite inhibition of Akt and mTOR in dopaminergic SH-SY5Y human neuroblastoma cells. 1696

Zuni Indians are experiencing simultaneous epidemics of type 2 diabetes mellitus (T2DM) and renal disease [Scavini, M., Stidley, C. A., Shah, V. O., Narva, A. S., Tentori, F., Kessler, D. S., et al. (2003). Prevalence of diabetes is higher among female than male Zuni Indians: Diabetes among Zuni Indians. Diabetes Care, 26 (1), 55-60; Shah, V. O., Scavini, M., Stidley, C., Tentori, F., Welty, T., Maccluer, J. W., et al. (2003). Epidemic of diabetic and nondiabetic renal disease among the Zuni Indians: The Zuni Kidney Project. Journal of the American Society of Nephrology, 14, 1320-1329]. Methylglyoxal (MG), a highly reactive, cytotoxic, cross-linking endogenous aldehyde involved in the modification of biologic macromolecules, is elevated among patients with T2DM. Glyoxalase I (Glo1) is the initial enzyme involved in the detoxification of MG. Glo1 is a dimeric enzyme with three isoforms Glo1-1, Glo2-1, and Glo2-2, resulting from a point mutation (A-->C) at position 332 of cDNA. The present study was conducted to explore the hypothesis that specific polymorphisms of the Glo1 gene are associated with diabetes and/or albuminuria in Zuni Indians. We studied four groups of Zuni Indians stratified by diabetes status and albuminuria, as assessed by the urinary albumin:creatinine ratio (UACR): Group I--normal controls; Group II--T2DM and UACR<0.03; Group III--T2DM and UACR>or=0.03; and Group IV--nondiabetic participants with UACR>or=0.03. Genomic DNA was used as template for polymerase chain reaction amplification of the Glo1 gene. Products were digested to yield 110-bp bands (homozygous, CC); 54- and 45-bp bands (homozygous, AA); or all three bands (heterozygous CA). Data on age, gender, UACR, serum creatinine, hemoglobin A1(c), serum glucose, systolic and diastolic blood pressures, and the duration of T2DM among participants in Groups II and III were analyzed using analysis of variance. A generalized linear model logistic regression analysis was used to assess the relationships between specific Glo1 polymorphisms to T2DM and UACR. All three Glo1 genotypes were present among Zuni Indians. There were no significant differences in the distributions of Glo1 genotypes among the study groups (chi-square test, P=.5590). The prevalence of Glo1 A allele was higher among diabetic participants (Groups II and III combined) than among nondiabetic participants (Groups I and IV combined) (chi-square test, P=.0233). There was an association (odds ratio=2.9; 95% confidence interval=1.3-7.2) between the Glo1 A allele and T2DM.
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PMID:Distribution of glyoxalase I polymorphism among Zuni Indians: the Zuni Kidney Project. 1841 87


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