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 promoter region of the human insulin-receptor (HINSR) gene was isolated from a human chromosome 19 bacteriophage library. With S1 nuclease mapping and primer-extension analysis, we identified multiple transcription-initiation sites. Dexamethasone, a known inducer of HINSR transcription, enhanced transcription of all major transcription-initiation sites. DNA sequence analysis indicated that the HINSR promoter has neither a TATA box nor a CAAT box. The HINSR promoter region contains six GGGCGG sequences that may be binding sites for the transcription factor Sp1. In addition, there were three TCCC sequences that were putative promoter regulatory regions. The HINSR gene promoter has structural similarity to the epidermal growth factor receptor gene promoter and has some features of the promoter of the meglutol (hydroxymethylglutaryl, HMG) CoA reductase gene and the early promoter of simian virus 40.
Diabetes 1988 Sep
PMID:Sequence and analysis of promoter region of human insulin-receptor gene. 341 Jan 65

Diabetes mellitus is known to affect drug and steroid metabolism in the rat liver. Recently it has been shown that the effect on drug metabolism is both transient and sex-dependent. This study shows that the effect of diabetes on steroid metabolism is also sex-dependent i.e. only seen in the male and the effect is always to abolish the sex differences in steroid metabolism found in the intact animals. 7 alpha-hydroxylase activity, which is higher in the female, is increased by diabetes in the male whereas 6 beta-hydroxylase, 16 alpha-hydroxylase and 17-oxosteroid reductase, which are all higher in the male, are decreased by diabetes. This is a very similar result to that found for drug metabolism and indicates that insulin plays a role in the maintenance of sex differences in hepatic steroid metabolism in the rat as it does for drug metabolism.
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PMID:Sex-dependent effect of streptozotocin-induced diabetes mellitus on hepatic steroid metabolism in the rat. 345 87

To study the effect of sorbinil on the alteration of the blood-retinal barrier, 32 adult-onset, non-insulin-dependent diabetic patients with minimal or no retinopathy were randomly assigned to receive either oral sorbinil (250 mg once a day) or a placebo for 6 mo. All patients underwent fundus photography, fluorescein angiography, and vitreous fluorophotometry before treatment and at 3 and 6 mo after treatment. Vitreous fluorophotometry data showed that the alteration of the blood-retinal barrier increased significantly less in the sorbinil-treated group compared with the placebo group during the 6-mo study period. Side effects were limited to hypersensitivity reactions, with skin rash and fever, in only 2 of the 16 patients who received the drug. These hypersensitivity reactions disappeared with discontinuation of the medication. Aldose-reductase inhibition may play an important role in stabilization of the blood-retinal barrier in early diabetic retinopathy.
Diabetes 1986 May
PMID:Effect of sorbinil on blood-retinal barrier in early diabetic retinopathy. 351 33

Alterations in endogenous free radical-scavenging defense mechanisms of rat tissues after body weight loss (induced by starvation for 72 h) associated with hypoinsulinemia were investigated. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione (GSSG) reductase as well as levels of reduced glutathione (GSH) were examined in several tissues and in erythrocytes. A complex pattern of changes was observed. CAT activities were increased in the heart and pancreas and decreased in the liver. SOD levels were decreased in the heart and increased in the kidney and pancreas. GSH-PX activities were increased only in the kidney, and levels of GSH were decreased only in the liver of starved animals. Erythrocytes from starved animals showed no alterations in the levels of major free radical-scavenging enzymes. However, GSSG reductase levels were lower in erythrocytes from starved animals, and this was associated with an increased susceptibility to H2O2-induced GSH depletion. Paradoxically, H2O2-induced malondialdehyde (MDA) production in erythrocytes from starved animals was lower than that in control erythrocytes. Our results suggest that, in studies of experimental diabetes, attention must be given to the influence of body weight loss per se on the biochemical alterations associated with this disease.
Diabetes 1987 Feb
PMID:Starvation-related alterations in free radical tissue defense mechanisms in rats. 380 31

The expressed and total activities of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase (EC 1.1.1.34) were measured in microsomal fractions prepared from cold-clamped liver samples [Easom & Zammit (1984) Biochem. J. 220, 733-738] from control or insulin-treated diabetic animals. Streptozotocin-induced diabetes resulted in a marked decrease in total activity of HMG-CoA reductase and in the fraction of the enzyme in the active form, but appreciable effects were only observed in the liver of animals in which the blood glucose was above 20 mM. Intravenous infusion of insulin into diabetic rats resulted in a rapid (less than 20 min) and total dephosphorylation of the enzyme in vivo without any change in total activity. Longer-term (4 h) treatment with insulin (injected intraperitoneally) produced a rapid increase in expressed/total HMG-CoA reductase activity ratio to about 90%, followed, after a lag of 2-3 h, by a 5-6-fold increase in total activity. These observations are discussed with respect to the possible role of insulin in generating and maintaining the respective diurnal rhythms in total and in expressed/total HMG-CoA reductase activity ratio observed for normal animals in vivo [Easom & Zammit (1984) Biochem. J. 220, 739-745].
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PMID:Effects of diabetes on the expressed and total activities of 3-hydroxy-3-methylglutaryl-CoA reductase in rat liver in vivo. Reversal by insulin treatment. 390 28

Temporal and spatial patterns of lipid deposition, vascularization and collagen deposition were described for subcutaneous adipose tissue in the fetal pig. Enzyme cytochemical changes were reported as they relate to the morphological differentiation of the subcutaneous depot. There are distinct temporal lags between the appearance of specific enzymes in adipocytes. For example, NADH-tetrazolium reductase activity appeared earliest whereas esterase activity appeared before lipoprotein lipase (LPL) activity. Adipose tissue primordia has been localized around specific tissue components in rat and pig tissues. These tissue components include hair follicles, sweat glands, large nerves, large blood vessels and mammary gland ducts. Lipid and enzyme cytochemistry demonstrates physical continuity between primordial cells and differentiated fat cell clusters. Alterations in maternal and/or fetal endocrine or metabolic profiles result in specific changes in fetal subcutaneous adipocytes. For example, maternal diabetes significantly increases cell size whereas genetic obesity has little effect on cell size but increases cellular LPL activity significantly. A comparison of subcutaneous and perirenal depots in the pig fetus indicated several depot specific anatomical and enzyme histochemical traits. Blood vessel architecture and vascular alkaline phosphatase activity clearly demarcated perirenal and subcutaneous depots in the fetus. These data indicate that site to site variations of adipose tissue characteristics may be reflecting intrinsic stromal-vascular aspects of specific locations.
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PMID:Anatomical and enzyme histochemical differentiation of adipose tissue. 393 90

It is known that dehydroascorbic acid (DHAA) produces a diabetogenic effect and its content in the blood increases in diabetes mellitus. It was previously established that the generation of reducing equivalents (RE) in the course of hexosemonophosphate shunt, CO2 production and SH-glutathione regeneration in erythrocytes with and without moderate and maximum oxidation load in vitro were not disturbed in diabetes. The authors have proposed a procedure to study blood and erythrocyte DHAA reductase activity in suspension in health and in insulin-dependent diabetes mellitus by means of redoxstatometry using a device of original design. A significant acceleration of RE transfer through the erythrocyte membrane was detected in diabetes. A lowered participation in this process of the AA in equilibrium DHAA "shuttle" system was recorded in the blood of patients with diabetes mellitus what was mostly expressed under the conditions of acidosis in vitro. Probably "shuttle" function in diabetes was provided by some other redox system which might be located in the plasma. The predominant functioning of this redox system and a decrease of DHAA reductase activity in diabetes resulted in the accumulation of DHAA in the blood of patients with type I diabetes mellitus.
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PMID:[Cause of dehydroascorbic acid accumulation in the blood of patients with insulin-dependent diabetes mellitus]. 398 93

Atherosclerosis, coronary artery disease and elevated serum cholesterol are frequently associated with an abnormal pattern of androgen metabolites, especially an elevation of etiocholanolone (E) and/or epiandrosterone (EA) relative to androsterone (A). Therapeutic correction of these metabolic defects may lower serum cholesterol. We have attempted to reproduce this metabolic syndrome in rats by altering their endocrine status. Intact male rats excreted very little A or E in their bile; more than 80% of the [4-14C]A-dione was excreted as unknown polar compounds. Adrenalectomy, thyroidectomy or streptozotocin diabetes induced little or no change in the excretion of both E and A and did not alter the A/E ratio. Hypophysectomy (hypox), however, resulted in a huge increase in E excretion and a 10-fold decrease in the A/E ratio. Treatment of hypophysectomized males with bovine growth hormone (bGH) but not testosterone or thyroxine restored the pattern of androgen metabolites to that of intact male rats. Intact female rats excreted mainly A, and this was decreased by ovariectomy. Hypophysectomy, however, resulted in a marked increase in E and a corresponding large decrease in A excretion. Treatment of hypox females with estradiol or triiodothyronine did not correct the metabolic defects in A and E production, whereas GH resulted in a pattern of A-dione metabolism resembling that of intact males; i.e., primarily polar metabolites with low A and E. Hypophysectomy thus results in a dramatic increase in 5 beta-reductase activity in male and female rats. GH therapy restores the metabolic pathway to that seen in intact males. Our objective had been to find a model capable of detecting substances which would increase A and decrease E production. The male rat (regardless of endocrine status) has little 5 alpha-reductase activity. The intact female rat, however, has high 5 alpha-reductase activity, and retains significant 5 alpha-reductase in the absence of the ovaries. In hypox females, 5 alpha-reductase was much reduced while 5 beta-reductase was increased. Furthermore, serum cholesterol was elevated in hypox females but could be lowered by exogenous androsterone. Thus the hypox female rat appears to offer the best model for identifying non-hormonal agents which could enhance the production of A and/or decrease the production of E. Such agents might favorably influence cholesterol metabolism.
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PMID:Effects of altered endocrine function on biliary metabolites of [4-14C]androst-4-ene-3,17-dione in rats. Possible utility as a model for identifying anti-atherosclerotic agents. 399 76

The activities of beta-Hydroxy-beta-methylglutaryl CoA reductase (HMG CoA reductase), Acyl CoA: Cholesterol-O-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase, the major enzymes involved in cholesterol metabolism, were determined in diabetic and non-diabetic rats after vagotomy and compared with those of sham-operated controls. Hepatic cholesterol levels and serum lipid profiles were also examined. In the non-diabetic animals vagotomy produced a significant increase in HMG CoA reductase (the rate limiting enzyme of cholesterol biosynthesis), and ACAT (the enzyme responsible for intracellular esterification) activities, while the activity of cholesterol 7 alpha-hydroxylase (which catalyses the rate determining step of bile acid biosynthesis) was significantly decreased. These rats had higher levels of free and esterified cholesterol in the liver and serum cholesterol levels were also increased in comparison with sham-operated animals. Vagotomized diabetic rats had similar HMG CoA reductase activity, but significantly reduced ACAT and reduced cholesterol 7 alpha-hydroxylase activity in comparison with sham-operated diabetic rats. There were significant alterations in hepatic and serum cholesterol fractions in both normal and diabetic rats after vagotomy. The results suggest that vagotomy leads to an increased rate of cholesterol synthesis and a decreased rate of cholesterol utilization, thus providing a possible mechanism for excessive cholesterol accumulation. These results are discussed in relation to alterations in cholesterol metabolism found in diabetic autonomic neuropathy.
Diabetes Res 1985 Nov
PMID:Cholesterol metabolism: regulatory effects of the vagus in the normal and diabetic animal. 407

In the present work it was observed that the diabetic state alters the hypophyseal response to castration, without the expected increase in the LH serum levels, as found in the control rats. On the other hand, the stimulation of the hypophysis with LHRH resulted in a lower response in the case of the diabetic animal. The results presented herein are in good agreement with the finding of a reduction in the number of androgen binding sites and also with a diminished activity of the 5 alpha-reductase in the hypophysis from diabetic animals. The present results indicate an alteration in the hypophyseal gonadotropin production as well as in the overall process of hypophyseal response in experimental diabetes.
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PMID:Hypothalamic-hypophyseal-gonadal axis in the streptozotocin-induced diabetic male rat. 636 95


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