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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sorption capacity, the content of catecholamines, cytochrome C, the activity of cytochromoxidase, of some tricarbonic acids cycle enzymes were studied in the myocardium of rabbits with dithizone diabetes of moderate severity. The detected electrocardiographic changes, hypoxia, disturbances of the hormone-mediator-enzymatic metabolism an increased affinity to the myocardial cell stain at the early periods of diabetes mellitus development permitted to regard cardiovascular affections in diabetes mellitus as a manifestation, not as a complication of the disease.
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PMID:[Changes in the myocardium during the early stages of dithizone diabetes development]. 41 89

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes.
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PMID:Diabetes secondary to genetic disorders. 144 74

Diabetes in the non-obese diabetic (NOD) mouse is a multigenic autoimmune disease and is possibly controlled by three recessive loci, including one that is linked to the major histocompatibility complex (MHC). The first external domain of the Class II MHC I-A beta chain in these mice is unique and has been suggested as being responsible for autoimmunity. The I-A alpha chain in these mice is I-A alpha d, and they lack the expression of I-E molecules. We have investigated immune responses to various Ir gene control antigens in NOD mice to determine the influence of the NOD Ia and particularly the I-A beta chain. We find that sheep insulin is highly immunogenic while other insulins are weakly immunogenic in these mice. Hen egg lysozyme, pigeon cytochrome C and the synthetic polypeptide Poly 18, Poly EYK(EYA)5 antigen produce good antibody responses. Apart from H-2d, NOD are the only mice where Poly 18 antigen is immunogenic. In these mice Poly 18 induced good T-cell proliferative response, which was inhibited by anti-Ia antibody, and the mice were able to respond to tyrosine-containing polypeptide Poly EYA but not to the phenylalanine-containing antigen Poly EFA. We also found that synthetic peptide 48-60 of the NOD I-A beta chain is highly immunogenic in syngeneic NOD mice both for T cells and B cells. Using an I-A beta chain-specific monoclonal antibody, we are able to prevent induction of diabetes when the antibody was administrated in prediabetic, young mice. Our results suggest that the immune response to various antigens and autoimmune diabetes in NOD mice is directly influenced by the I-A beta chain.
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PMID:Role of the first external domain of I-A beta chain in immune responses and diabetes in non-obese diabetic (NOD) mice. 170

Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
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PMID:Pharmacokinetics of caffeine in patients with decompensated type I and type II diabetes mellitus. 176 Oct 72

The effect of insulin-dependent diabetes on the hepatic microsomal activity of cytochrome P450III and P450IV family proteins was investigated in rats pretreated with streptozotocin. In order to discern between the effects of the diabetogen per se and those of the ensuing diabetes, streptozotocin-treated rats received in addition either nicotinamide to prevent the onset of diabetes or daily treatment with insulin to antagonize the effects of diabetes. Streptozotocin-treated rats displayed higher ethylmorphine and erythromycin N-demethylase activities and lauric acid hydroxylase activity. Increases were also detected immunologically by using monospecific polyclonal antibodies against the P450III and P450IV families. All effects were prevented by nicotinamide and effectively antagonized by insulin. In order to evaluate the role of the ketone bodies in the diabetes-induced increases in the above activities, rats were rendered hyperketonaemic by dietary administration of medium-chain triacylglycerols. These hyperketonaemic animals displayed high laurate hydroxylase activity and P450IV apoprotein levels, similar to those seen in the diabetic animals. Hyperketonaemia induced by dietary means caused a modest increase in the demethylation of erythromycin and had no significant effect on the N-demethylation of ethylmorphine. Furthermore, no marked increases were evident in the P450III apoprotein levels in the hyperketonaemic animals. It is concluded that insulin-dependent diabetes induces proteins of the P450III and P450IV families, and that the hyperketonaemia that accompanies diabetes is largely responsible for the changes in the latter family.
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PMID:Induction of cytochrome P450III and P450IV family proteins in streptozotocin-induced diabetes. 214 78

The effects of pituitary and pancreatic hormones on the change in hepatic cytochrome P450s were studied in alloxan- or streptozotocin-induced male rats. In two major sex-specific forms, P450-male and P450(6 beta-1), the former was decreased in chronic (5 week) diabetes to only less than one-third of controls and the latter was also reduced in early (1 week) diabetes. In contrast, a main phenobarbital-inducible form, P450b, was enhanced 25- to 30-fold in these diabetic rats. 3-Methylcholanthrene-inducible P448H was also elevated 3-fold in alloxan-induced diabetes. These changes in hepatic contents of P450-male, P450-6 beta-1, and P450b, which are under the regulation of pituitary growth hormone, associated well with the reported results of time-dependent changes in growth hormone levels in diabetes (G.S. Tannenbaum (1981) Endocrinology 108, 76-82), suggesting that the change in growth hormone level is a factor responsible for alterations in hepatic cytochrome P450s. Normalizing effects of insulin on these forms were also studied. Treatment of diabetic rats with insulin reversed the decreased amounts of both P450-male protein and mRNA. Insulin also normalized hepatic contents of P450b, P4506 beta-1, and P448H. However, the treatment of hypophysectomized rats with insulin had no effect, and treatment of diabetic rats with growth hormone or a suppressing agent of somatostatin, cysteamine, showed trivial effects on P450-male and P450b. These results suggest that insulin does not act directly as a substitute of growth hormone, but exerts its effect indirectly through the normalization of a growth hormone-mediated process(es) in diabetic rats.
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PMID:Cytochrome P450 in livers of diabetic rats: regulation by growth hormone and insulin. 252 54

The effects of streptozotocin-induced diabetes and fasting on hepatic cytochrome P-450 enzymes in sexually mature male rats were studied by immunochemical techniques and enzyme assays. The level of cytochrome P-450ac (an acetone/ethanol inducible form), 65 pmol/mg microsomal protein in control rats, increased 4- to 5-fold in diabetic rats and 3- and 5-fold in fasting rats. In contrast, P-450 UT-A (a male specific form) decreased drastically from 295 pmol/mg in the control group to about 10% of this value in diabetic rats and to 50% in fasting rats. P-450 PCN-E (a 16 alpha-cyanopregnenolone/dexamethasone inducible form), on the other hand, decreased from 151 pmol/mg to 38% in diabetic rats and increased 2-fold in fasting rats. These changes were also reflected in catalytic activities using N-nitrosodimethylamine, benzphetamine, and erythromycin as substrates. Slight changes in cytochromes P-450 UT-F, P-450 UT-I and P-450 PB-C were also observed under these conditions, but the biological significance is not known. These results suggest that different mechanisms exist for the regulation of the expression of cytochrome P-450 enzymes in diabetic and fasting rats.
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PMID:Similarities and differences in the regulation of hepatic cytochrome P-450 enzymes by diabetes and fasting in male rats. 281 18

Long-term cafeteria feeding, cold exposure, and the combination of treatments increased energy intake in female Wistar rats by 25%, 113%, and 150%, respectively, in comparison with controls (P less than 0.01). Although cafeteria feeding at room temperature markedly increased the insulin response to an intravenous glucose tolerance test (IVGTT), glucose tolerance was deteriorated (P less than 0.01). In contrast, cold exposure significantly improved glucose tolerance in the presence of a reduced insulin response in Purina- and cafeteria-fed animals. Moreover, cold exposure also decreased body weight gain and increased brown adipose tissue mass, total cytochrome-oxidase activity, and cellularity by approximately 600-800%. The results suggest that cold exposure enhances insulin sensitivity of peripheral tissues, whereas hyperphagia on a high-fat, low-protein diet leads to insulin resistance. In addition, the results demonstrate that prolonged stimulation of energy expenditure by cold exposure not only reverses the diabetogenic effects of cafeteria feeding but also improves glucose tolerance. This phenomenon could result from a combination of two factors: (1) a cold-induced prevention of obesity; and (2) an enhanced disposal of circulating glucose into peripheral tissues, including brown adipose tissue.
Diabetes 1986 Mar
PMID:Cold exposure reverses the diabetogenic effects of high-fat feeding. 300 94

Polyclonal antibodies were produced in rabbits against purified cytochrome P-450j isolated from isoniazid-treated adult male rats. The monospecificity of immunoadsorbed antibody to cytochrome P-450j was demonstrated by Ouchterlony double diffusion analyses, enzyme-linked immunosorbent assays, and immunoblots. Immunoquantitation results indicated that rat liver microsomal cytochrome P-450j content decreases between 3 and 6 weeks of age in both the male and female animal. Several xenobiotics, such as Aroclor 1254, mirex, and 3-methylcholanthrene, repressed cytochrome P-450j levels when administered to male rats. Isoniazid, dimethyl sulfoxide, pyrazole, 4-methylpyrazole, and ethanol were inducers of cytochrome P-450j in rat liver although these compounds showed different inducing potencies. Microsomes from adult male rats with chemically induced diabetes also contained elevated levels of cytochrome P-450j compared to untreated animals. Cytochrome P-450j levels were measurable in kidney, whereas this isozyme was barely detectable in lung, ovaries, and testes; however, extrahepatic cytochrome P-450j was inducible by isoniazid. Approximately 80-90% of microsomal N-nitrosodimethylamine demethylation was inhibited by antibody to cytochrome P-450j whether the microsomes were isolated from untreated rats or animals administered inducers or repressors of cytochrome P-450j. The residual catalytic activity resistant to antibody inhibition may be a reflection of the inaccessibility of a certain amount of cytochrome P-450j due to interference by NADPH-cytochrome P-450 reductase based on results obtained with the reconstituted system. There was a good correlation (r2 = 0.87) between cytochrome P-450j content and N-nitrosodimethylamine demethylase activity in microsomes from rats of different ages and treated with various xenobiotics. The evidence presented indicates that cytochrome P-450j is the primary, and perhaps sole, microsomal catalyst of N-nitrosodimethylamine demethylation at substrate concentrations relevant to hepatocarcinogenesis induced by N-nitrosodimethylamine.
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PMID:Regulation of cytochrome P-450j, a high-affinity N-nitrosodimethylamine demethylase, in rat hepatic microsomes. 311 78

Hepatic microsomal cytochrome P-450j has been studied using the male spontaneously diabetic BB rat as a model for insulin-dependent diabetes. This approach avoids any direct hepatotoxic effects from chemical diabetogenic agents. Both diabetic rats maintained on insulin and nondiabetic littermates were used as controls. Levels of cytochrome P-450j were increased approximately 3-fold in the diabetics 4 days after the cessation of insulin therapy. In addition, cytochrome P-450j-catalyzed enzymatic activities, aniline hydroxylation, and N-nitrosodimethylamine N-demethylation were increased by the diabetic state at this same time period. Cytochrome P-450f remained at control levels in all groups of animals. In order to test the hypothesis that ketone bodies are involved in the increase in cytochrome P-450j in the diabetic state, plasma beta-hydroxybutyrate levels were monitored. Hepatic aniline hydroxylation, N-nitrosodimethylamine N-demethylation, and cytochrome P-450j levels in individual animals were found to correlate with plasma beta-hydroxybutyrate levels (r = 0.59-0.71 p less than 0.001). In contrast, no significant correlation between levels of cytochrome P-450j and plasma glucose, insulin, or cholesterol was observed in individual animals (r = 0.07-0.23, p greater than 0.4). We conclude that cytochrome P-450j is induced in the livers of spontaneously diabetic rats, and that this induction may be associated directly or indirectly with elevated plasma ketone levels.
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PMID:Hepatic cytochrome P-450j induction in the spontaneously diabetic BB rat. 327 33


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