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 dawn phenomenon was evaluated in eight C-peptide-negative type I (insulin-dependent) diabetic patients on two occasions by measuring glucose concentrations every 30 min from 2400 to 0800 h while the subjects were receiving an insulin infusion (0.12 mU.kg-1.min-1). In random order at 2230 h, they orally received either a sleeping medication alone or with 5.0 mg methscopolamine bromide, an anticholinergic agent. The peak growth hormone (GH) concentrations (ng/ml +/- SE) after sleep were markedly inhibited by methscopolamine (4.7 +/- 2.6 vs. 23.0 +/- 9.2). During the control night, the late (0400-0800 h) glucose response (area under curve but above 0400 h value) was significantly higher (P less than .02) than the early (2400-0400 h) glucose response (area under curve but above 2400 h value). After methscopolamine, the early and late glucose responses were virtually identical. The anticholinergic agent did not affect glucagon levels, overnight urinary catecholamine excretion, or the diurnal cortisol concentrations. The total area under the free fatty acid (FFA) curves was significantly (P less than .05) reduced by methscopolamine. We conclude that sleep-induced GH secretion may cause the dawn phenomenon by increasing FFA levels. Oral administration of methscopolamine at bedtime is a simple pharmacological approach that could test the clinical importance of the dawn phenomenon.
Diabetes 1988 Feb
PMID:Suppression of sleep-induced growth hormone secretion by anticholinergic agent abolishes dawn phenomenon. 339 41

To extend previous studies on the apparent acceleration of collagen aging in diabetes mellitus, dura collagen from human adults of different ages, with and without diabetes, was processed to yield soluble and insoluble fractions. Insoluble fractions were cleaved by cyanogen bromide. Release of peptides from insoluble collagen by cyanogen bromide decreased markedly with age and was much less from the collagen of diabetics than from nondiabetics of similar ages. The acrylamide gel profiles of peptides released were similar, but not identical, for samples of different ages and for samples from diabetics. It was concluded that age-dependent and diabetes-dependent cross-linking was widespread throughout helical regions of collagen molecules and that collagen throughout the body is altered in diabetes. Analyses of fragments of insoluble collagen are required to gain information on the chemistry of the cross-links that form with aging and diabetes.
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PMID:Effects of age and diabetes mellitus on cyanogen bromide digestion of human dura mater collagen. 622 40

A historical prospective mortality study was conducted on 3579 white male workers employed between 1935 and 1976 with potential exposures to brominated compounds including 1,2-dibromo-3-chloropropane (DBCP), Tris (2,3-dibromopropyl) phosphate, polybrominated biphenyls (PBB), various organic and inorganic bromides, and DDT. The vital status as of 31 December 1976 was determined for 3384 (95%) of these workers: 2806 (79%) were still living and 578 (16%) had died. Death certificates were obtained for 541 deaths (94% of all deaths). The mortality experience of the entire cohort and several subcohorts was compared with that of United States white men adjusted for age and calendar time. The comparison statistic was the commonly used standardised mortality ratio (SMR). Historical industrial hygiene data were not available, and the workers were classified by their work areas or departments in order to estimate their potential exposures. Overall mortality for the entire cohort and several subgroups was significantly lower than expected. For the entire cohort, significant mortality deficits were observed in diseases of the circulatory system, non-malignant respiratory disease, and diseases of the digestive system. On the other hand, mortality from diabetes mellitus was significantly raised for the cohort. No significant overall or cause-specific mortality excess was detected among employees potentially exposed to either TRIS or DDT. A significant mortality excess due to diseases of the circulatory system was observed among workers potentially exposed to DBCP. Mortality from testicular cancer was significantly higher than expected among those potentially exposed to other organic bromides. The common potential exposure of those who had died of testicular cancer was methyl bromide. Owing to the lack of accurate historical exposure information and the fact that many workers were potentially exposed to a multitude of chemicals, it is difficult to draw definitive statements on the causations of the observed mortality excesses.
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PMID:Mortality of workers potentially exposed to organic and inorganic brominated chemicals, DBCP, TRIS, PBB, and DDT. 631

Body water estimates were obtained within 12 h of birth in 52 infants of non-diabetic mothers and 61 infants of diabetic mothers. Neonates were grouped as normally-grown or macrosomic. Total body water and extracellular water were estimated from antipyrine space and corrected bromide space, respectively. Intracellular water was assumed to be the difference between total and extracellular water. Infants of diabetic mothers, whether normally-grown or macrosomic, had markedly less mean total body water than normally-grown neonates of non-diabetic mothers. No effect of neonatal macrosomia or maternal diabetes on extracellular and intracellular water estimates could be detected with the techniques used. It is suggested that changes in total body water occur as a result of excessive fat accretion during fetal life.
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PMID:Maternal diabetes and neonatal macrosomia. III. Neonatal body water estimates. 664 74

Sera from patients with insulin-dependent diabetes mellitus (IDDM) containing islet cell surface antibodies (ICSA) were studied for their capacity to lyse cultured rat islet cells. The uptake of ethidium bromide was used to identify lysed cells and immunofluorescent staining with antisera to insulin, glucagon, somatostatin, or pancreatic polypeptide was used to identify the different islet cell types (B-, A-, D-, and PP-cells, respectively). Our experiments showed that in the presence of complement, sera containing ICSA lysed 81% of the B-cells, but 10% or less of the A-, D-, and PP-cells. Normal control sera resulted in lysis of less than 4% of each of the islet cell types. The demonstration that ICSA are preferentially lytic for B-cells may be important in defining the role of these autoantibodies in the pathogenesis of IDDM, particularly since the B-cell mass in diabetics is markedly reduced relative to the other islet cell types.
Diabetes 1982 May
PMID:Preferential lysis of pancreatic B-cells by islet cell surface antibodies. 675 62

We studied serum from 36 patients with insulin-dependent diabetes mellitus (IDDM) for the capacity to lyse beta cells. Immunofluorescence revealed an islet-cell cytoplasmic antibody (ICA) in 20 patients with IDDM and an islet-cell-surface antibody (ICSA) in 23. Neither ICA nor ICSA was found in any of 21 normal controls or 15 patients with non-insulin-dependent diabetes. In the presence of complement. ICSA-positive serum caused significant lysis as measured by release of 51Cr (50.1 +/- 8.8 per cent) from cultured rat islet cells, but ICSA-negative serum did not (17.7 +/- 7.3 per cent) (P < 0.001). Proof that ICSA-positive serum was lytic for beta cells was obtained by a double-fluorescence technique that identified lysed cells by their capacity to take up ethidium bromide and beta cells by their staining with fluorescein-conjugated antibody to insulin. These findings suggest that cytotoxic ICSA contributes to the pathogenesis of IDDM, but the mere presence of ICSA does not appear to be sufficient to produce diabetes; family studies showed that one fourth of the serum samples from nondiabetic first-degree relatives of diabetic probands were ICSA-positive and cytotoxic for beta cells.
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PMID:Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. 700 Dec 37

The Maillard or browning reaction between sugar and protein contributes to the increased chemical modification and cross-linking of long-lived tissue proteins in diabetes. To evaluate the role of glycation and oxidation in these reactions, we have studied the effects of oxidative and antioxidative conditions and various types of inhibitors on the reaction of glucose with rat tail tendon collagen in phosphate buffer at physiological pH and temperature. The chemical modifications of collagen that were measured included fructoselysine, the glycoxidation products N epsilon-(carboxymethyl)lysine and pentosidine and fluorescence. Collagen cross-linking was evaluated by analysis of cyanogen bromide peptides using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by changes in collagen solubilization on treatment with pepsin or sodium dodecylsulfate. Although glycation was unaffected, formation of glycoxidation products and cross-linking of collagen were inhibited by antioxidative conditions. The kinetics of formation of glycoxidation products proceeded with a short lag phase and were independent of the amount of Amadori adduct on the protein, suggesting that autoxidative degradation of glucose was a major contributor to glycoxidation and cross-linking reactions. Chelators, sulfhydryl compounds, antioxidants, and aminoguanidine also inhibited formation of glycoxidation products, generation of fluorescence, and cross-linking of collagen without significant effect on the extent of glycation of the protein. We conclude that autoxidation of glucose or Amadori compounds on protein plays a major role in the formation of glycoxidation products and cross-liking of collagen by glucose in vitro and that chelators, sulfhydryl compounds, antioxidants, and aminoguanidine act as uncouplers of glycation from subsequent glycoxidation and cross-linking reactions.
Diabetes 1994 May
PMID:Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. 816 45

Structural alterations in arterial extracellular matrix components have been suggested to play a role in the development of arterial disease among patients with diabetes mellitus. This study examines the quantity and quality of collagenous components in aortas from diabetic patients. In order to obtain data about the arterial tissue concentration of type IV and V collagen in diabetic and non-diabetic patients, aortas from 21 patients with diabetes (9 with Type 1 (insulin-dependent) diabetes and 12 with Type 2 (non-insulin-dependent) diabetes), were collected at autopsy together with aortas from groups of sex- and age-matched patients. Intima and media samples from normal and fibrous plaque areas from the individual vessels were evaluated. Pulverized, dried and defatted tissue samples were subjected to chemical solubilization with cyanogen bromide and subsequent immuno-chemical quantitation of the dissolved type IV and V collagen in an ELISA. It was found that the concentration of type IV collagen was increased in the tunica media both in plaque and non-plaque areas in the samples from the diabetic patient groups as compared to the non-diabetic groups. No consistent differences in type IV collagen concentrations were found between diabetic and non-diabetic patients in tunica intima. The type V collagen concentrations and the total collagen content were not altered in the diabetic samples. The fraction of the total collagen that was solubilized during cyanogen bromide treatment was determined, and it was found that this fraction was decreased in most tissue areas in the diabetic patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aortic collagen alterations in human diabetes mellitus. Changes in basement membrane collagen content and in the susceptibility of total collagen to cyanogen bromide solubilisation. 831 50

The reaction of the methyl ester of (R)-norcarnitine with 1-bromo-2-heptadecanone produces (+)-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide, 3, which hydrolyzes to (+)-6-(carboxylatomethyl)-2-pentadecyl-4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, HPC) upon treatment with aqueous sodium hydroxide. Single-crystal X-ray analyses have confirmed the structures of (+)-HPC and 3. (+)-HPC inhibits carnitine palmitoyltransferase (CPT-I) activity for the forward reaction (palmitoyl-CoA + carnitine-->) in intact mitochondria from rat heart and rat liver. (+)-HPC competitively (versus carnitine) inhibits CPT-I activity in both rat heart and liver mitochondria with Ki = 2.8 +/- 0.5 and 4.2 +/- 0.7 microM, respectively. As one of the strongest specific inhibitors of CPT-I, HPC is a potential therapeutic agent in myocardial ischemia and Type II diabetes.
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PMID:(+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransferase-I in intact mitochondria. 842 95

Glucose and other reducing sugars react with proteins by a nonenzymatic, post-translational modification process called nonenzymatic glycosylation or glycation. The sugar-derived carbonyl group adds to a free amine, forming a reversible adduct which over time rearranges to produce a class of products termed advanced-glycation end-products (AGEs). These remain irreversibly bound to macromolecules and can covalently crosslink proximate amino groups. The formation of AGEs on long-lived connective tissue and matrix components accounts largely for the increase in collagen crosslinking that accompanies normal ageing and which occurs at an accelerated rate in diabetes. AGEs can activate cellular receptors and initiate a variety of pathophysiological responses. They modify an appreciable fraction of circulating low-density lipoproteins preventing uptake of these particles by their high-affinity tissue receptors. Advanced glycation has also been implicated in the pathology of Alzheimer's disease. Because AGEs may form by a pathway involving reactive alpha-dicarbonyl intermediates, we investigated a potential pharmacological strategy for selectively cleaving the resultant glucose-derived protein crosslinks. We now describe a prototypic AGE crosslink 'breaker', N-phenacylthiazolium bromide (PTB), which reacts with and cleaves covalent, AGE-derived protein crosslinks. The ability of PTB to break AGE crosslinks in vivo points to the importance of an alpha-dicarbonyl intermediate in the advanced glycation pathway and offers a potential therapeutic approach for the removal of established AGE crosslinks.
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PMID:An agent cleaving glucose-derived protein crosslinks in vitro and in vivo. 871 35


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