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 usefulness of fenfluramine (F), in association with diet therapy, was investigated in 13 obese non-insulin-dependent diabetic patients with poor diabetes control on a previous sulfonylurea regimen (SU). A double-blind crossover comparison of F and placebo (P) consisted of two 7-wk treatment periods. F was administered in stepwise increased and subsequently reduced doses, while the doses of SU were kept unchanged. There was a significant weight loss in F-treated obese subjects as compared with treatment by P. The fasting levels, and particularly the postprandial blood glucose (BG) levels, were significantly lower during F than during P administration. Serum fasting insulin and blood lactate concentrations remained unchanged during the trial. Serum triglycerides and cholesterol decreased during F administration. HDL-cholesterol and apoprotein A-I increased slightly, while apoprotein B decreased during F, but not during P administration. The effect of fenfluramine on hepatic drug metabolism was assessed by using the antipyrine test. F did not cause significant changes in antipyrine metabolism. Fenfluramine therefore seems to be useful as an adjunct to diet and SU therapy in obese non-insulin-dependent diabetic patients.
Diabetes Care
PMID:Fenfluramine therapy in non-insulin-dependent diabetic patients: effects on body weight, glucose homeostasis, serum lipoproteins, and antipyrine metabolism. 675 29

Although atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in insulin-dependent diabetics, plasma levels of high density lipoprotein (HDL) cholesterol (an independent "negative" risk factor for ASCVD) have been reported to be normal or high. To test whether alterations in HDL composition might increase potential risk of insulin-dependent diabetics to ASCVD, their major constituent apolipoproteins, A-I and A-II, were measured and compared with levels in controls. HDL cholesterol levels were slightly higher (P = NS) in diabetics than in controls. The HDL cholesterol/LDL cholesterol ratio (an inverse index of relative risk of developing ASCVD) was significantly higher in diabetic men than in controls (P less than 0.02). HDL composition differed markedly in diabetics and controls: the apolipoprotein A-I/A-II ratio was significantly higher (P less than 0.001) in both diabetic men and women (diabetic men--4.1 +/- 0.5, mean +/- SD, controls 3.6 +/- 0.4; diabetic women--4.6 +/- 0.4, controls 3.9 +/- 0.5). Subsequent analysis of plasma from four patients by analytic ultracentrifugation demonstrated a high correlation (r = 0.993, P less than 0.01) between the apolipoprotein A-I/A-II ratio and HDL2, the cholesterol-rich lighter subclass of HDL thought to be the group of particles involved in reduced risk of ASCVD. Therefore, the alteration of HDL composition in insulin-dependent diabetics appears similar to that associated with reduced risk in nondiabetics. Thus, whether a genetic or acquired abnormality, the high apolipoprotein A-I/A-II ratio in insulin-dependent diabetics does not appear to counteract their increased risk of developing ASCVD.
Diabetes 1981 Feb
PMID:High density lipoprotein composition in insulin-dependent diabetes mellitus. 678 57

Nonenzymatic glucosylation of lysine residues of high-density lipoprotein (HDL) was shown to occur in vitro. Most of the incorporated glucose was localized to apoprotein A-I, but other apoproteins were glucosylated as well. Glucosylated high-density lipoproteins (glcHDL) had enhanced electrophoretic mobility on agarose. With increasing amounts of glucose incorporated there was a proportionate increase in the rate of clearance of glcHDL when injected intravenously into guinea pigs. When 60% of lysines were derivatized, clearance of glcHDL was 60% faster than that of control HDL. When as few as 2% of lysines were glucosylated, there was still an 8% increase in the rate of clearance. Uptake of glcHDL by macrophages was not increased. The accelerated clearance of glcHDL from plasma may be relevant to the decreased HDL levels observed in diabetic subjects.
Diabetes 1982 Nov
PMID:Nonenzymatic glucosylation of high-density lipoprotein accelerates its catabolism in guinea pigs. 681 43

The effects of a high fat diet (30% (w/w) corn oil) on chronic streptozotocin-diabetic rats were investigated at the whole body level and at the enzyme level. The diet caused significant decreases in the extent of polydipsia (66% decrease), polyphagia (49%), polyuria (67%) and glycosuria (70%). The activities of selected hepatic enzymes from the glycolytic, gluconeogenic, ureogenic and lipogenic clusters were determined. The fat diet caused significant decreases (range: 47 to 54%) in the activity of the ureogenic enzymes carbamyl phosphate synthetase, ornithine transcarbamylase and arginase; had no effect on the glycolytic enzymes glucokinase, hexokinase and pyruvate kinase; partially decreased the diabetes-induced elevated activities of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (63% decrease), serine dehydratase (90%), alanine aminotransferase (31%) and aspartate aminotransferase (65%), and partially reversed the activity of one lipogenic enzyme, ATP citrate lyase.
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PMID:The effects of a high fat diet on chronic streptozotocin-diabetic rats. 692 68

Feeding a diet containing 2% cholesterol and 1% cholic acid (wt/wt) to rats made diabetic by administration of streptozotocin (45 mg/kg) produced marked hypercholesterolemia characterized by high concentrations of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) and a reduction in concentration of high density lipoproteins (HDL). The VLDL was unique in that it contained apo A-I and apo A-IV in addition to its usual complement of apoproteins: apo B, apo E, and the C apoproteins. IDL had a similar apoprotein composition. The HDL from these rats was deficient in apo E. Nondiabetic rats fed the same diet exhibited similar qualitative changes in lipoprotein concentration and composition but with lesser increases in VLDL and IDL concentrations. The altered apoprotein composition suggested that the hyperlipoproteinemia associated with cholesterol feeding in the rat is due to an inadequate rate of removal of lipoproteins of intestinal origin, and that this is greatly exacerbated by diabetes.
Diabetes 1980 Oct
PMID:Serum lipoproteins of diabetic rats fed a high cholesterol diet. 700 59

The relationship of plasma levels of high density lipoprotein (HDL) cholesterol, apolipoproteins A-I and A-II (the major apolipoproteins in HDL), low density lipoprotein (LDL) cholesterol, triglyceride, and glucose to microangiopathy was evaluated in 49 insulin-dependent diabetic subjects. Although the HDL cholesterol/LDL cholesterol ratio (a risk determinant for macroangiopathy) was lower in women with proteinuria, no other relationships between HDL cholesterol or the A apolipoproteins and renal microangiography were found. The only independent association between HDL and retinal microangiopathy was found in women, where an inverse correlation was found between the apo A-I/apo A-II ratio and the number of microaneurysms (rs = -0.561, P less than 0.05). Men showed strong relationships of glucose, triglyceride, cholesterol, and LDL cholesterol to renal microangiopathy whereas women, in general, had stronger correlations of these variables with retinal microangiopathy. Thus, several alterations in lipoprotein cholesterol distribution and HDL composition are associated with diabetic microangiopathy. In addition, differences between sexes suggest that previously undescribed hormonal factors may influence the severity of this process.
Diabetes Care
PMID:Plasma lipids and microangiopathy in insulin-dependent diabetes mellitus. 704 28

There is a significant increase in four of the urea cycle enzymes in liver from hypothyroid rats, arginase alone showed an opposite trend; these changes are reversed by physiological doses of thyroxine; hyperthyroidism results in a significant decrease in ornithine transcarbamoylase activity. The pattern of change in thyroidectomized and alloxan-diabetic rats showed marked similarities in respect to urea cycle and ornithine-metabolizing enzymes which are discussed in the light of the common feature of hypoinsulinism of diabetes and depressed response to insulin in hypothyroidism. The profile of ornithine-metabolizing enzymes is consonant with the decreased protein synthesis and turnover in hypothyroidism.
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PMID:Regulation of pathways of ornithine metabolism. Effects of thyroid hormone and diabetes on the activity of enzymes at the "ornithine crossroads' in rat liver. 721 33

One hundred and four patients with diabetes mellitus present for at least 15 years were tissue typed for HLA antigens AI and B8. Fifty six patients had severe proliferative retinopathy and 48 patients no retinopathy. The results were compared with a group of 200 normal blood donors. There was no significant difference in frequency of AI and B8 between the two groups od diabetic patients. The HLA pattern A-I B+8 was more frequently present among the group of patients with proliferative retinopathy.
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PMID:H.L.A. antigens in proliferative diabetic retinopathy. 722 7

In liver perfusion from sucrose-fed, streptozotocin-diabetic rats there was in comparison with normal animals, a decrease in very low density lipoprotein concentration in the perfusion medium (38.6 +/- 6.3 versus 64.4 +/- 8.4 microgram . g liver -1 3 h-1, p less than 0.05) and an increase in high density lipoprotein concentration (33.5 +/- 6.5 versus 14.0 +/- 1.9 microgram . g liver-1 3 h-1, p less than 0.005), which was paralleled by enhanced secretion of apoprotein A-I. The triglyceride: protein ratio was lower in very low density lipoprotein from diabetic animals (8.8 versus 13.4). Analysis of the apoprotein composition showed that diabetic very low density lipoprotein lacked arginine-rich protein (apo-E) and apo-C peptides; diabetic high density lipoprotein also lacked arginine-rich protein but contained more A-IV and apo-C-peptides. This may indicate net transfer of C peptides to high density lipoprotein from the degradation of very low density lipoprotein particles. The ratio of 3H-leucine: 14C-glucosamine incorporation was decreased in all diabetic lipoprotein classes suggesting increased glycosylation of apoproteins. These changes in particle composition may influence lipoprotein metabolism in diabetes through their effects on lipoprotein lipase and lecithin cholesterol acyl transferase activity, plasma half-life and tissue binding.
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PMID:Lipoprotein secretion by isolated perfused livers from streptozotocin-diabetic rats. 728

Arginine metabolism via nitric oxide (NO) synthase and other pathways was studied in coronary endothelial cells (EC) from the spontaneously diabetic BB rat, an animal model of human type I diabetes mellitus (IDDM). EC were prepared from insulin-treated diabetic BB (BBd) and non-diabetes-prone BB (BBn) rats. Basal NO synthesis was studied in EC cultured for 48 h in medium containing 0.4 mM L-arginine. At the end of the culture period, the medium was analyzed for nitrite and nitrate (two major end stable oxidation products of NO), and the cells were used to determine arginine uptake and metabolism and the activities of some arginine-degrading enzymes. For studies of arginine metabolism, cells were incubated at 37 degrees C for 1 h in Krebs-Henseleit bicarbonate buffer (pH 7.4) containing 1 mM L(-)[1-14C]arginine or L(-)[1-14C]ornithine. The rates of production of nitrite plus nitrate by BBd EC were only 15% of those of BBn cells. This impaired NO synthesis in BBd EC was not due to alterations in arginine uptake, NO synthase activity, or intracellular arginine concentrations but might have resulted from a limited intracellular availability of cofactors of NO synthase. In addition to the arginine-NO pathway, arginine was found to be metabolized to urea, ornithine, and, to a much lesser extent, CO2 via arginase and ornithine aminotransferase. The activities of arginase and the formation of ornithine and urea from arginine were decreased by 90% in BBd compared with BBn cells. These results, coupled with the reduced NO synthesis, indicate metabolic defects in arginine metabolism in BBd EC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired arginine metabolism and NO synthesis in coronary endothelial cells of the spontaneously diabetic BB rat. 748 63


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