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)

To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.
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PMID:Inhibition of nitric oxide synthase by NG-nitro-L-arginine causes a preferential decrease in pancreatic islet blood flow in normal rats and spontaneously diabetic GK rats. 752 Aug 63

The effects of fluvastatin treatment on lipid profile and apolipoproteins were assessed in a group of 31 Chinese patients with hypercholesterolemia, maintained on a constant low-fat diet. Some patients had the additional cardiovascular risk factors of hypertension and non-insulin-dependent diabetes mellitus, and 6 patients had familial hypercholesterolemia. Baseline lipid levels were measured after a 4-week placebo period, and these were repeated after 4 weeks of treatment with fluvastatin 20 mg daily, and after 4 weeks of treatment with fluvastatin 40 mg daily. Total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B were each reduced to the same extent with the 2 doses of fluvastatin (-20%, -26%, and -20%, respectively). Triglycerides and very low density lipoprotein cholesterol were also reduced by about 12% with the 2 doses of fluvastatin. Apo A-I was increased by 7% and high density lipoprotein cholesterol (HDL-C) was increased by 10% with the 40 mg dose. The increase in HDL-C was due to increases in both HDL2-C (18%) and HDL3-C (7%). Lipoprotein(a) levels did not show any significant change with the 2 doses of fluvastatin in this short-term study. One patient developed reversible asymptomatic elevation of liver enzymes with the higher dose of fluvastatin; otherwise the drug was well tolerated and no patients had to be withdrawn from the study.
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PMID:Effects of fluvastatin on lipid profile and apolipoproteins in Chinese patients with hypercholesterolemia. 760 89

Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG-CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG+CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG+CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very-low-density lipoprotein (VLDL)+chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios (P < .04) in the HTG+CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters [CE]) in all of the lipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG-CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG+CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PL to apo A-I ratios in both controls and HTG-CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG+CVD group. The HTG-CVD group also had a significantly greater increase in the VLDL+CM PL to apo B ratio (P = .038) at 3 hours than the HTG+CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PL to apo A-I ratio seen in HTG+CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG+CVD patients was a failure to increase the PL content per particle in VLDL+CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.
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PMID:Postprandial lipoprotein responses in hypertriglyceridemic subjects with and without cardiovascular disease. 763 51

Quantitative and qualitative modifications of plasma apolipoproteins could provide additional information in predicting coronary heart disease (CHD) in non-insulin-dependent diabetes mellitus (NIDDM). We examined 17 men and 15 women aged over 65 years affected by NIDDM. Alcohol intake, smoking habits, antidiabetic therapy, body weight, stature, and body mass index were considered. Furthermore, serum lipids and apolipoprotein A-I and B levels were determined. Apo A-I was characterized by isoelectric focusing (IEF) and immunoblotting. The men were heavier and taller than the women. The women had significantly higher serum levels of total cholesterol, HDL-cholesterol, and apo A-I than the men. The levels of HDL-cholesterol, apo A-I and B were significantly influenced by an interaction between sex and the duration of diabetes. An invariant pattern was observed for apo A-I isoforms in samples from diabetic subjects of both sexes. The percentage distribution of serum apo A-I isoforms determined by densitometry is quite different from that previously reported in the literature for the general population. Quantitative modification in apo A-I isoforms could be due to the specific pathology and these variations could partly explain reduced levels of HDL-cholesterol in diabetic patients.
Diabetes Res 1994
PMID:Analysis of serum apolipoprotein A-I in elderly non-insulin-dependent diabetic patients. 764 90

The clinical characteristics of subjects with a missense glucokinase mutation, gly299-->arg, were studied in a large pedigree, BX, initially characterized by some members having Maturity Onset Diabetes of the Young (MODY). Glucose tolerance, beta cell function and insulin sensitivity were measured with Homeostasis Model Assessment (HOMA) and with a 'Continuous Infusion of Glucose with Model Assessment' (CIGMA) test. Diabetic complications were clinically assessed. Subjects with glucokinase gly299-->arg were the same age, height, and obesity as the subjects without the mutation. Diabetes was usually asymptomatic at diagnosis and was treated with diet alone in 15 of the 18 subjects. Five of the 11 adult females had been diagnosed when they developed gestational diabetes. The fasting plasma glucose concentrations at the time of study were 4.3-12.6 mmol l-1, with the higher levels being in the more obese (p < 0.05) and in the older subjects (p < 0.05). In subjects with the mutation, beta cell function was impaired, being geometric mean 63% (normal-100%) compared with 126% in the subjects without the mutation (p < 0.001) measured by HOMA and in a subset assessed by CIGMA 59% and 127% (p < 0.01), respectively. There was no difference in fasting insulin concentrations, insulin sensitivity, lipid concentrations or blood pressure between the groups. The haemoglobin A1c was raised (mean 6.5% compared with 5.5% in the subjects without the mutation), but microvascular and macrovascular complications were uncommon. The subjects with the mutation did not have microalbuminuria but had an impaired vibration perception threshold compared with subjects without the mutation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical characteristics of subjects with a missense mutation in glucokinase. 775 56

We investigated the association between hyperinsulinemia and changes in lipid, lipoprotein, and apolipoprotein that would increase the risk of coronary artery disease (CAD) independent of glucose tolerance. A coronary angiogram was recorded in 127 male subjects, including 41 with normal glucose tolerance, 41 with impaired glucose tolerance, and 45 with non-insulin-dependent diabetes mellitus (NIDDM). Subjects were divided into 2 groups according to results: the group with CAD (n = 94) and the group with normal coronary arteries (n = 33). All subjects were normolipidemic (total cholesterol < 230 mg/dl and triglycerides < 150 mg/dl). The CAD group had a significantly lower plasma level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) and a higher level of apolipoprotein B (apo B) than the normal group with normal glucose tolerance. In considering subjects with impaired glucose tolerance or NIDDM, the CAD group had a significantly lower plasma level of HDL cholesterol and apo A-I and a significantly higher plasma level of total cholesterol, triglycerides, and apo B than the normal group. In each of the subjects with normal and impaired glucose tolerance, and NIDDM, the elevation of plasma insulin concentration during both the complete test period and the early phase of an oral glucose challenge was significantly higher in the CAD than in the normal group. In all subjects, graded reductions in HDL cholesterol and apo A-I and graded increases in plasma total cholesterol, triglycerides, and apo B were observed with increasing tertiles of the postglucose challenge measurements of insulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation of angiographically defined coronary artery disease and plasma concentrations of insulin, lipid, and apolipoprotein in normolipidemic subjects with varying degrees of glucose tolerance. 781 Apr 85

The term lipoprotein Z (remnant-like particles) refers to lipoproteins that do not have an immunoaffinity to gel mixture of anti-apo A-I and apo B100 monoclonal antibodies (JI-H antibody). Lp Z is enriched in apo E and cholesterol esters. Quantification of this lipoprotein provides a useful index of atherogenic chyromicron and VLDL remnant particles. Serum concentration of this lipoprotein is well correlated to serum triglycerides in normal subjects and patients with hypertriglyceridemia, and to serum LDL-cholesterol in normal subjects. The normal range of this lipoprotein is below 5 mg/dl and the increased serum concentration is often observed in ischemic heart disease, diabetes mellitus, hypertriglyceridemia and fatty liver.
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PMID:[Lipoprotein Z]. 785 93

Long-standing risk factors for the development of coronary artery disease (CAD) have typically included age, blood levels of total and high-density lipoprotein (HDL) cholesterol, blood pressure, cigarette use, diabetes mellitus, and left ventricular hypertrophy on electrocardiography. Each of the traditional risk-factor measures has expanded in scope over time; for instance, systolic and diastolic blood pressure levels are each associated with the occurrence of CAD, and an individual need not be hypertensive to be at an increased risk. Although total (or low-density lipoprotein cholesterol) and HDL cholesterol are highly associated with CAD incidence, other newer lipid measures such as apolipoproteins A-I and B, and genetic markers have shown little or no additional effect in predicting CAD. Diabetes mellitus has been consistently associated with CAD but less data are available to demonstrate independent roles for obesity and regional adiposity. Although reports are more recent, hematologic factors such as fibrinogen concentration and leukocyte count have been consistently associated with CAD in observational studies. Prediction equations continue to emphasize the traditional biological factors and not behaviors. Among life-style habits such as diet, sedentary activity, and cigarette smoking, only the latter has been consistently used in CAD prediction because of its independent effect.
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PMID:Established risk factors and coronary artery disease: the Framingham Study. 794 84

The aim of the present study was to determine if low-density lipoproteins (LDLs) and red blood cell (RBC) membranes from diabetic patients present an increased susceptibility to lipoperoxidation, which might be related to the increased incidence of atherosclerosis in diabetes. LDLs and RBC membranes were isolated from 11 insulin-dependent (IDDM) and 18 non-insulin-dependent diabetic (NIDDM) patients and exposed to a peroxidative stress by incubation with phenylhydrazine. The susceptibility to peroxidation was determined by measuring the production of thiobarbituric acid-reactive substances (TBARS) after the incubation. The following parameters were also evaluated: plasma glucose, triglycerides (TG), phospholipids (PL), total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A-I, apo B, hemoglobin A1c (HbA1c), LDL PL and cholesterol, LDL fatty acid composition, and RBC membrane PL and cholesterol. Although they were apparently normolipidemic, diabetic patients showed an increased susceptibility to peroxidation in LDLs and erythrocyte membranes as compared with control subjects. The amount of arachidonic acid in LDLs and the PL concentration of RBC membranes from diabetic patients were significantly higher than in normal subjects. The increased lipoperoxidability of both RBC membranes and LDLs might play a central role in the pathogenesis of the vascular complications of diabetes mellitus.
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PMID:Increased susceptibility to lipid oxidation of low-density lipoproteins and erythrocyte membranes from diabetic patients. 799 Jun 98

High-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A-I, and apo A-II levels were measured in 1,219 normal subjects with no clinical evidence of coronary artery disease, 81 subjects without diabetes but with "significant" coronary artery disease determined by coronary arteriography, and 151 subjects with non-insulin-dependent diabetes mellitus (48 with clinical coronary artery disease and 103 without such disease). In the normal subjects, apo A-II levels were less influenced by age, gender, and use of medications than were apo A-I or HDL-C levels. HDL-C, apo A-I, and apo A-II levels were significantly lower in subjects who had coronary artery disease with or without diabetes than in control subjects. After adjustments were made for age and sex, however, apo A-II levels were no longer significantly different between subjects with diabetes who had and those who did not have coronary artery disease. In subjects without diabetes, apo A-II may provide some advantages over apo A-I and HDL-C in the assessment of risk of coronary artery disease because it is influenced less by age, gender, and medications. In subjects with diabetes, however, apo A-II levels are similar in the presence or absence of coronary artery disease.
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PMID:Apolipoprotein A-II levels and coronary artery disease in subjects with and without diabetes: a study with use of a specific radioimmunoassay for apolipoprotein A-II. 849 40


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