Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Nicotinamide has been given both before and after clinical onset of Type 1 (insulin-dependent) diabetes mellitus in an attempt to prolong beta-cell survival. Nicotinic acid, structurally similar to nicotinamide, induces insulin resistance and increases insulin secretion in healthy individuals. It is not known if nicotinamide has similar effects. Since insulin secretion, as measured by the acute insulin response to intravenous glucose, is used to predict diabetes and to monitor therapy, the effects of nicotinamide must be established before trials in individuals at high risk of progression to Type 1 diabetes can be interpreted. Intravenous tolerance tests were performed according to the ICARUS standard protocol in 10 healthy, adult subjects (age 32 +/- 5.7 years) before and after 14 days of treatment with nicotinamide 25 mg.kg-1.day-1. The acute insulin response after nicotinamide did not differ from the control study, whether measured as the incremental 0-10 min insulin area (278 +/- 142 vs 298 +/- 130 mU.l-1.10 min-1) or as the 1 +/- 3 min insulin level (78 +/- 39 vs 81 +/- 44 mU/l). The late insulin response was equally unaffected, as were basal insulin (5.2 +/- 1.6 vs 5.6 +/- 2.1 mU/l) and glucose (5.0 +/- 0.4 vs 4.9 +/- 0.2 mmol/l) levels and glucose disposal rates (1.98 +/- 0.88 vs 2.04 +/- 0.68%/min). Nicotinamide does not affect insulin secretion and glucose kinetics in normal subjects, confirming its suitability for trials designed to delay or prevent the onset of Type 1 diabetes.
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PMID:Nicotinamide and insulin secretion in normal subjects. 835 86

Hypertension and diabetes appear to increase coronary heart disease risk in part by causing an abnormality in lipid metabolism. Most affected are patients with familial dyslipidemic hypertension (FDH) and noninsulin-dependent diabetes mellitus (NIDDM). The lipid disorders most often encountered in these patients are increased levels of triglycerides, very low-density lipoprotein (VLDL) cholesterol, and small, dense low-density lipoprotein (LDL) cholesterol, and low levels of high-density lipoprotein (HDL) cholesterol. These abnormalities appear to result from increased hepatic secretion of VLDL particles due to increased concentrations of free fatty acids and glucose, reduced VLDL clearance due to reduced activity of lipoprotein lipase, and reduced LDL clearance due to glycosylation of ligand proteins. Treatment of the dyslipidemia associated with FDH should follow the guidelines from the National Cholesterol Education Program. Treatment in men and women with NIDDM should be considered when LDL cholesterol levels are 130 mg/dl or above, triglyceride levels are 200 mg/dl or above, or non-HDL cholesterol levels are 160 mg/dl or greater. Aggressive lifestyle changes should be initiated first, including weight loss in obese patients, control of glucose levels in those with NIDDM, avoidance of antihypertensive drugs that may worsen lipid levels in patients with FDH, and eating a diet restricting saturated fat and cholesterol. Addition of lipid-altering drugs should be considered if such changes do not achieve effective lipid control. The agent should be tailored to the patient's lipid profile, in general by using bile acid resins, niacin, or reductase inhibitors to lower LDL cholesterol and gemfibrozil or niacin to lower triglycerides. Niacin should be avoided in patients with NIDDM.
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PMID:Understanding and treating dyslipidemia associated with noninsulin-dependent diabetes mellitus and hypertension. 836 60

The short-term administration of a nicotinic acid analogue (acipimox) increases insulin sensitivity and consequently glucose disposal, both in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in patients with cirrhosis. This effect has been attributed to a decrease in plasma nonesterified fatty acid (NEFA) levels and fatty acid oxidation rates, and a corresponding increase in carbohydrate oxidation. The aim of the present study was to determine whether acipimox influenced glucose disposal independent of changes in lipid metabolism. Seven normal men (age, 31 +/- 4 years; body mass index, 23.2 +/- 1.8 kg.m-2; fat-free mass [FFM], 66.8 +/- 4.2 kg) were studied on two separate occasions with hyperinsulinemic (0.06 U.kg FFM-1.h-1) euglycemic clamps (duration, 150 minutes). A primed (150 U), continuous (0.4 U.kg-1.min-1) infusion of heparin together with 10% intralipid (25 mL.h-1) was infused in both studies from -90 to 150 minutes to maintain comparable levels of plasma NEFA and lipid oxidation rates. Acipimox (500-mg capsules) or placebo were administered orally in a double-blind random fashion at t = -90 and t = 0 minutes. Whole-body lipid and carbohydrate oxidation were measured in the last 30 minutes of both the basal (preclamp) period (-30 to 0 minutes) and the clamp period (120 to 150 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate. 848 48

Plasma nonesterified fatty acid (NEFA) levels are increased in the insulin-stimulated state in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to the decrease in peripheral and hepatic insulin sensitivity. To test this hypothesis and to avoid the confounding effect of obesity, we examined the effect of decreasing plasma NEFA levels on peripheral and total glucose metabolism in eight non-obese, NIDDM patients. Each received 250 mg Acipimox (a nicotinic acid analogue) or placebo at 0 and 120 minutes on separate occasions. [6,6-2H2]-glucose (0 to 300 minutes) and insulin (120 to 300 minutes) were infused in each study, and isoglycemia was maintained. Plasma NEFA levels (140 +/- 30 v 600 +/- 70 mumol/L [SEM]; P < .001) and forearm NEFA uptake measured with [1-14C]-palmitate (+93 +/- 21 v +313 +/- 42 nmol x 100 mL forearm-1; P < .001) were decreased with acipimox during the basal period (90 to 120 minutes), with no change in forearm glucose uptake (+334 +/- 80 and +330 +/- 60 nmol x 100 mL forearm-1 x min-1) and hepatic glucose output ([HGO] 13.6 +/- 0.9 and 13.4 +/- 0.7 mumol.kg-1 x min-1). Serum insulin (256 +/- 12 and 266 +/- 18 pmol/L) and plasma glucose (9.5 +/- 0.6 and 9.4 +/- 0.5 mmol/L) levels were comparable during the clamp period (270 to 300 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral and hepatic insulin sensitivity in non-insulin-dependent diabetes mellitus: effect of nonesterified fatty acids. 849 15

Acanthosis nigricans is a reaction pattern to over a dozen different causes. The skin, most classic in the axilla, is dark, soft, velvet-like with fine folding and papillae. The mechanism of this skin change is decreased viscosity of extracellular matrix (ECM) combined with mechanical extrusion of ECM into papillae extending out from the upper dermis. It occurs in obesity (increased mechanical pressure on ECM), diabetes (decreased quality of glycosaminoglycans) (GAG), excess corticosteroids (decreased quality of GAG), pineal tumors (increased ECM and edema), other endocrine disorders (alterations in the quality of GAG), multiple genetic variants (structural and chemical change), from drugs such as nicotinic acid, estrogens, corticosteroids (weakened or altered GAG) and adenocarcinoma (fractions of depolymerized or altered GAG released from the tumor area are incorporated into and weaken the skin GAG). Acanthosis nigricans was first reported in 1890 as a cutaneous sign of internal malignancy. Acanthosis nigricans presents an opportunity to better understand what is occurring in the ECM in many disorders. The understanding of the association of AN and internal malignancy will expand our understanding of how a neoplasm decreases generalized ECM viscosity.
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PMID:Acanthosis nigricans--decreased extracellular matrix viscosity: cancer, obesity, diabetes, corticosteroids, somatotrophin. 850 93

Niacin has been used for many years to treat hyperlipidemia. It has been shown to reduce coronary death and non-fatal myocardial infarction and, in a separate analysis of long-term (15-year) follow-up, all cause mortality. It reduces total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides and increases high density lipoprotein cholesterol (HDL-C). Sustained-release niacin may be associated with more dramatic changes in LDL-C and triglyceride, whereas the short acting preparation causes greater increases in HDL-C. The increase of HDL-C occurs at a lower dose (1500 mg/day) than the reduction of LDL-C (> 1500 mg/day). Niacin also favorably influences other lipid parameters including lipoprotein(a) [Lp(a)], alimentary lipemia, familial defective apolipoprotein B-100 and small dense LDL. Combination of niacin with a bile acid sequestrant or a reductase inhibitor represents a powerful lipid-altering regimen. Whereas the reductase inhibitors and bile acid binding resins primarily affect LDL-C, the combined therapy has a synergistic effect to reduce LDL-C and, in addition, the niacin reduces triglycerides and increases HDL-C. The major drawback in the use of niacin is associated side effects (flushing and palpitations) and toxicity (worsening of diabetes control, exacerbation of peptic ulcer disease, gout, hepatitis). Niacin has a long history of use as a lipid lowering agent and has several attractive features. Unfortunately, the side effect profile of this agent warrants its use only in patients with marked dyslipidemia in whom side effects and potential toxicity are closely monitored.
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PMID:New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. 885 85

The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) complex. The recently cloned catalytic unit of this complex has been shown to be regulated by insulin, dexamethasone, cAMP, and glucose. Using a combination of intralipid and/or nicotinic acid infusions and a pancreatic clamp technique, we maintained plasma free fatty acids (FFAs) at three different levels (0.26 +/- 0.07, 0.56 +/- 0.09, and 1.59 +/- 0.12 mmol/l) in the presence of well-controlled hormonal and metabolic conditions. An increase in the plasma FFA concentration within the physiological range caused a rapid, greater than threefold increase in the mRNA and protein levels of the catalytic subunit of Glc-6-Pase in the liver. These data indicate that the in vivo gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein.
Diabetes 1997 Jan
PMID:Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. 897 Oct 97

A hypothesis is advanced, according to which substances containing an amino group can compete with glucose in binding with protein groups and inhibiting in this way glycosylation. Screening in vitro experiments with nicotinic acid, nicotinamide, piracetam, panangin, ascorbic acid, bucarban, betanase, and adebit in a concentration of 10(-3) M were performed. Bucarban, betanase, and adebit were found to be capable of inhibiting glycosylation. Daily oral administration of bucarban and adebit in therapeutic doses for one month reduced the blood fructosamine level in rats with alloxan diabetes without changing the level of glycemia.
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PMID:[The pharmacological blockade of protein glycosylation in diabetes mellitus using sulfonylurea derivatives and biguanides]. 902 9

The effects of daily supplemental chromium (200 micrograms) complexed with 1.8 mg nicotinic acid on plasma glucose and lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, were assessed in 14 healthy adults and 5 adults with noninsulin-dependent diabetes mellitus (NIDDM) using a double-blind crossover study with 8-wk experimental periods. Eight of the 14 healthy subjects and all 5 subjects with NIDDM also underwent an oral glucose tolerance test with assessment of 90 min postprandial plasma glucose and insulin concentrations. No statistically significant effects of chromium nicotinic acid supplementation were found on plasma insulin, glucose, or lipid concentrations, although chromium nicotinic acid supplementation slightly lowered fasting plasma total and LDL cholesterol, triglycerides, and glucose concentrations, and 90-min postprandial glucose concentrations in individuals with NIDDM.
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PMID:Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors. 909 56

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with approximately two fold increase in coronary heart disease (CHD) in men and fourfold increase in CHD in women. In most studies, the duration of diabetes and severity of glycemia are only weakly related to CHD in NIDDM, suggesting that the prediabetic period may be important for the increased CHD in NIDDM subjects. Both hyperinsulinemia and/or insulin resistance predict the development of NIDDM. A number of studies have shown that increased cardiovascular risk factors (especially high triglyceride, blood pressure, and small dense low-density lipoprotein (LDL) and low high-density liproprotein (HDL) cholesterol) precede the onset of NIDDM. Recent data from the San Antonio Heart Study suggest that the atherogenic pattern of cardiovascular risk factors is more marked in prediabetic women than in prediabetic men, thus partially explaining the higher risk of CHD in prediabetic women than in prediabetic men. The atherogenic changes in cardiovascular risk factors appear to be mainly due to increased hyperinsulinemia and insulin resistance in nondiabetic subjects. Interventions to reduce cardiovascular disease in NIDDM subjects should emphasize the primary prevention of NIDDM and very aggressive treatment of traditional cardiovascular risk factors in prediabetic subjects. Treatment of hypertension and dyslipidemia in high-risk patients for NIDDM should avoid agents that further worsen insulin resistance (nicotinic acid, beta blockers, and thiazides), as subjects with hypertension and dyslipidemia are already at increased risk of NIDDM.
J Diabetes Complications
PMID:The prediabetic problem: development of non-insulin-dependent diabetes mellitus and related abnormalities. 910 90


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