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)

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

A 34-year-old male with a history of angina pectoris suddenly developed weakness in the right upper and lower limbs, and consulted our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) suggested cerebral infarction. Cerebral angiography revealed stenosis at the M1 portion of the left middle cerebral artery. Hypertension, diabetes, tobacco or hyperlipidemia were not considered as risk factors for cerebral infarction. The lipoprotein (a) [Lp(a)] level was high. In the present case, medication with a nicotinic acid agent, niceritrol, for hyperlipoproteinemia and low density lipoprotein (LDL) apheresis were performed. Concerning family history, the patient's mother and younger sister had hyperlipoproteinemia. Recent studies have reported that increased Lp(a) levels are an independent risk factor even in cerebral infarction and coronary artery disease. Measurement of Lp(a) levels and treatment for increased Lp (a) levels may be important.
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PMID:[Juvenile cerebral infarction with familial hyperlipoproteinemia (a)--case report]. 916 61

Islet amyloid polypeptide forms islet amyloid deposits in non-insulin-dependent diabetes mellitus. We have generated transgenic mice which express human islet amyloid polypeptide in their pancreatic beta cells yet do not develop islet amyloid deposits despite producing levels of the amyloidogenic human peptide 2 - 3 fold higher than the native (mouse) peptide. To determine whether marked overproduction of islet amyloid polypeptide is a potential cause of islet amyloid formation, we increased expression of this transgene by producing homozygous transgenic animals and by making heterozygous mice experimentally insulin resistant with nicotinic acid. Pancreatic content of islet amyloid polypeptide-like immunoreactivity in homozygous and nicotinic acid-treated mice was 2-fold (25 +/- 7 fmol/microg; n = 6) and 3.5-fold (47 +/- 20 fmol/microg; n = 3) higher, respectively, than that of untreated heterozygous animals (13+/-2 fmol/microg; n = 11; both p < 0.05). Despite this marked increase in production of islet amyloid polypeptide, neither group of mice developed gross islet amyloid deposits even after 16 months of age. We conclude that overproduction of islet amyloid polypeptide, even as produced by extreme insulin resistance, is not in itself sufficient for islet amyloid formation.
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PMID:Transgenic overproduction of islet amyloid polypeptide (amylin) is not sufficient for islet amyloid formation. 923 Mar 54

The aim was to examine the feasibility and efficacy of a multifactorial risk factor intervention program in hypertensive patients at high cardiovascular risk. Treated hypertensive men, aged 50 to 72 years, with at least one of the following: serum cholesterol concentration > or = 6.5 mmol/L, diabetes mellitus, or smoking were randomized to multifactorial risk factor intervention (n = 253) or usual care (n = 255). The specific intervention was based on group meetings to encourage a lipid lowering diet and smoking cessation. Cholestyramine, nicotinic acid, fibrates, and later statins were used either as single drug therapy or in combination, following agreed guidelines in patients in whom the nonpharmacological intervention was judged to be insufficient. Usual care was given according to clinical practice. The median follow-up time was 6.6 years. Sixty-four patients (25.1%) died in the usual care group, compared with 41 patients (16.2%) in the intervention group (P = .016; 95% confidence interval, relative risk 0.42 to 0.92). The overall risk for fatal and nonfatal cardiovascular events was 29% lower in the intervention group than in the usual care group (P = .041). Relative to usual care, the intervention program lowered mean in-trial serum concentrations of total cholesterol (6.3%, P < .0001), LDL cholesterol (9.1%, P < .0001), and blood glucose (0.2 mmol/L, P < .05). Among smokers, at entry, cotinine-adjusted quit rates were 28% in the intervention group and 11% in the usual care group (P = .012) after 3 years. This study illustrates the very high cardiovascular risk in hypertensive patients 50 to 72 years of age with additional risk factors. The results indicate, however, that the gloomy prognosis may be improved by a dedicated risk factor intervention program.
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PMID:Mortality rates in treated hypertensive men with additional risk factors are high but can be reduced: a randomized intervention study. 950 45

Patients with diabetes mellitus have an increased risk for coronary artery disease due to hyperglycemia, hypertension, dyslipidemia, and other risk factors. The diabetic dyslipidemia in these patients is characterized by moderately high levels of (1) serum cholesterol and triglycerides; (2) small, dense low-density lipoprotein (LDL) particles; and (3) low high-density lipoprotein (HDL) cho-lesterol concentrations. Recent clinical trials have demonstrated the benefits of cholesterol-lowering therapy in both diabetic and nondiabetic patients, thus supporting aggressive treatment of diabetic dyslipidemia for coronary artery disease prevention. A 3-step approach is recommended for the treatment of diabetic dyslipidemia. First, modification of diet and lifestyle, including decreased intakes of cholesterol, cholesterol-raising fats, and total energy, and increased physical activity should be advised. Second, good glycemic control should be achieved with diet and hypoglycemic drugs, if needed. Third, lipid-lowering drugs should be used, if necessary. Non-HDL cholesterol levels, which include both very-low-density lipoprotein (VLDL) and LDL cholesterol, should be the target of cholesterol-lowering therapy. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (the "statins") has become the first-line drug therapy for diabetic dyslipidemia. Bile acid sequestrants are effective cholesterol-lowering agents in normotriglyceridemic patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients with severe hypertriglyceridemia may require fibric acids or n-3 polyunsaturated fatty acids. Nicotinic acid worsens hyperglycemia; therefore, it should be avoided in most cases. The efficacy and safety of estrogen-replacement therapy in postmenopausal women with diabetes needs to be determined. The combination of two lipid-lowering agents may be appropriate for some NIDDM patients but should be used judiciously.
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PMID:Treatment of diabetic dyslipidemia. 952 14

Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
Diabetes Care 1998 Jan
PMID:Management of dyslipidemia in adults with diabetes. 953 88

The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min x 4 h) in type 2 diabetic patients and in normal volunteers. Lowering of FFAs (from approximately 600 to approximately 100 micromol/l) lowered ISRs in type 2 diabetic patients during isoglycemic clamping (from 139 to 101 pmol/min; -23%; P < 0.02) and euglycemic clamping (from 99 to 63 pmol/min; -36%; P < 0.03) and in normal subjects during euglycemic clamping (from 127 to 96 pmol/min; -25%; P < 0.03). In addition, peripheral insulin concentrations decreased by approximately 30% in diabetic and nondiabetic subjects. NA had no direct effect on ISRs; that is, NA did not change ISRs when plasma FFAs were prevented from decreasing with a lipid/heparin infusion. We concluded that 1) basal plasma FFAs exerted physiologically important, long-lasting effects supporting 25-33% of basal insulin secretion in nondiabetic and diabetic subjects; 2) basal plasma FFAs were responsible for some of the hyperinsulinemia in normoglycemic obese subjects; and 3) NA had no direct effect on insulin secretion.
Diabetes 1998 Oct
PMID:Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects. 975 99


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