Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:021133 (ATP)
 132,114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial protein, cytochrome-c-oxidase and mitochondrial ATPase activities, which can participate in brown adipose tissue thermogenesis, were measured in the present study in order to evaluate mitochondrial activity, oxidative capacity and ATP synthesis in dietary obese rats compared to control rats. Cafeteria-diet induced increase of cytochrome-c-oxidase and ATPase activities of 54% and 37% respectively, but mitochondrial protein content remained unchanged. Fasting induced active mitochondrial protein degradation (about 50%) only in control rats, but in both cafeteria fed and post-cafeteria obese rats fasting-induced loss of mitochondrial protein was impaired. It was concluded that cafeteria diet is able to induce specifically both the oxidative capacity and the ATP synthesis in adult rat brown adipose tissue without affecting the mitochondrial protein. Furthermore, during fasting the obese (or overweight) status 'per se' regulates the overall mitochondrial protein degradation which was impaired or inactivated in overweight dietary rats compared with controls.
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PMID:Dietary regulation of fasting-induced mitochondrial protein degradation in adult rat brown adipose tissue. 133 18

It has been postulated that platelet function plays an important role in the initiation of atherosclerosis. Currently there are no definitive data on the longer-term effects of regular physical exercise on platelet function in humans. We assessed the influence of regular moderate-intensity physical exercise (brisk walking to slow jogging) on platelet aggregation in a population-based sample of middle-aged, overweight, mildly hypertensive men in eastern Finland. In this controlled study, we evaluated the net effect of exercise on platelet aggregation by studying changes in optical density and ATP release in platelet-rich plasma. A significant inhibition of secondary platelet aggregation from 27% to 36% was observed in the men taking regular exercise. These findings give new insight into the possible protective effects of exercise against the risk of ischemic heart disease.
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PMID:Inhibition of platelet aggregability by moderate-intensity physical exercise: a randomized clinical trial in overweight men. 353 15

The membrane-bound Na/K-ATPase system is an important energy regulating system for all primate cells and is suspected to be either primary or secondary affected in different but important metabolic disorders as essential hypertension, diabetes II (mature onset diabetes) or severe overweight. Rabbit smooth muscle cells grown in culture have been incubated with different concentrations of ouabain (10(-7)-10(-4) mol/l) and potassium (4 and 6 mmol/l). In controlled series, the incorporation of 3H-thymidine (and collagen secretion) during incubation with ouabain was found to be diminished by at maximum 73% (P less than 0.01) and this was found to be reversible by changing to ouabain-free medium or partly by the addition of extra potassium. The intracellular ATP level and lactate production was diminished together with the fall in 3H-thymidine incorporation. These effects were probably not due to a non-specific toxic effect of ouabain because no difference in leakage of prelabelled 3H-thymidine from cells compared to control series was seen. We suggest that an optimal function of the membrane-bound Na/K-ATPase system is of great importance not only for intracellular energy production but also for cell proliferation and protein synthesis.
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PMID:Effects of ouabain and potassium on rabbit arterial smooth muscle cells in culture. 632 36

Hexosamines have been shown to mediate effects of hyperglycemia and so-called "glucose toxicity" in insulin-sensitive tissues. To determine the effects of hexosamines on insulin synthesis and secretion, transgenic mice were created to overexpress the rate-limiting enzyme for hexosamine synthesis, glutamine:fructose-6-phosphate amidotransferase (GFA), specifically in beta-cells. GFA activity in islets of heterozygous transgenic mice was elevated 76% compared with littermate controls. The increased GFA activity led to 1.4- and 2.1-fold increased pancreatic insulin content in 2- and 10-month-old transgenic mice, respectively (P < 0.005). Fasting insulin levels were 1.6-fold higher than in littermate controls (P < 0.05). Hyperinsulinemia was evident despite a 28% reduction in insulin mRNA levels. The fasting glucose levels in the transgenic mice equaled that of controls aged 2-4 months but exceeded that of the controls aged 6-10 months (means +/- SE 6.9 +/- 0.2 vs. 5.9 +/- 0.2 mmol/l, P < 0.001). By 8 months, the males were overweight and mildly diabetic (fasting glucose 8.8 +/- 0.5 mmol/l) despite persistent hyperinsulinemia. Insulin resistance was confirmed in both males and females using the euglycemic-hyperinsulinemic clamp technique; glucose disposal rates decreased by 48% in transgenic mice (P < 0.01). Triglyceride levels did not differ, and free fatty acid levels were lower in the transgenic animals. ATP levels were unchanged in the transgenic islets. We conclude that hexosamine biosynthesis is involved in the regulation of insulin content in beta-cells by glucose. Increased hexosamine flux in the beta-cell results in hyperinsulinemia, insulin resistance, and (in males) mild type 2 diabetes.
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PMID:Transgenic mice with increased hexosamine flux specifically targeted to beta-cells exhibit hyperinsulinemia and peripheral insulin resistance. 1096 33

This article reviews the pharmacological and clinical aspects of glimepiride, the latest second-generation sulfonylurea for treatment of Type 2 diabetes mellitus (DM). Glimepiride therapy ameliorates the relative insulin secretory deficit found in most patients with Type 2 DM. It is a direct insulin secretagogue; indirectly, it also increases insulin secretion in response to fuels such as glucose. Its action to augment insulin secretion requires binding to a high affinity sulfonylurea receptor, which results in closure of ATP-sensitive potassium channels in the beta-cells of the pancreas. The question has been raised whether insulin secretagogues by acting on vascular or myocardial potassium channels may prevent ischaemic preconditioning, a physiological adaptation that could affect the outcome of coronary heart disease, but there is evidence against this concern being applicable to glimepiride. Glimepiride's antihyperglycaemic efficacy is equal to other secretagogues. It has pharmacokinetic properties that make it less prone to cause hypoglycaemia in renal dysfunction than some other insulin secretagogues, particularly glyburide (also known as glibenclamide in Europe). Its convenient once daily dosing may enhance compliance for diabetic patients who often also require medications for other co-morbid conditions, such as hypertension, hyperlipidaemia and cardiac disease. Glimepiride is approved for monotherapy, for combination with metformin and with insulin. Clinically, its reduced risk of hypoglycaemia makes it preferable to some other insulin secretagogues when attempting to achieve recommended glycaemic control (haemoglobin A(1c) (HgbA(1c)) 7%). Using suppertime neutral protamine Hagedorn (NPH) and regular insulin with morning glimepiride in overweight diabetic patients achieves glycaemic goals more quickly than insulin alone and with lower insulin doses.
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PMID:Clinical review of glimepiride. 1133 17

The Adult Treatment Panel III (ATP III) has published criteria for diagnosing the metabolic syndrome, a cluster of closely related abnormalities related to insulin resistance that increase cardiovascular disease risk. The present analysis was performed to evaluate the ability of these criteria to identify insulin-resistant individuals. The population consisted of 443 healthy volunteers, with measurements of BMI, blood pressure, fasting plasma glucose, triglycerides, HDL cholesterol concentrations, and steady-state plasma glucose (SSPG) concentration. Insulin resistance was defined as being in the top tertile of SSPG concentrations. Of the population, 20% satisfied ATP III criteria for the metabolic syndrome. Although insulin resistance and the presence of the metabolic syndrome were significantly associated (P < 0.001), the sensitivity and positive predictive value equaled 46% (69 of 149) and 76% (69 of 91), respectively. Being overweight, with high triglycerides, low HDL cholesterol, or elevated blood pressure, most often resulted in a diagnosis of the metabolic syndrome. Thus, the ATP III criteria do not provide a sensitive approach to identifying insulin-resistant individuals. The individual components vary both in terms of their utility in making a diagnosis of the metabolic syndrome and their relationship to insulin resistance, with the obesity and lipid criteria being most useful.
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PMID:Relationship to insulin resistance of the adult treatment panel III diagnostic criteria for identification of the metabolic syndrome. 1511 86

In the recent years there has been increasing interest in the effects of oral hypoglycemic drugs on the cardiovascular system. This has arisen because of recognitions that thiazolidine-diones, peroxisome proliferators-activated receptor gamma (PPAR-gamma), may have antiatherogenic actions and that sulphonylureas are capable of closing the ATP-dependent potassium channel. PPAR-gamma agonists exert antiatherogenic action by inhibition the production of monocyte inflammatory cytokines, inhibition of expression of adhesion molecules in endothelial cells, inhibition of the proliferation of vascular smooth muscle cells and have antioxidative effects. The United Kingdom Prospective Diabetes Study (UKPDS), published in 1998, found that the use of sulphonylureas had no increase in cardiovascular mortality and that metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. Recently, the STOP-NIDDM trial has been shown that patients with impaired glucose tolerance treated with the alpha-glucosidase inhibitor acarbose had a significant reduction in the risk of cardiovascular disease. Currently, the results of the UKPDS trial are the only available clinical data on which to base the choice of treatment for type 2 diabetic patients. When a glucose-lowering oral drug is considered necessary and is not contraindicated, the firstline choice is a sulphonylurea or a glinide (repaglinide or nateglinide) for diabetics who are not overweight and metformin for those who are.
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PMID:[Cardiovascular effects of oral hypoglycemie drugs]. 1534 Jul 37

The metabolic syndrome represents the association in a single individual of a cluster of metabolic and hemodynamic factors, leading to an increased risk of type 2 diabetes and/or cardiovascular diseases. Several definitions exist (WHO, EGIR, NCEP-ATP III, AACE), but all of them include a cluster of criteria (hyper glycemia or type 2 diabetes, arterial hypertension, dyslipidemia, abdominal obesity) which increased these risks in parallel to their aggregation. The prevalence of the metabolic syndrome in industrialized countries represents 10 to 30% of the adult population, depending on the definition used and of the range of age, with a regular progression, particularly in women. Thus, it is needed to identify subjects with metabolic syndrome in the general population, and not only in overweight/obese subjects. This review, briefly presents the main definitions, as well as current data on pathophysiology, prevalence and consequences of the metabolic syndrome. Steps to diagnose it and guidance for the therapeutic management of metabolic syndrome in primary care practice are described.
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PMID:[How to manage the metabolic syndrome?]. 1595 95

This study extends earlier trials indicating that atherosclerosis risk factors are underdetected and undertreated in peripheral arterial disease (PAD) patients. Recognition and treatment of hyperlipidemia and hypertension in PAD patients is suboptimal. Diabetes appears to be detected more frequently although glycemic control is still suboptimal. The use of antiplatelet therapy is particularly underutilized. Additionally, despite the demonstrated efficacy of regular exercise in PAD patients, almost half of the study sample was sedentary. Approximately one third of the current study sample was overweight and nearly one third was obese by ATP-III guidelines. Only 31% of subjects were taking dietary measures to improve their cardiovascular health, and even fewer were physically active. To rectify suboptimal management of risk factors, there is a need for increased public awareness of PAD, reimbursement and implementation of screening programs and more aggressive treatment. Future studies are needed to examine innovative interventions for identification and management of cardiovascular risk factors in patients with PAD.
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PMID:Suboptimal intensity of risk factor modification in PAD. 1601 92

Alcohol represents an important source of energy. Despite its comparatively high energy content of 7.1 g/kcal, it is still controversial whether moderate amounts of alcohol represent a risk factor for weight gain and obesity. Epidemiologic data showed a positive, negative, or no relationship between alcohol intake and body weight. Despite the difficulty in assessing alcohol intake as well as controlling for different confounders of the energy-balance equation, the conflicting epidemiologic data can be explained in most instances. Every component of the energy-balance equation is affected by the ingestion of alcohol. Moderate amounts of alcohol enhance energy intake due to the caloric content of the alcohol as well as its appetite-enhancing effects. Alcohol-induced thermogenesis is approximately 20% in healthy nonalcoholic subjects, i.e., moderate alcohol consumers, which is higher than for other energy substrates but considerably lower than in heavy alcohol consumers. This would suggest that a major fraction of the alcohol energy represents a navailable energy source for ATP synthesis in moderate non-daily alcohol consumers. Experimental evidence from several metabolic studies showed a suppression of lipid oxidation by alcohol and thus the enhancement of a positive fat balance. The nonoxidized fat is preferentially deposited in the abdominal area. The experimental metabolic evidence suggests that the consumption of moderate amounts of alcohol has to be accounted for in the energy-balance equation and may represent a risk factor for the development of a positive energy balance and thus weight gain. In the heavy alcohol consumer and eventually also in daily moderate alcohol consumers, a larger fraction of the alcohol energy might not be an available source of energy due to the induction of the microsomal ethanol-oxidizing system (MEOS). Experimental data in combination with epidemiologic findings suggest that alcohol energy counts more in moderate nondaily alcohol consumers than in some moderate daily and all heavy consumers. Accordingly the question is not "Whether alcohol calories do count" but "How much do alcohol calories count?". There seems to be a large individual variability according to the absolute amount of alcohol consumed, the drinking frequency as well as genetic factors. Presently it can be said that alcohol calories count more in moderate nondaily consumers than in daily (heavy) consumers. Further, they count more in combination with a high-fat diet and in overweight and obese subjects.
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PMID:Is alcohol consumption a risk factor for weight gain and obesity? 1604 38


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