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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now believed that the GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes have an important role in the development of obesity and non-insulin dependent diabetes mellitus (NIDDM). The protein encoded by daf-2 is 35% identical to the human insulin receptor, daf-7 codes a transforming growth factor-beta (TGF-beta) type signal and daf-16 can enhance superoxide dismutase (SOD) expression. EFAs and their metabolites can alter the cell membrane fluidity and enhance the expression of GLUT-4 and insulin receptors. EFAs can suppress TNF-alpha production and secretion, a mechanism that may have relevance to the role of these fatty acids in the pathogenesis of insulin resistance, obesity and NIDDM. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Based on this evidence, it is proposed that GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin interact with each other in ways which may have relevance to the development or abrogation of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.
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PMID:GLUT-4, tumor necrosis factor, essential fatty acids and daf-genes and their role in insulin resistance and non-insulin dependent diabetes mellitus. 1031 13

An increased basal plasma lactate concentration is present in many physiological and pathological conditions, including obesity and diabetes. We previously demonstrated that acute lactate infusion in rats produced a decrease in overall glucose uptake. The present study was carried out to further investigate the effect of lactate on glucose transport and utilization in skeletal muscle. In chronically catheterized rats, a 24-h sodium lactate or bicarbonate infusion was performed. To study glucose uptake in muscle, a bolus of 2-deoxy-[3H]glucose was injected in basal condition and during euglycemic-hyperinsulinemic clamp. Our results show that hyperlactatemia decreased glucose uptake in muscles (i.e., red quadriceps; P < 0.05). Moreover in red muscles, both GLUT-4 mRNA (-30% in red quadriceps and -60% in soleus; P < 0.025) and protein (-40% in red quadriceps; P < 0.05) were decreased, whereas the (E1alpha)pyruvate dehydrogenase (PDH) mRNA was increased (+40% in red quadriceps; P < 0.001) in lactate-infused animals. PDH protein was also increased (4-fold in red gastrocnemius and 2-fold in red quadriceps). These results indicate that chronic hyperlactatemia reduces glucose uptake by affecting the expression of genes involved in glucose metabolism in muscle, suggesting a role for lactate in the development of insulin resistance.
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PMID:Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while increasing (E1alpha)PDH gene expression in rat. 1032 87

In Western countries 25-35% of the population have insulin resistance syndrome characteristics. The defects most likely to explain the insulin resistance of the insulin resistance syndrome include: 1) the glucose transport system of skeletal muscle (GLUT-4) and its different signalling proteins and enzymes; 2) glucose phosphorylation by hexokinase; 3) glycogen synthase activity and 4) competition between glucose and fatty acid oxidation (glucose-fatty acid cycle). High carbohydrate/low fat diets deteriorate insulin sensitivity on the short term. However, on the long term, high fat/low carbohydrate diets have a lower satiating power, induce low leptin levels and eventually lead to higher energy consumption, obesity and more insulin resistance. Moderately high-carbohydrate (45-55% of the daily calories)/low-fat diets seem to be a good choice with regard to the prevention of diabetes and cardiovascular risk factors as far as the carbohydrates are rich in fibers. Long-term interventions with regular exercise programs show a 1/3 decrease in the appearance of overt diabetes in glucose intolerant subjects. Furthermore, diet and exercise interventions "normalise" the mortality rate of patients with impared glucose tolerance. Therefore, moderately high carbohydrate/low fat diets are most likely to prevent obesity and type 2 diabetes. Triglycerides should be monitored and, in some cases, a part of the carbohydrates could be replaced by fat rich in monounsaturated fatty acids. However, total caloric intake is of utmost importance, as weight gain is the major determinant for the onset of insulin resistance and glucose intolerance. Regular (when possible daily) exercise, decreases cardiovascular risk. With regard to insulin resistance, resistance training seems to offer some advantages over aerobic endurance activities.
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PMID:Interaction of physical activity and diet: implications for insulin-glucose dynamics. 1061 74

Recent studies examining the link between insulin resistance and the development of obesity and noninsulin-dependent diabetes mellitus are consistent with the involvement of tumor necrosis factor-alpha (TNF-alpha) as a central mediator. In insulin resistant obese mouse models, neutralization of TNF-alpha in circulation has been demonstrated to restore insulin-mediated glucose uptake. Adipose tissue has been shown to be a site for synthesis of TNF-alpha, with the degree of adiposity directly correlated with the level of synthesis. Studies conducted on obese human patients have demonstrated a correlation between levels of TNF-alpha, the extent of obesity, as well as the level of hyperinsulinemia observed. Mechanistic studies in cell culture have suggested that TNF-alpha functions to render cells insulin resistant through regulation of the synthesis of the insulin responsive glucose transporter as well as through interference with insulin signaling. This review will address these issues and additionally introduce the reader to the molecular aspects of TNF-alpha, its receptors as well as TNF-alpha-initiated signaling cascades, that are necessary to understand the function of this cytokine in the regulation of adipose tissue metabolism.
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PMID:Tumor necrosis factor-alpha-induced insulin resistance in adipocytes. 1065 15

GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes seem to play an important and essential role in the maintenance of glucose homeostasis, and in the pathobiology of obesity and non-insulin dependent diabetes mellitus (NIDDM). Daf-genes encode for proteins which are 35% identical to the human insulin receptor, a transforming growth factor-beta (TGF-beta) type signal and can also enhance the expression of superoxide dismutase (SOD). On the other hand, EFAs and their metabolites can increase the cell membrane fluidity and thus, enhance the expression of GLUT-4 and insulin receptors. In addition, EFAs can suppress TNF-alpha production and secretion and thus, are capable of reversing insulin resistance. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Hence, it is likely that there is a close interaction between GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin that may have relevance to the development of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.
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PMID:GLUT-4, tumour necrosis factor, essential fatty acids and daf-genes and their role in glucose homeostasis, insulin resistance, non-insulin dependent diabetes mellitus, and longevity. 1077 31

Prompted by our recent observations that GLUT-1 is expressed in fetal muscles, but not in adult muscle fibers, we decided to investigate whether GLUT-1 expression could be reactivated. We studied different stimuli concerning their ability to induce GLUT-1 expression in mature human skeletal muscle fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed GLUT-1. In contrast to GLUT-1, GLUT-4 was expressed in all investigated muscle fibers. Although the significance of GLUT-1 in adult human muscle fibers appears limited, GLUT-1 may be of importance for the glucose supplies in immature and regenerating muscle.
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PMID:Induction of GLUT-1 protein in adult human skeletal muscle fibers. 1105 76

Fatty acids, obesity and insulin resistance relationship are discussed. In the last decades fatty acids (FA) have been implicated in the etiology of insulin resistance. Initially, this process was related to FA inhibitory effects on glucose uptake mediated by the FA oxidation metabolites. This mechanism known as the Randle cycle has been presently discarded based on recent evidence for FA effects on glucose metabolism. Now is known that cytosolic lipid content and FA molecular structure determines higher or lower storage and oxidation capacity. Another factor is given by Tumor Necrosis Factor-alpha, which is overexpressed in animal and human obesity, producing insulin signaling and glucose uptake inhibition. This paper discuss the role played by FA and obesity on insulin resistance, mainly in relation to FA effects on glucose metabolism in the liver, muscle and adipose tissues. In the obesity condition adipose tissue releases higher levels of free FA which in turn stimulates hepatic glucose production. Adipose tissue also, increase TNF-alpha secretion impairing glucose utilization and insulin signaling. In muscle, cytosolic lipid content activate a Protein Kinase that inhibits the insulin signaling and reduce GLUT-4 translocation. The study of cellular and metabolic changes associated to weight gain and its relationship with insulin resistance etiology are encouraged.
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PMID:[Obesity and fatty acids in the etiology of insulin resistance]. 1122 45

The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.
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PMID:Effects of clenbuterol on insulin resistance in conscious obese Zucker rats. 1125 61

Plasma free fatty acids (FFA) play important physiological roles in skeletal muscle, heart, liver and pancreas. However, chronically elevated plasma FFA appear to have pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral and hepatic insulin resistance and, while the precise action in the liver remains unclear, a model to explain the role of raised FFA in the development of skeletal muscle insulin resistance has recently been put forward. Over 30 years ago, Randle proposed that FFA compete with glucose as the major energy substrate in cardiac muscle, leading to decreased glucose oxidation when FFA are elevated. Recent data indicate that high plasma FFA also have a significant role in contributing to insulin resistance. Elevated FFA and intracellular lipid appear to inhibit insulin signalling, leading to a reduction in insulin-stimulated muscle glucose transport that may be mediated by a decrease in GLUT-4 translocation. The resulting suppression of muscle glucose transport leads to reduced muscle glycogen synthesis and glycolysis. In the liver, elevated FFA may contribute to hyperglycaemia by antagonizing the effects of insulin on endogenous glucose production. FFA also affect insulin secretion, although the nature of this relationship remains a subject for debate. Finally, evidence is discussed that FFA represent a crucial link between insulin resistance and beta-cell dysfunction and, as such, a reduction in elevated plasma FFA should be an important therapeutic target in obesity and type 2 diabetes.
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PMID:Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. 1202 71

Insulin resistance of skeletal muscle glucose transport is a key defect in the development of impaired glucose tolerance and Type 2 diabetes. It is well established that both an acute bout of exercise and chronic endurance exercise training can have beneficial effects on insulin action in insulin-resistant states. This review summarizes the present state of knowledge regarding these effects in the obese Zucker rat, a widely used rodent model of obesity-associated insulin resistance, and in insulin-resistant humans with impaired glucose tolerance or Type 2 diabetes. A single bout of prolonged aerobic exercise (30-60 min at approximately 60-70% of maximal oxygen consumption) can significantly lower plasma glucose levels, owing to normal contraction-induced stimulation of GLUT-4 glucose transporter translocation and glucose transport activity in insulin-resistant skeletal muscle. However, little is currently known about the effects of acute exercise on muscle insulin signaling in the postexercise state in insulin-resistant individuals. A well-established adaptive response to exercise training in conditions of insulin resistance is improved glucose tolerance and enhanced skeletal muscle insulin sensitivity of glucose transport. This training-induced enhancement of insulin action is associated with upregulation of specific components of the glucose transport system in insulin-resistant muscle and includes increased protein expression of GLUT-4 and insulin receptor substrate-1. It is clear that further investigations are needed to further elucidate the specific molecular mechanisms underlying the beneficial effects of acute exercise and exercise training on the glucose transport system in insulin-resistant mammalian skeletal muscle.
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PMID:Invited review: Effects of acute exercise and exercise training on insulin resistance. 1213 93


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