C. N. Hales

Bio: C. N. Hales is an academic researcher from University of Cambridge. The author has contributed to research in topics: Diabetes mellitus & Carbohydrate metabolism. The author has an hindex of 4, co-authored 5 publications receiving 5420 citations.

The glucose fatty acid cycle in obesity and maturity onset diabetes mellitus

Abstract: The present account contains a brief summary of the concept of the glucose fatty acid cycle and of the experimental evidence on which it is based and of its possible importance in the interpretation of metabolic disturbances in obesity and maturity onset diabetes. Much of the experimental evidence on which the concept is based has been published in detail elsewhere.' ' The concept of the glucose fatty acid cycle is concerned with a reciprocal relationship between the metabolism of glucose and of fatty acids in muscle and adipose tissue. It is based upon the inhibitory effects of glucose and insulin on the release of fatty acids from glycerides in the two tissues and upon the inhibitory effects of fatty acid oxidation on the metabolism of glucose by glycolysis and oxidation in muscle and the action of insulin thereon. Adipose tissue may contribute to the oxidation of fatty acids in muscle because of its role as a source of plasma non-esterified fatty acids (NEFA). In normal animals the functioning of the cycle leads to the release and oxidation of fatty acids and to suppression of glucose oxidation during periods of carbohydrate deprivation. After intake of carbohydrate the release and oxidation of fatty acids is promptly suppressed and the uptake and oxidation of glucose is facilitated. The release of insulin from pancreatic 0 cells which is stimulated by glucose is an important factor in these changes. In alloxan-diabetes in the rat the cycle is disturbed in such a way that fatty acids continue to be oxidised in muscle a t an accelerated rate for some time after the provision of glucose and insulin. This accelerated rate of fatty acid oxidation leads to impaired uptake, glycolysis and oxidation of glucose in the presence of insulin and it appears to be an important factor in the insulin insensitivity or antagonism exhibited by muscles of diabetic rats. The most direct evidence for the glucose fatty acid cycle and for the view that many disturbances of glucose metabolism in muscle in diabetes are secondary manifestations of accelerated release and oxidation of fatty acids have been obtained in in vitrv experiments with rat muscle. These are summarised in the following section. Possible extensions of the cycle to liver where increased rates of fatty acid oxidation may accelerate gluconeogenesis are also briefly considered. In maturity onset diabetes and in established obesity there is evidence that the cycle is disturbed in such a way that fatty acids may be released and oxidised a t an accelerated rate in spite of the presence of adequate amounts of circulating glucose and insulin. This has raised the possi-

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

Cardiovascular Morbidity and Mortality Associated With the Metabolic Syndrome

Abstract: OBJECTIVE —To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization (WHO) RESEARCH DESIGN AND METHODS —A total of 4,483 subjects aged 35–70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome In subjects who had type 2 diabetes ( n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) ( n = 798), or insulin-resistance with normal glucose tolerance (NGT) ( n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 69 years RESULTS —In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome ( P P P = 0002) CONCLUSIONS —The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from different studies

Mechanisms linking obesity to insulin resistance and type 2 diabetes

Abstract: Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention

Subcutaneous and visceral adipose tissue : Their relation to the metabolic syndrome

Abstract: Methods for assessment, e.g., anthropometric indicators and imaging techniques, of several phenotypes of human obesity, with special reference to abdominal fat content, have been evaluated. The correlation of fat distribution with age, gender, total body fat, energy balance, adipose tissue lipoprotein lipase and lipolytic activity, adipose tissue receptors, and genetic characteristics are discussed. Several secreted or expressed factors in the adipocyte are evaluated in the context of fat tissue localization. The body fat distribution and the metabolic profile in nonobese and obese individuals is discussed relative to lipolysis, antilypolysis and lipogenesis, insulin sensitivity, and glucose, lipid, and protein metabolism. Finally, the endocrine regulation of abdominal visceral fat in comparison with the adipose tissue localized in other areas is presented.