bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Adipocyte in Type 2 Diabetes
Authors: Farmer Stephen R. , Prusty Deepanwita 
Published: August 2003

Abstract

Obesity is a major risk factor for several pathophysiological disorders including type 2 diabetes and cardiovascular disease. Obese individuals, particularly those with excess adipose tissue around their major organs, lose the ability to respond to insulin and eventually develop hyperinsulinemia and hyperlipidemia. If left untreated, these individuals are at risk for developing type 2 diabetes and cardiovascular disease. Investigations during the last few years have focused on the adipocyte as a potential link between obesity and insulin resistance. The conclusions drawn from this research implicate the adipocyte as a central player in the development of insulin resistance, affecting muscle and liver of individuals with excess adipose tissue. In fact, the role of the adipocyte in regulating overall energy balance has been significantly redefined. Specifically, in addition to storing excess energy as triglycerides, adipocytes secrete many biologically active molecules that regulate mechanisms related to energy balance in other metabolically active tissues including the brain, muscle, and liver. These bioactive molecules include hormones and several cytokines, collectively referred to as
adipocytokines
, which include leptin, tumor necrosis factor α (TNF‐α), adiponectin/ACRP30/adipoQ/apM1, and resistin. Certain adipocytokines have been directly linked to insulin resistance in obese humans as well as in various animal models. An approach to combating type 2 diabetes mellitus, therefore, is to understand the molecular and physiological mechanisms that regulate the formation and function of adipocytes in specific adipose tissue depots. This chapter discusses the role of adipogenic transcription factors in regulating adipogenesis and metabolic homeostasis. Attention is given to the nuclear hormone receptor PPAR‐γ (peroxisome proliferator‐activated receptor γ) which is a master regulator of adipocyte differentiation and the target of the thiazolidinedione family of antidiabetic drugs. In this regard, the mechanism of action of the thiazolidinediones is discussed and other adipocyte proteins are proposed as alternative targets for the development of antidiabetic therapeutics.
Animal Models of Obesity
Authors: York David A. 
Published: August 2003

AbstractAnimal models have played an important role in advancing our understanding of the causes and consequences of obesity. The spontaneous single gene mutations led to the discovery of leptin and the melanocortin signaling pathways and were important to the understanding of hypothalamic systems that control energy balance. The use of transgenic and gene targeting technologies has opened a new era of investigation, identifying new genes that regulate the development or prevention of obesity and providing the tools for proof of function of genes. These studies have shown that a wide range of genes expressed primarily in the central nervous system or in adipose tissue are potential targets for the treatment of obesity.
Is Type 2 Diabetes the Result of a “Thrifty Genotype” or a “Thrifty Phenotype”?
Authors: Lindsay Robert S. 
Published: August 2003

AbstractWhile a number of important risk factors for development of type 2 diabetes have been described—most notably overweight and obesity—much of the detail of the etiology of the disease remains unknown. Both genetic and environmental factors will be important and disease risk is likely to reflect a complex interaction of both. Certain aspects of the epidemiology of type 2 diabetes, the widespread predisposition to the disease, increased predisposition in certain ethnic groups, and more recently, well‐described associations of diabetes risk and lower birth weight have prompted a number of hypotheses. These hypotheses attempt to explain these important epidemiological features of type 2 diabetes but also place our understanding of the etiology of type 2 diabetes in a wider context. A unifying theme of the thrifty genotype and thrifty phenotype hypotheses is the concept that predisposition to type 2 diabetes may reflect previous nutritional conditions. In the case of the thrifty genotype the nutritional history of populations favors genetic polymorphisms, which also render individuals diabetes prone. By contrast the thrifty phenotype proposes that adverse nutritional conditions in the early environment predispose to later disease in individuals. Both hypotheses are connected by a further underlying aim—to aid our understanding of the causes of type 2 diabetes and thus find ways to prevent, treat, and ultimately cure the disease.
Treatment of Obesity
Authors: Astrup Arne 
Published: August 2003

AbstractObesity is the major environmental factor in the development of type 2 diabetes in high‐risk subjects and even a minor weight loss can prevent the disease. Randomized trials using diet, weight loss agents, or surgical treatment of obesity have all clearly demonstrated that body fat loss is crucial in improving insulin resistance and reducing the risk of diabetes, whereas diet composition and physical activity play minor roles. Weight loss improves glycemic control in type 2 diabetic patients and has a clinically relevant beneficial effect on all cardiovascular risk factors. Weight management programs are a cornerstone in both the prevention and treatment of type 2 diabetes. A professional team (physician and dieticians or nurses) specializing in weight loss and maintenance can help almost all simple and diabetic obese patients achieve a weight loss of 5–10%. Higher daily physical activity levels and regular exercise increase daily energy expenditure and enhance insulin sensitivity in weight maintenance, but have no significant effect on rate of weight loss. Weight loss drugs have a role in the treatment of patients in whom lifestyle modification fails to produce the required weight control. Bariatric surgery is a very effective means to produce a longer lasting weight loss, and may be an option in severely obese patients who are difficult to treat with the other weight management tools.
Lipodystrophies and Diabetes
Authors: Garg Abhimanyu , Misra Anoop 
Published: August 2003

AbstractLipodystrophies are heterogeneous disorders of adipose tissue, characterized by selective loss of body fat and a predisposition to develop insulin resistance, diabetes mellitus, hyperlipidemia, and hepatic steatosis. These disorders can be either genetic or acquired. The extent of fat loss can also vary from being localized or partial to generalized. Among the genetic lipodystrophies, congenital generalized lipodystrophy is caused by mutations in 1‐acylglycerol‐3‐phosphateO‐acyltransferase 2 (AGPAT2) and Berardinelli–Seip Congenital Lipodystrophy 2 (BSCL2) genes and familial partial lipodystrophies by defects in lamin A/C (LMNA) and peroxisome proliferator‐activated receptor γ (PPARG) genes. Acquired generalized and partial lipodystrophies are likely to be autoimmune diseases. Lipodystrophy in HIV‐infected patients is mainly due to prolonged treatment with HIV‐1 protease inhibitors. Diabetes in patients with lipodystrophies may be caused by severe insulin resistance (hepatic and peripheral) and decrease in the insulin secretion due to pancreatic islet amyloidosis and β‐cell atrophy. Hyperglycemia is difficult to manage despite large doses of insulin but does not lead to ketosis. Recombinant human leptin has been reported to drastically improve hyperglycemia and hypertriglyceridemia in lipodystrophy patients with low serum leptin levels. It is hoped that our understanding of the pathogenesis of these disorders will contribute to a better understanding of adipocyte physiology, and of the molecular mechanisms of insulin resistance and eventually to better therapeutic options.
Clinical Features and Treatment of Coronary Heart Disease in Diabetes
Authors: Gray Rosaire P. , Yudkin John S. 
Published: August 2003

AbstractMorbidity and mortality from cardiovascular disease are two to five times higher in patients with diabetes mellitus compared with nondiabetic patients. The atherosclerotic lesion in diabetes mellitus is histologically similar to that in nondiabetic populations but is more extensive and severe. There is clustering of the major risk factors for cardiovascular disease, smoking, hypertension, and hyperlipidemia in diabetic subjects but the excess risk of coronary heart disease (CHD) remains after adjusting for levels of all other known risk factors, suggesting that diabetes is an independent risk factor for cardiovascular disease. The clinical manifestations of CHD are similar to that in nondiabetic subjects; however, silent ischemia and myocardial infarction are more common. The principles of management of angina, acute coronary syndromes, myocardial infarction, and heart failure are similar to that in the nondiabetic population. Until recently, most of the large randomized trials that have evaluated primary and secondary prevention therapies have not randomized large numbers of diabetic subjects and therefore much of the evidence is based on subgroup analysis and extrapolation from nondiabetic populations. A number of publications exist to guide primary and secondary prevention of CHD in the general population and these are summarized with particular reference to the diabetic patient, with emphasis on aggressive reduction of risk factors. Indications for coronary angiography in diabetic patients with symptomatic coronary disease are similar to those in nondiabetic patients, recognizing the increased risk associated with revascularization procedures in diabetes mellitus. There is an increased risk of mortality following both coronary bypass surgery and angioplasty, and there is a substantially increased risk of restenosis following angioplasty in diabetic patients, probably partly ameliorated by the use of coronary stents. Much of this increased risk is due to confounding associations, e.g. female sex, diffuse coronary disease, impaired left ventricular function, and renal impairment, rather than the diabetic state itself.
Peripheral Vascular Disease in Diabetes
Authors: Schaper Nicolaas C. , Kitslaar Peter J.E.M 
Published: August 2003

AbstractPeripheral arterial disease is a common finding in patients with diabetes mellitus. In many patients the disease has no or few symptoms and runs a relatively benign course. However, in others it leads to gangrene or impaired healing of a neuro‐ischemic foot ulcer, with amputation as a final result. Moreover, peripheral arterial disease (PAD) can be seen as a sign of severe generalized atherosclerosis, which should be treated aggressively. Peripheral arterial disease of the lower extremities, here abbreviated as PAD, is defined as signs, symptoms, or abnormal noninvasive tests in one or both legs attributable to obstructive atherosclerotic disease. Critical limb ischemia was recently defined as chronic ischemic rest pain, ulceration, or gangrene attributable to objectively proven arterial occlusive disease. The term critical limb ischemia implies chronicity. In contrast, acute limb ischemia is a sudden event, usually due to an embolus or thrombosis in preexistent PAD. In this chapter we discuss basic and clinical aspects of PAD in diabetic patients, with the patient in a diabetic clinic as a starting point. In the treatment of these patients a close cooperation between diabetologist and vascular surgeon is needed. Therefore, background information is given on several surgical procedures.
Hemostatic Abnormalities in Diabetes
Authors: Juhan‐Vague Irène , Emmanuel Morange Pierre , Alessi Marie‐Christine 
Published: August 2003

AbstractInsulin‐ and non‐insulin‐dependent diabetes and obesity with insulin resistance are accompanied by a prothrombotic state that favors thrombosis at the site of a suddenly ruptured atherosclerotic plaque and is also involved in the progression of atherosclerosis itself. This dysregulation of hemostasis includes activation of endothelial cells, leukocytes, and platelets, hypercoagulability with increased formation of the multipotent thrombin, and decreased fibrinolytic activity due to increased plasma levels of plasminogen activator inhibitor 1 (PAI‐1). The long‐lasting influence of these disorders exerts a progressive deleterious influence on the atherothrombotic process.The mechanisms that induce this prothrombotic state are multifactorial:Hyperglycemia leads to glycation of membrane and circulating proteins, inducing consequent functional changes and inflammation.Low‐grade inflammation with prolonged cytokine‐mediated acute phase reaction leads to cell activation and increased synthesis of hemostatic parameters such as fibrinogen, the main substrate of thrombin, von Willebrand Factor, and factor VIII.Insulin resistance also involves proinflammatory cytokines such as the tumor necrosis factor pathway, which could be the cause of the observed dramatic decrease in fibrinolysis due to increased expression of PAI‐1. Studies conducted in mice or epidemiological studies have shown recently that increased plasma PAI‐1 levels and increased PAI‐1 expression in tissues could influence adipose tissue growth and the development of atherosclerosis as well as that of type 2 diabetes. Thus, PAI‐1 could represent a target for therapeutic intervention.
Cerebrovascular Disease in Diabetes Mellitus
Authors: Gray Christopher S. 
Published: August 2003

AbstractDiabetes mellitus is an important risk factor for ischemic stroke. For many diabetic patients stroke is a recurrent disorder leading to cumulative disability, cognitive impairment, and reduced quality of life. Diabetic patients are also at increased risk of vascular dementia through processes that extend beyond clinically manifest and silent stroke and overlap with the pathophysiological changes of Alzheimer's type pathology. There is as yet no evidence that intensive control of diabetes can prevent vascular dementia. The extent to which diabetes is a risk factor for stroke is often underrecognized and many patients may not receive optimal secondary preventive treatment. Strategies to reduce the risk of first ever and recurrent stroke in diabetic subjects have now been clarified in large randomized controlled trials. Intensive management of hypertension and dyslipidemia has been shown to independently reduce the risk of cerebrovascular disease. For patients who have had a stroke, hyperglycemia with or without a previous history of diabetes is a frequent finding and is associated with a poor prognosis. Hyperglycemia may also adversely influence the safety and efficacy of other stroke treatments. The benefit of routine treatment to reverse this association is not as yet proven.
Metabolic Stress and Atherosclerosis
Authors: Reusch Jane E.-B. , Brownlee Michael 
Published: August 2003

AbstractDiabetes is associated with accelerated atherosclerotic macrovascular disease affecting arteries that supply the heart, brain, and lower extremities. As a consequence, patients with diabetes have a much higher risk of myocardial infarction, stroke, and limb amputation. The excess risk associated with diabetes remains even after adjustment for traditional coronary heart disease risk factors such as smoking, hypertension, and hypercholesterolemia. Type 2 diabetic patients without a previous myocardial infarction have as high a risk of myocardial infarction over 7 years as nondiabetic patients with a previous myocardial infarction. Type 1 diabetes results in nearly 100% atherosclerosis by the fifth decade of life. The mechanisms by which diabetes confers this increased risk are much less clear than those responsible for diabetic microvascular disease, but associational studies suggest that the metabolic derangements caused by insulin resistance and insulin deficiency are involved. These include dyslipoproteinemia, excess free fatty acid flux, and hyperglycemia. In this chapter we review recent findings on the mechanisms whereby high glucose and high FFAs, present in both type 1 and type 2 diabetes, lead to vascular dysfunction and injury. Pathways involving advanced glycation end products, protein kinase C, NF‐κB, aldose reductase, hexosamine, and CREB (cAMP response element binding protein) are reviewed. Both hyperglycemia and high free fatty acid flux lead to increased vascular oxidative stress, which appears to activate all of these signaling pathways, leading to diabetic macrovascular disease.
Organization of Care: Problems in Developing Countries—Sub‐Saharan Africa
Authors: Mbanya Jean Claude 
Published: August 2003

Abstract
Diabetes mellitus is now a major health problem in Africa, and patient numbers will increase with the tremendous gain in life expectancy. Africa had a population of nearly 600 million inhabitants in 1998, with an estimated diabetic population of 550 000 type 1 and 5 million type 2 diabetic patients. With the current trends, it is estimated that the African diabetic population would more than double by the year 2000 and quadruple by the year 2010. Yet the health care system of most countries in the region is geared mostly toward communicable diseases. Diabetes care is integrated in the overall national health care structures, with primary care bearing the main responsibility. Diabetic patients seek care at the primary, district, or tertiary health care systems where there are geographical disparities in the availability, organization, and quality of diabetes care. Delivery of diabetes care is fraught with problems including organizational, medical, socioeconomic, cultural, and geographic factors. Governments, diabetes associations, and other bodies comprising people affected with diabetes, physicians, nurses, nutritionists, and educators should cooperate with one another in improving diabetes care in the region.
Arsenic Tolerating Plants from Mine Sites and Hot Springs in the Semi‐Arid Region of Chihuahua, Mexico
Authors: Flores‐Tavizón E. , Alarcón‐Herrera M. T. , González‐Elizondo S. , Olguín E. J. 
Published: August 2003

AbstractPhytoremediation is an emergent field of great potential for the removal of metals, metalloids and other contaminants from soil, water and sediments. The use of native plants with high tolerance and capacity to accumulate the metal to be removed is a very convenient approach. High levels of arsenic (As) have been found at several natural sources in the northern arid and semi‐arid regions of Mexico. The state of Chihuahua is, among others, one in which As has been detected in sources of natural drinking water. The aim of the present work was to identify indigenous plants in the state of Chihuahua with As tolerance and accumulating capacity. Water samples from different mine sites and hot springs were inspected. At these sites, the As concentration varied in the range of 110–191 μg/l in water and 40–2100 μg/g in soils. A native plant identified as Eleocharis sp. (Cyperaceae), collected from the nearby surroundings of a hot spring site, was found to contain an As concentration of 301 μg/g. The arsenic bioconcentration (BCF) and translocation (TF) factors for this plant exceeded 1 (5.22 and 7.37, respectively), which classifies it as an arsenic‐tolerant plant with potential use in phytoextraction. The TF of Brickellia veronicaefolia, Nicotiana glauca and Baccharis salicifolia were above one, but they had very low BCF coefficients, which limited their potential to be considered for a phytoremediation process.
Bioluminescence Biosensor for the Detection of Organomercury Contamination
Authors: Endo G. , Yamagata T. , Narita M. , Huang C.‐C. 
Published: August 2003

AbstractTo selectively detect organomercurial compounds in the environment, in this study a bioluminescence biosensor for organomercurials was developed using a bacterial gene expression system for the mercury resistance determinant. merB3‐Luciferase (mer‐lux) transcriptional fusion plasmids pHYΔ3Lux and pHY.Δ3Lux were constructed to evaluate the gene expression system with a new organomercury lyase gene merB3 from Bacillus megaterium strain MB1, which is resistant to a broad spectrum of mercury compounds, and with its 3'end‐deleted defective merB3, respectively. Another plasmid, pGR1A, encoding an operator/promoter sequence, merR1, merE, merT, merP and merA from the same bacterial strain was constructed and used as a transacting gene expression vector which combines the gene expression vector of mer‐lux transcriptional fusion plasmids in the same Escherichia coli cells. The transformants that carried a set of the two plasmids were used as biological sensors for the detection of organomercurials. Transformant (E. coli DH5α/pHYB3Lux, pGR1A) is available to distinguish the organomercury from inorganic mercury, since inorganic mercurials can induce the bioluminescence of both the bacterial strain lines with pHYΔB3Lux and pHYB3Lux, whereas organomercurials can only induce the bioluminescence of the lines with pHYB3Lux. These experimental results showed that the transformant with a merB3‐defective fusion plasmid, and the gene expression vector responded to only mercury chloride. On the other hand, the transformant with an intact merB3 fusion plasmid and the gene expression vector responded to mercury chloride and all organomercurials tested in the study. The sensor system responded to the existence of the phenyl mercury acetate of 50 nanomolar and was more sensitive than that of inorganic mercury (100 nanomolar). The result also indicated the capability of the system to detect bio‐affecting inorganic mercury from several hundred nanomolar to several ten micromolar.
Biological Removal of Nitrogen to Improve the Quality of Reclaimed Wastewater for Groundwater Recharge
Authors: Espino‐Valdés M. S. , Manzanares‐Papayanópoulos L. I. , Nevárez‐Moorillón G. V. , Keer‐Rendón A. , Bautista‐Margulis R. 
Published: August 2003

AbstractNitrogen removal was studied in a pilot scale continuous flow system consisting of two reactors in series for nitrification and denitrification. The system was used to eliminate ammonia, nitrate and nitrite from a secondary wastewater effluent.The first stage of the process consisted of an aerobic upflow bioreactor with an autotrophic nitrifying population for ammonia oxidation, which was grown on silica sand granules and produced during the growth process nitrite and nitrate. During the second stage, these oxidised forms of nitrogen were successfully reduced to nitrogen gas in an anoxic denitrification fluidised bed reactor. At this stage, methanol was added as an external carbon source for the heterotrophic organisms growing on a silica sand support.The optimum nitrification efficiency was 91% for the highest ammonia concentration at the influent (51 mg NH3‐N/l) and a retention time of 3.7 hours. With a lower ammonia concentration (23 mg NH3‐N/l), the highest nitrification efficiency was 95% corresponding to 1.1 mg NH3‐N/l in the nitrified effluent. In the denitrification process, a 95% removal efficiency of nitrite and nitrate for 55 mg NOx‐N/l at 2.3 hours and a concentration of microorganisms in the reactor of approx. 6,000 mg VSS/l was obtained. As a complementary stage of the nitrogen removal process, a silica sand and powderactivated carbon filter was installed in order to improve the quality of the final effluent in terms of other properties like turbidity, colour and the content of organic matter.