Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence suggests that impaired lipolysis may contribute to fat accumulation. To test whether the lipolytic response to adrenergic stimulation is lower in Pima Indians, a population prone to obesity and type 2 diabetes mellitus, than in Caucasians, 48 healthy, non-diabetic subjects were studied: 27 Pima Indians (12 males and 15 females, 30 +/- 7 yr, 85 +/- 18 kg, 36 +/- 10% body fat; mean +/- SD) and 21 Caucasians (11 males and 10 females, 34 +/- 7 yr, 105 +/- 26 kg, 39 +/- 11% body fat). Lipolysis in the abdominal s.c. adipose tissue was assessed in situ by glycerol concentration in microdialysis samples at baseline and during local infusion of the nonselective beta-adrenergic agonist isoproterenol (10(-6) mol/L), mental stress, and submaximal exercise. The baseline dialysate glycerol concentrations were similar in Pima Indians and Caucasians. Lipolytic response (relative increment in dialysate glycerol concentration, percentage above the baseline) was similar in Pima Indians and Caucasians in response to local isoproterenol infusion (77 +/- 36% and 76 +/- 40%) and exercise (38 +/- 38% and 41 +/- 41%). During mental stress, the dialysate concentration did not change significantly from baseline in either group. Changes in local blood flow, determined by ethanol dilution, did not differ between the two groups. In conclusion, the high propensity for obesity in Pima Indians does not seem to be due to an impaired lipolytic response to stimuli.
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PMID:In situ lipolytic responses to isoproterenol and physiological stressors are similar in obese Pima Indians and Caucasians. 981 91

As compared to subcutaneous adipocytes, visceral adipocytes have high basal lipolysis, are highly sensitive to catecholamines, and are poorly sensitive to insulin; these traits are amplified when visceral adipocytes hypertrophy. As a result, enlarged visceral fat stores tend to flood the portal circulation with free fatty acids at metabolically inappropriate times when fatty acids are unlikely to be oxidized, thus exposing tissues to excessive free fatty acid levels and giving rise to the insulin resistance syndrome. A logical approach to preventing or correcting visceral obesity is to down-regulate the lipoprotein lipase (LPL) activity of visceral adipocytes relative to that expressed in subcutaneous adipocytes and skeletal muscle. IGF-I activity appears to be a primary determinant of visceral LPL activity in humans; systemic IGF-I activity is decreased when diurnal insulin secretion is low, when hepatocytes detect a relative paucity of certain essential amino acids, and when estrogens are administered orally. The ability of alpha-glucosidase inhibitor therapy to selectively reduce visceral adiposity suggests that down-regulation of diurnal insulin secretion and/or IGF-I activity may indeed have a greater impact on LPL activity in visceral fat than in subcutaneous fat. Thus, low-glycemic-index, vegan, high-protein, or hypocaloric diets can be expected to decrease visceral LPL activity, as can postmenopausal estrogen therapy. Furthermore, estrogen enhances the LPL activity of non-pathogenic gluteofemoral fat cells, whereas testosterone decreases visceral LPL activity in men; this may explain why sex hormone replacement in middle-aged people of both sexes has a favorable impact on visceral fat and insulin sensitivity. Beta-adrenergic activity suppresses transcription of LPL in adipocytes; this phenomenon may contribute to the favorable impact of exercise training on visceral obesity; conceivably, preadministration of safe drugs that boost catecholamine activity (caffeine, yohimbine) could potentiate this beneficial effect of exercise. Glucocorticoids selectively increase the LPL activity of visceral adipocytes; while there is currently no convincing evidence that psychological stress is a major determinant of visceral adiposity, or that stress management techniques can help to correct visceral obesity, reports that anxiolytic therapy can improve glycemic control in type 2 diabetes should encourage further research along these lines.
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PMID:Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. 1146 Nov 72

A wide variety of stresses are prevalent in the environment that could change the course and phenotypic expression of metabolic diseases. Amongst the various stresses the oxidative stress plays a pivotal role in the disease progression through free radical generation and may lead to various metabolic disorders such as non-insulin dependent diabetes mellitus, cardiovascular diseases, hypertension obesity, stroke, etc. Psychological stress has been implicated as a root cause of several psychosomatic disorders. Thus there cannot be a life without stress. Under such a scenario of stressful conditions further fueled by life style changes we propose to counteract any kind of stress by another milder form of stress that is likely to protect the cells from drastic effects of severe stress. Here we hypothesize that the beta-cells of islets of Langerhans can be protected from the diabetogenic insults and oxidative stress by inducing a protective stress response such as heat shock through dietary interventions.
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PMID:Can stress provide protection to pancreatic beta-cells and prevent diabetes? 1258 12

In previous publications, we presented the hypothesis that repeated episodes of acute or chronic psychological stress could induce an acute phase response (APR) and subsequently a chronic inflammatory process such as atherosclerosis. In this paper, that hypothesis, namely that such stress can induce an APR and inflammation, has been extended to include a chronic inflammatory process(s), characterized by the presence of certain cytokines and acute phase reactants (APR), which is associated with certain metabolic diseases. The loci of origin of these cytokines, particularly interleukin 6 (IL-6), and their induction, has been considered. Evidence is presented that the liver, the endothelium, and fat cell depots are the primary sources of cytokines, particularly IL-6, and that IL-6 and the acute phase protein (APP), C-reactive protein (CRP), are strongly associated with, and likely play a dominant role in, the development of this inflammatory process which leads to insulin resistance, non-insulin dependent diabetes mellitus type II, and Metabolic syndrome X. The possible role of psychological stress and the major stress-related hormones as etiologic factors in the pathogenesis of these metabolic diseases, as well as atherosclerosis, is discussed. The fact that stress can activate an APR, which is part of the innate immune inflammatory response, is evidence that the inflammatory response is contained within the stress response or that stress can induce an inflammatory response. The evidence that the stress, inflammatory, and immune systems all evolved from a single cell, the phagocyte, is further evidence for their intimate relationship which almost certainly was maintained throughout evolution.
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PMID:The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. 1294 57

There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
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PMID:Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. 1498 10

Elevated plasma free fatty acid (FFA) concentrations as seen in obesity, insulin resistance, and type 2 diabetes are partly caused by impaired inhibition of intracellular lipolysis in adipose tissue, and this is considered to be part of the insulin resistance syndrome (IRS). Based on predicted insulin resistance at the level of intracellular lipolysis, patients with the IRS would loose weight by disinhibited lipolysis. Since this is not the case in clinical practice, impaired stimulation of intracellular lipolysis must also play a role. We studied acute plasma FFA changes, representing stimulation and inhibition of intracellular adipose tissue lipolysis, in obese patients with IRS and in healthy controls. Thirteen insulin-resistant (IR) subjects (7 men and 6 women) and 10 controls (6 men and 4 women) underwent a mental stress test (20 minutes) preceded by 60 minutes of rest. After mental stress, an oral glucose tolerance test (OGTT) was performed. Baseline FFA levels were higher in IR patients compared to controls (0.59 +/- 0.06 and 0.31 +/- 0.06 mmol/L, respectively; P =.004). During the 20 minutes of mental stress, FFAs increased significantly in IR subjects from 0.55 +/- 0.07 to 0.67 +/- 0.07 mmol/L (P <.001) and from 0.21 +/- 0.04 to 0.36 +/- 0.07 mmol/L in controls (P =.001). Although the absolute change of plasma FFA was not different, the relative increase was lower in IR subjects (28% +/- 7%) compared to controls (89 +/- 24%; P =.02). Despite the more pronounced mean maximal insulin concentration during the OGTT in IR subjects compared to controls (600.0 +/- 126.6 pmol/L and 208.1 +/- 30.0 pmol/L, respectively), the relative decrease of FFAs was lower in IR subjects (11% +/- 5% v 36% +/- 11% in controls after 30 minutes; P =.04). In conclusion, our study shows impaired acute responses of plasma FFAs upon stimulation by mental stress and inhibition by endogenous insulin in insulin resistance in vivo. The presence of both defects helps to understand weight maintenance in insulin resistance.
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PMID:In vivo regulation of plasma free fatty acids in insulin resistance. 1533 84

n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), mainly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), are present in mammal tissues both from endogenous synthesis from desaturation and elongation of 18:3 n-3 and/or from dietary origin (marine products and fish oils). In rodents in vivo, n-3 LC-PUFA have a protective effect against high fat diet induced insulin resistance. Such an effect is explained at the molecular level by the prevention of many alterations of insulin signaling induced by a high fat diet. Indeed, the protective effect of n-3 LC-PUFA results from the following: (a) the prevention of the decrease of phosphatidyl inositol 3' kinase (PI3 kinase) activity and of the depletion of the glucose transporter protein GLUT4 in the muscle; (b) the prevention of the decreased expression of GLUT4 in adipose tissue. In addition, n-3 LC-PUFA inhibit both the activity and expression of liver glucose-6-phosphatase which could explain the protective effect with respect to the excessive hepatic glucose output induced by a high fat diet. n-3 LC-PUFA also decrease muscle intramyofibrillar triglycerides and liver steatosis. This last effect results on the one hand, from a decreased expression of lipogenesis enzymes and of delta 9 desaturase (via a depleting effect on sterol response element binding protein 1c (SREBP-1c). On the other hand, n-3 LC-PUFA stimulate fatty acid oxidation in the liver (via the activation of peroxisome proliferator activated receptor alpha (PPAR-alpha)). In patients with type 2 diabetes, fish oil dietary supplementation fails to reverse insulin resistance for unclear reasons, but systematically decreases plasma triglycerides. Conversely, in healthy humans, fish oil has many physiological effects. Indeed, fish oil reduces insulin response to oral glucose without altering the glycaemic response, abolishes extraggression at times of mental stress, decreases the activation of sympathetic activity during mental stress and also decreases plasma triglycerides. These effects are encouraging in the perspective of prevention of insulin resistance but further clinical and basic studies must be designed to confirm and complete our knowledge in this field.
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PMID:N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? 1546 Jan 68

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
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PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

Negative affective states such as depression are associated with premature mortality and increased risk of coronary heart disease, type 2 diabetes, and disability. It has been suggested that positive affective states are protective, but the pathways through which such effects might be mediated are poorly understood. Here we show that positive affect in middle-aged men and women is associated with reduced neuroendocrine, inflammatory, and cardiovascular activity. Positive affect was assessed by aggregating momentary experience samples of happiness over a working day and was inversely related to cortisol output over the day, independently of age, gender, socioeconomic position, body mass, and smoking. Similar patterns were observed on a leisure day. Happiness was also inversely related to heart rate assessed by using ambulatory monitoring methods over the day. Participants underwent mental stress testing in the laboratory, where plasma fibrinogen stress responses were smaller in happier individuals. These effects were independent of psychological distress, supporting the notion that positive well-being is directly related to health-relevant biological processes.
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PMID:Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes. 1584 Jul 27

Diabetic ketoacidosis (DKA) is the most common hyperglycemic emergency in patients with diabetes mellitus. DKA most often occurs in patients with type 1 diabetes, but patients with type 2 diabetes are susceptible to DKA under stressful conditions, such as trauma, surgery, or infections. DKA is reported to be responsible for more than 100 000 hospital admissions per year in the US, and accounts for 4-9% of all hospital discharge summaries among patients with diabetes. Treatment of patients with DKA uses significant healthcare resources and accounts for 1 out of every 4 healthcare dollars spent on direct medical care for adult patients with type 1 diabetes in the US. Recent studies using standardized written guidelines for therapy have demonstrated a mortality rate of less than 5%, with higher mortality rates observed in elderly patients and those with concomitant life-threatening illnesses. Worldwide, infection is the most common precipitating cause for DKA, occurring in 30-50% of cases. Urinary tract infection and pneumonia account for the majority of infections. Other precipitating causes are intercurrent illnesses (i.e., surgery, trauma, myocardial ischemia, pancreatitis), psychological stress, and non-compliance with insulin therapy. The triad of uncontrolled hyperglycemia, metabolic acidosis and increased total body ketone concentration characterizes DKA. These metabolic derangements result from the combination of absolute or relative insulin deficiency and increased levels of counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Successful treatment of DKA requires frequent monitoring of patients, correction of hypovolemia and hyperglycemia, replacement of electrolyte losses, and careful search for the precipitating cause. Since the majority of DKA cases occur in patients with a known history of diabetes, this acute metabolic complication should be largely preventable through early detection, and by the education of patients, healthcare professionals, and the general public. The frequency of hospitalizations for DKA has been reduced following diabetes education programs, improved follow-up care, and access to medical advice. Novel approaches to patient education incorporating a variety of healthcare beliefs and socioeconomic issues are critical to an effective prevention program.
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PMID:Diabetic ketoacidosis: risk factors and management strategies. 1587 46


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