Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin action starts with binding to a membrane receptor (insulin receptor-tyrosine kinase) and with activating an insulin receptor substrate 1 (IRS-1) and substrate 2 (IRS-2). Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K. NIDDM can be defined as a disease caused by defective transduction of insulin signals and IR as a complex phenotype manifesting itself, emphasized by individual and environmental factors, in the cellular systems of signal transduction. IRS is a syndrome characterized by NIDDM, hypertension, visceral obesity, CHD: the X syndrome. Up to day the described mutations of the insulin-receptor gene are rare (e.g. the leprechaunism): genetic IR. Obesity is the principal cause of IR by receptorial and post-receptorial defects: metabolic IR. The obese skeletal muscle shows a reduction of insulin receptor and IRS-1 phosphorylation and of PI-3-K activation; the scarce expression of these proteins would determine the muscular IR. IR is a pattern of essential hypertension. Hypertension, dyslipidemia and abnormality of glucose metabolism are linked by IR. The so called high erythrocyte Na(+)-Li+ counter-transport is a new biochemical marker for IR and hypertension. These drugs can reduce IR: metformin, sulphonilureas, fibrats, dexfenfluramine, troglitazone, doxazosin, ACE-inhibitors.
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PMID:[Insulin resistance. Receptor and post-receptor abnormalities]. 984 54

PIH, the most common complication of pregnancy, remains a major source of maternal-child morbidity and mortality. Yet the etiology of this disorder is still little understood. There is now a growing body of evidence linking PIH and insulin resistance. Both proteinuric and non-proteinuric PIH predict future essential hypertension, and to a lesser extent, diabetes, disorders strongly related to glucose intolerance and insulin resistance. PIH is associated with diabetes, occurring in up to 50% of diabetic pregnancies. PIH is characterized by the same features that define IRS, including hypertension, dyslipidemia, disruption of endothelial and platelet function and related disturbances of prostanoid synthesis, coagulation and fibrinolytic abnormalities, hyperuricemia, atherosclerotic changes, and obesity. During the last decade, controlled studies by at least 11 different research groups in nine countries have established significant positive associations between both proteinuric and nonproteinuric PIH and various measures of insulin resistance. In particular, prospective investigations by at least five groups of investigators have indicated that relative hyperinsulinemia, glucose intolerance, and insulin insensitivity predict the subsequent development of PIH. These and other studies suggest that insulin resistance may play a causal role in the pathogenesis of PIH, and that some aspects of PIH may represent an early manifestation of IRS, precipitated by the profound metabolic and hemostatic challenges of gestation.
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PMID:Pregnancy-induced hypertension and insulin resistance: evidence for a connection. 1020 92

The insulin resistance (metabolic) syndrome (IRS), also known as syndrome X, is characterized by a clustering of factors associated with cardiovascular risk (obesity, impaired glucose metabolism, hypertension, and dyslipidemia). As reported from the third National Health and Nutrition Examination survey, the IRS is present in approximately 24% of adults in the United States and is strongly associated with coronary heart disease, stroke, type 2 diabetes, and all-cause mortality. Of equal importance, it is now clear that the origins of the IRS extend back into childhood (the IRS is found in approximately 4-10% of children and adolescents) and that the high prevalence of adult IRS is strongly linked to the development of cardiovascular risk during childhood and tracking of the components of the IRS into adulthood. The goal of this review is to present a summary of the currently available information on the IRS in the pre-adult age group with reference to adult studies only when necessary for clarification. The review will specifically summarize insulin resistance in childhood; the important influence of obesity and, in particular, visceral fat, on insulin resistance and the IRS; differences between ethnic groups; relations to adipocytokines, inflammatory factors and oxidative stress; relations of hypertension and lipids to insulin resistance; familial factors; endocrine complications; and potential therapeutic effects from diet and physical activity. Despite the lesser amount of basic and clinical information on childhood IRS in comparison to information available from adult studies, there can now be little doubt that the adverse associations among risk factors comprising the IRS begin in childhood. The challenge is to identify etiologic relations and develop intervention strategies designed to reduce the increasing prevalence of type 2 diabetes and cardiovascular disease.
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PMID:Insulin resistance (metabolic) syndrome in children. 1648 22

Patients with type 2 diabetes mellitus (T2DM) are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained CV risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained CV risk in patients with T2DM. Accordingly, CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of the insulin-sensitizing agents and of other antihyperglycemic medications on CV outcomes are discussed.
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PMID:Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents. 3105 Jul 6

Obesity is accompanied by dyslipidemia, hypoxia, endoplasmic reticulum (ER) stress, and inflammation, representing the major risk factor for the development of insulin resistance (IR) and type 2 diabetes. We modeled these conditions in cultured 3T3-L1 adipocytes and studied their effect on insulin signaling, glucose uptake, and inflammatory response via activation of stress-dependent JNK1/2 kinases. Decreased insulin-induced phosphorylation of the insulin cascade components IRS, Akt, and AS160 was observed under all tested conditions (lipid overloading of cells by palmitate, acute inflammation induced by bacterial lipopolysaccharide, hypoxia induced by Co2+, and ER stress induced by brefeldin A). In all the cases, except the acute inflammation, glucose uptake by adipocytes was reduced, and the kinetics of JNK1/2 activation was bi-phasic exhibiting sustained activation for 24 h. By contrast, in acute inflammation, JNK1/2 phosphorylation increased transiently and returned to the basal level within 2-3 h of stimulation. These results suggest a critical role of sustained (latent) vs. transient (acute) inflammation in the induction of IR and impairment of glucose utilization by adipose tissue. The components of the inflammatory signaling can be promising targets in the development of new therapeutic approaches for preventing IR and type 2 diabetes.
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PMID:Chemical Inducers of Obesity-Associated Metabolic Stress Activate Inflammation and Reduce Insulin Sensitivity in 3T3-L1 Adipocytes. 3123 69

The objective of current work was to explore the potential anti-diabetic mechanisms of Hizikia fusifarme polysaccharide (HFP) in type 2 diabetic rats. The carbohydrate loading experiment illustrated that HFP supplement could reduce blood sugar fluctuations caused by eating through inhibiting the hydrolysis of starch in mice. The analysis of typically diabetic symptoms and serum profiles showed that oral administration of HFP could mitigate hyperglycemia, insulin resistance, dyslipidemia, chronic inflammation and oxidative stress in rats. The 16s rRNA gene sequencing analysis indicated that HFP treatment could restore beneficial composition of gut flora in diabetic rats, and the correlation analysis revealed that the improvement of diabetes is closely related to the modification of gut flora by HFP intervention. Furthermore, the RT-qPCR and western blotting analysis clarified that HFP administration could increase glycogen storage in liver and skeletal muscle of diabetic rats through activating IRS/PI3K/AKT/GLUT signaling pathway and restrain gluconeogenesis via affecting the relative expression of Egr-1 and PEPCK genes.
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PMID:Mitigation mechanisms of Hizikia fusifarme polysaccharide consumption on type 2 diabetes in rats. 3284 81