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)

The term X syndrome involves several dilemmas. The terminological dilemma is that this term is used to describe microvascular angina pectoris, as well as Reaven's metabolic-hormonal syndrome and our 5H syndrome [association of hyperinsulinism with arterial hypertension, hyperlipoproteinaemia, hyperglycaemia (NIDDM) and hirsutism]. It is probable that the coronary X syndrome is frequently conditioned by the hormonal-metabolic X syndrome. The pathogenetic dilemma is that it is not clear why in microvascular angina pectoris the coronary circulation does not possess an adequate reserve for vasodilatation during exercise or in response to some pharmacological stimuli. This could condition hyperinsulinism in hypertonic subjects with NIDDM with an early disorder of paracrine endothelial relaxation mechanisms (EDRF-NO), with a predominance of vasoconstrictor mechanisms (endothelin-1). In Reaven's syndrome X it is not clear whether insulin resistance of the postreceptor type is a primary inborn phenomenon which is compensated by insulin hypersecretion or whether it is a secondary phenomenon, which develops ex post and by which the target tissues defend themselves against an excessive effect of insulin (e.g. down regulation receptors) in primary disorders of its secretion.
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PMID:[The dilemma of syndrome X]. 149 65

Insulin resistance (IR) is a phenomenon which associates several serious "diseases of civilization" within the framework of Reaven's metabolic syndrome. In the submitted paper the authors describe the so-called "paradox of insulin resistance"--a paradoxical finding of inadequate insulin action under laboratory induced conditions while under "common" conditions the finding is reversed. Diabetes mellitus type 2 (with obesity) is characterized by excessive filling of cells by energetically rich substances. A low energy output, inadequate physical activity in these subjects leads to the development of regulatory mechanisms, which restrict further nutrient (glucose) uptake from blood into cells. During subsequent stages of the disease the excessive glucose uptake by adipose tissue cells and muscle is ensured by the high concentration gradient, hyperglycaemia and hyperinsulinaemia. Induction of "comparable" conditions in clamp studies leads to paradoxical results. During relative hypoglycaemia and hypoinsulinaemia (as compared with normal conditions) the tissues of the diabetic patient, due to regulatory mechanisms, take up a smaller amount of glucose than tissues of non-diabetic subjects (although under normal conditions the glucose uptake is higher). This phenomenon is called "Paradox of insulin resistance". In a major proportion of patients IR can be induced by mere maintenance of hyperinsulinaemia, it can be minimalized by reducing the nutrient intake and by increasing physical exertion. Differentiation of patients where IR is a secondary, regulatory phenomenon is one of the basic tasks of the physician. Only patients who suffer from primary disorders of insulin function, primary IR and true insulin deficiency should be treated by administration of hyperinsulinaemia inducing drugs. It is questionable how suitable it is to administer these drugs to patients who suffer from a life-style disorder and are threatened by complications associated with hyperinsulinism.
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PMID:[The paradox of insulin resistance]. 1095 72

Insulin orchestrates physiological responses to ingested nutrients; however, although it elicits widely ramifying metabolic and trophic responses from diverse tissues, 'insulin resistance (IR)', a pandemic metabolic derangement commonly associated with obesity, is usually defined solely by blunting of insulin's hypoglycaemic effect. Recent study of monogenic forms of IR has established that biochemical subphenotypes of IR exist, clustering into those caused by primary disorders of adipose tissue and those caused by primary defects in proximal insulin signalling. IR is often first recognised by virtue of its associated disorders including type 2 diabetes, dyslipidaemia (DL), fatty liver and polycystic ovary syndrome (PCOS). Although these clinically observed associations are confirmed by cross-sectional and longitudinal population-based studies, causal relationships among these phenomena have been more difficult to establish. Single gene IR is important to recognise in order to optimise clinical management and also permits testing of causal relationships among components of the IR syndrome using the principle of Mendelian randomisation. Thus, where a precisely defined genetic defect is identified that directly produces one component of the syndrome, then phenomena that are causally linked to that component should be seen. Where this is not the case, then a simple causal link is refuted. This article summarises known forms of monogenic severe IR and considers the lessons to be learned about the pathogenic mechanisms both upstream from common IR and those downstream linking it to disorders such as DL, fatty liver, PCOS and cancer.
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PMID:EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons. 2686 83