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

The glucokinase regulator (GCKR) is a 65-kDa protein that inhibits glucokinase (hexokinase IV) in liver and pancreatic islet. The role of glucokinase (GCK) as pancreatic beta cell glucose sensor and the finding of GCK mutations in maturity onset diabetes of the young (MODY) suggest GCKR as a further candidate gene for type 2 diabetes. The inhibition of GCK by GCKR is relieved by the binding of fructose-1-phosphate (F-1-P) to GCKR. F-1-P is the end product of ketohexokinase (KHK, fructokinase), which, like GCK and GCKR, is present in both liver and pancreatic islet. KHK is the first enzyme of the specialized pathway that catabolizes dietary fructose. We have isolated genomic clones containing the human GCKR and KHK genes. By fluorescent in situ hybridization (FISH), KHK maps to Chromosome (Chr) 2p23.2-23.3, a new assignment corroborated by somatic cell hybrid analysis. The localization of GCKR, originally reported by others as 2p22.3, has been reassessed by high-resolution FISH, indicating that, like KHK, GCKR maps to 2p23.2-23.3. The proximity of GCKR and KHK was further demonstrated both by two-color interphase FISH, which suggests that the two genes lie within 500 kb of each other, and by analysis of overlapping YAC and P1 clones spanning the interval between GCKR and KHK. A new microsatellite polymorphism was used to place the GCKR-KHK locus between D2S305 and D2S165 on the genetic map. The colocalization of these two metabolically connected genes has implications for the interpretation of linkage or allele association studies in type 2 diabetes. It also raises the possibility of coordinate regulation of GCKR and KHK by common cis-acting regulatory elements.
 ...
PMID:Co-localization of the ketohexokinase and glucokinase regulator genes to a 500-kb region of chromosome 2p23. 866 30

In Western countries, chronic coronary artery disease (CAD) has a prevalence of 3-4%. The aims of treatment of chronic CAD are (1) improvement of quality of life by preventing anginal pain, by maintaining exercise capability, and by reducing anxiety; (2) decrease of cardiovascular morbidity, especially by avoiding myocardial infarction and development of heart failure; (3) reduction of mortality. These goals can be achieved by (a) cardiovascular risk reduction, especially management of risk factors, (b) optimal medical therapy, (c) coronary revascularization, (d) periods of rehabilitation, and (e) outpatient long-term observation and treatment. The patient has a good chance to improve the natural course of his disease by changing his lifestyle. In this regard, physical exercise, weight reduction and smoking cessation have to be mentioned first. Furthermore, the cardiovascular risk may significantly be diminished by adequate treatment of hyperlipoproteinemia: lowering of plasma LDL cholesterol levels in patients with chronic CAD is associated with a retarded progression of atherosclerosis as well as a decrease of cardiovascular events by 30-40% and lower mortality (by up to 34%). In patients with CAD and/or type 2 diabetes, statin therapy leads to a significant improvement of prognosis independent of the basal value of LDL cholesterol. Improved diet and adequate medical therapy may also result in diminished cardiovascular risk. By means of physical activity, mortality and morbidity of CAD can also be significantly reduced. The antianginal medication in patients with chronic CAD consists of nitrates, beta-blockers, and calcium channel blockers. In order to prevent myocardial infarction and death (secondary prevention), antiplatelet agents, renin-angiotensin-aldosterone system blockers, as well as cholesterol-lowering drugs are applied. In this paper, the guidelines of the American College of Cardiology/American Heart Association, the European Society of Cardiology and the NVL-KHK (German) guidelines regarding prevention, medical therapy and coronary artery revascularization procedures are summarized. Do the guidelines reflect daily practice? To answer this question, the following topics are discussed: (1) Management of risk factors with respect to available guidelines, (2) missing evidence from randomized controlled trials for medical therapy options widely used in clinical practice, (3) guideline-compliant use or underuse of diagnostic assessment, medical therapy and revascularization procedures, (4) gender bias in indications for percutaneous coronary interventions and in the use of investigations/evidence-based medical therapy, and (5) nonadherence to existing guidelines.
 ...
PMID:Treatment of chronic CAD--do the guidelines (ESC, AHA) reflect daily practice? 1921 8