Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced glycation end products (AGEs) are nonenzymatically glycosylated proteins, which accumulate in vascular tissues in aging and diabetes. Receptors for AGEs include scavenger receptors, which recognize acetylated low density lipoproteins (Ac-LDL) such as scavenger receptor class AI/AII (SR-A), cell surface glycoprotein CD36, scavenger receptor class B type I (SR-BI), and lectin-like oxidized low density lipoprotein receptor-1. The broad ligand repertoire of these receptors as well as the diversity of the receptors for AGEs have prompted us to examine whether AGEs are also recognized by the novel scavenger receptors, which we have recently isolated from a cDNA library prepared from human umbilical vein endothelial cells, such as the scavenger receptor expressed by endothelial cells-I (SREC-I); the fasciclin EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1 (FEEL-1); and its paralogous protein, FEEL-2. At 4 degrees C, (125)I-AGE-bovine serum albumin (BSA) exhibited high affinity specific binding to Chinese hamster ovary (CHO) cells overexpressing FEEL-1 (CHO-FEEL-1) and FEEL-2 (CHO-FEEL-2) with K(d) of 2.55 and 1.68 microg/ml, respectively, but not to CHO cells expressing SREC (CHO-SREC) and parent CHO cells. At 37 degrees C, (125)I-AGE-BSA was taken up and degraded by CHO-FEEL-1 and CHO-FEEL-2 cells but not by CHO-SREC and parent CHO cells. Thus, the ability to bind Ac-LDL is not necessarily a prerequisite to bind AGEs. The (125)I-AGE-BSA binding to CHO-FEEL-1 and CHO-FEEL-2 cells was effectively inhibited by Ac-LDL and polyanionic SR-A inhibitors such as fucoidan, polyinosinic acids, and dextran sulfate but not by native LDL, oxidized LDL, or HDL. FEEL-1, which is expressed by the liver and vascular tissues, may recognize AGEs, thereby contributing to the development of diabetic vascular complications and atherosclerosis.
 ...
PMID:FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. 1247 45

Diabetes, is a metabolic disorder characterised by chronic hyperglycaemia, hypertension, dyslipidaemia, microalbuminuria and inflammation. Moreover, there are a number of complications associated with this condition including retinopathy, neuropathy and nephropathy. Diabetic nephropathy, is the major cause of end-stage renal disease in Western societies affecting a substantial proportion (25-40%) of patients with diabetes. Advanced glycation end products (AGEs) have been identified as important modulators of the development and progression of diabetic nephropathy, through both receptor dependant and independent interactions. AGEs elicit their receptor mediated effects via their engagement with numerous receptors and binding proteins which are broadly thought to be either inflammatory (RAGE and AGE-R2) or clearance receptors (AGE-R1, AGE-R3, CD36, Scr-II, FEEL-1 and FEEL-2). Modulation of AGE receptor expression is an important potential therapeutic approach worth consideration as a treatment for diabetic nephropathy and likely applicable to other vascular complications.
 ...
PMID:Interactions between advanced glycation end-products (AGE) and their receptors in the development and progression of diabetic nephropathy - are these receptors valid therapeutic targets. 1914 35