Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Megalin is an endocytic receptor on the apical membranes of proximal tubule cells (PTC) in the kidney, and is involved in the reabsorption and metabolism of various proteins that have been filtered by glomeruli. Patients with diabetes, especially type 2 diabetes, or metabolic syndrome are likely to have elevated serum levels of advanced glycation end products, liver-type fatty acid binding protein, angiotensin II, insulin and leptin, and renal metabolism of these proteins is potentially overloaded. Some of these proteins are themselves nephrotoxic, while others are carriers of nephrotoxic molecules. Megalin is involved in the proximal tubular uptake of these proteins. We hypothesize that megalin-mediated metabolic overload in PTC leads to compensatory cellular hypertrophy and sustained Na+ reabsorption, causing systemic hypertension and glomerular hyperfiltration via tubuloglomerular feedback, and named this as 'protein metabolic overload hypothesis'. Impaired metabolism of bioactive proteins such as angiotensin II and insulin in PTC may enhance hypertrophy of PTC and/or Na+ reabsorption. Sleep apnoea syndrome, a frequent complication of diabetes and metabolic syndrome, may cause renal hypoxia and result in relative overload of protein metabolism in the kidneys. The development of strategies to identify patients with diabetes or metabolic syndrome who are at high risk for renal metabolic overload would allow intensive treatment of these patients in an effort to prevent the development of nephropathy. Further studies on the intracellular molecular signalling associated with megalin-mediated metabolic pathways may lead to the development of novel strategies for the treatment of nephropathies related to diabetes and metabolic syndrome.
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PMID:Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis. 1617 84

Obstructive sleep apnoea (OSA) is associated with insulin resistance and metabolic syndrome. There is evidence that adipocyte-fatty acid binding protein (A-FABP) may be involved in the development of cardiometabolic dysfunction. The present authors hypothesise that A-FABP is upregulated in OSA. A total of 124 males without hypertension, diabetes mellitus, hyperlipidaemia or cardiovascular disease were recruited and underwent polysomnography. Serum A-FABP levels showed significant positive correlations with duration of oxygen desaturation and minimal oxygen saturation, fasting insulin and insulin resistance index by homeostasis model assessment. When subjects were divided into tertiles according to apnoea/hypopnoea index (AHI), serum A-FABP levels were significantly higher in the group with AHI >/=34.4 events.h(-1) than the groups with AHI 13.2-34.4 events.h(-1) or with AHI <13.2 events.h(-1). Serum A-FABP levels were significantly higher in the AHI >/=34.4 group than obesity-matched subjects with AHI <34.4 events.h(-1). Serum adipocyte-fatty acid binding protein levels correlated with obstructive sleep apnoea and insulin resistance, independently of obesity, and were significantly higher in severe obstructive sleep apnoea. Adipocyte-fatty acid binding protein may play a role in obstructive sleep apnoea and metabolic dysfunction.
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PMID:Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance. 1918 13