Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) is a novel adipocytokine with important metabolic effects. It is physiologically released from adipose tissue and circulates in serum as a hexamer and larger multimeric structure of high molecular weight. Serum level of the protein correlates with systemic insulin sensitivity. Recently adiponectin receptors AdipoR1 and AdipoR2 have been discovered by expression cloning. AdipoR1 is abundantly expressed in skeletal muscles, whereas AdipoR2 is predominantly expressed in the liver. Marked expression of mRNA for AdipoR1 and AdipoR2 has been lately reported in pancreatic beta cells. Both of the receptors activate AMPK and PPAR alpha metabolic pathways leading to an increase in fatty acid oxidation, glucose uptake and a decreased rate of gluconeogenesis, thus enhancing insulin sensitivity. Moreover effects of adiponectin mimic many metabolic actions of insulin such as augmenting blood flow and glucose disposal in NO-dependent manner. The precise mechanism of regulation of plasma adiponectin level is unknown. Recently the mechanism of transcriptional activation of adiponectin gene via PPAR gamma was described. Its level seems to be decreased by TNFalfa and beta-adrenergic agonists. Furthermore there is increasing evidence that some genetic variants in the adiponectin gene may be associated with its ethnical differences in level as well as its likely clinical consequences. Hipoadiponectynemia is associated with obesity, metabolic syndrome, diabetes type 2, cardiovascular disease, lipodystrophy in AIDS. In patients with chronic renal failure, anorexia nervosa plasma adlponectin level is increased. Weight loss and therapy with thlazolidinediones are proved to enhance endogenous adlponectin production in humans. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and antiatherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, especially in individuals with low plasma levels of adiponectin.
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PMID:[Adiponectin--adipocytokine with a broad clinical spectrum]. 1523 Jan 53

Ghrelin is a brain-gut peptide that was discovered through reverse pharmacology and was first isolated from extracts of porcine stomach. Ghrelin binds to growth hormone secretagogue receptor (GHS-R) and is acylated on its serine 3 residue by ghrelin O-acyltransferase (GOAT). Several important biological functions of ghrelin have been identified, which include its growth hormone-releasing and appetite-inducing effects. Ghrelin exerts its central orexigenic effect mainly by acting on the hypothalamic arcuate nucleus via the activation of the GHS-R. Peripherally ghrelin has multiple metabolic effects which include promoting gluconeogenesis and fat deposition. These effects together with the increased food intake lead to an overall body weight gain. AMP-activated protein kinase, which is a key enzyme in energy homeostasis, has been shown to mediate the central and peripheral metabolic effects of ghrelin. The hypothalamic fatty acid pathway, hypothalamic mitochondrial respiration and uncoupling protein 2 have all been shown to act as the downstream targets of AMPK in mediating the orexigenic effects of ghrelin. Abnormal levels of ghrelin are associated with several metabolic conditions such as obesity, type 2 diabetes, Prader-Willi syndrome and anorexia nervosa. The ghrelin/GOAT/GHS-R system is now recognised as a potential target for the development of anti-obesity treatment.
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PMID:The ghrelin/GOAT/GHS-R system and energy metabolism. 2134 May 83