Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

WNK-oxidative stress-responsive 1 (OSR1) /STE20/SPS1-related proline-alanine-rich protein kinase(SPAK)-SLC12A transporters cascade regulates blood pressure through NaCl reabsorption in kidney and vasoconstriction. Furthermore, we recently reported that this cascade is positively regulated by insulin, which may contribute to hypertension in patients with hyperinsulinemia. Therefore, drugs that inhibit this signal cascade could become new antihypertensive drugs that have dual effects as a diuretic and vasodilator and be particularly beneficial for patients with hyperinsulinemia such as metabolic syndrome and obesity. In this review, we provide an overview about the current understanding about WNK-SPAK-SLC12A signal cascade and show some prospects for drug discovery that blocks this signal cascade.
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PMID:[WNK-SPAK-SLC12A signal cascade is a new therapeutic target for hypertension]. 2639 27

The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.
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PMID:Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity. 2906 61