Wada A

References (11)

Title : Lipoprotein Lipase Up-regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice - Teratani_2019_Hepatol.Commun_3_1098
Author(s) : Teratani T , Tomita K , Furuhashi H , Sugihara N , Higashiyama M , Nishikawa M , Irie R , Takajo T , Wada A , Horiuchi K , Inaba K , Hanawa Y , Shibuya N , Okada Y , Kurihara C , Nishii S , Mizoguchi A , Hozumi H , Watanabe C , Komoto S , Nagao S , Yamamoto J , Miura S , Hokari R , Kanai T
Ref : Hepatol Commun , 3 :1098 , 2019
Abstract : Lipoprotein lipase (LPL) plays a central role in incorporating plasma lipids into tissues and regulates lipid metabolism and energy balance in the human body. Conversely, LPL expression is almost absent in normal adult livers. Therefore, its physiological role in the liver remains unknown. We aimed to elucidate the role of LPL in the pathophysiology of nonalcoholic steatohepatitis (NASH), a hepatic manifestation of obesity. Hepatic stellate cell (HSC)-specific LPL-knockout (Lpl(HSC-KO) ) mice, LPL-floxed (Lpl(fl/fl) ) mice, or double-mutant toll-like receptor 4-deficient (Tlr4(-/-) ) Lpl(HSC-KO) mice were fed a high-fat/high-cholesterol diet for 4 weeks to establish the nonalcoholic fatty liver model or an high-fat/high-cholesterol diet for 24 weeks to establish the NASH model. Human samples, derived from patients with nonalcoholic fatty liver disease, were also examined. In human and mouse NASH livers, serum obesity-related factors, such as free fatty acid, leptin, and interleukin-6, dramatically increased the expression of LPL, specifically in HSCs through signal transducer and activator of transcription 3 signaling, as opposed to that in hepatocytes or hepatic macrophages. In the NASH mouse model, liver fibrosis was significantly reduced in Lpl(HSC-KO) mice compared with that in Lpl(fl/fl) mice. Nonenzymatic LPL-mediated cholesterol uptake from serum lipoproteins enhanced the accumulation of free cholesterol in HSCs, which amplified TLR4 signaling, resulting in the activation of HSCs and progression of hepatic fibrosis in NASH. Conclusion: The present study reveals the pathophysiological role of LPL in the liver, and furthermore, clarifies the pathophysiology in which obesity, as a background factor, exacerbates NASH. The LPL-mediated HSC activation pathway could be a promising therapeutic target for treating liver fibrosis in NASH.
ESTHER : Teratani_2019_Hepatol.Commun_3_1098
PubMedSearch : Teratani_2019_Hepatol.Commun_3_1098
PubMedID: 31388630

Title : DPP8 is a novel therapeutic target for multiple myeloma - Sato_2019_Sci.Rep_9_18094
Author(s) : Sato T , Tatekoshi A , Takada K , Iyama S , Kamihara Y , Jawaid P , Rehman MU , Noguchi K , Kondo T , Kajikawa S , Arita K , Wada A , Murakami J , Arai M , Yasuda I , Dang NH , Hatano R , Iwao N , Ohnuma K , Morimoto C
Ref : Sci Rep , 9 :18094 , 2019
Abstract : Dipeptidyl peptidases (DPPs) are proteolytic enzymes that are ideal therapeutic targets in human diseases. Indeed, DPP4 inhibitors are widely used in clinical practice as anti-diabetic agents. In this paper, we show that DPP4 inhibitors also induced cell death in multiple human myeloma cells. Among five DPP4 inhibitors, only two of them, vildagliptin and saxagliptin, exhibited apparent cytotoxic effects on myeloma cell lines, without any difference in suppression of DPP4 activity. As these two DPP4 inhibitors are known to have off-target effects against DPP8/9, we employed the specific DPP8/9 inhibitor 1G244. 1G244 demonstrated anti-myeloma effects on several cell lines and CD138+ cells from patients as well as in murine xenograft model. Through siRNA silencing approach, we further confirmed that DPP8 but not DPP9 is a key molecule in inducing cell death induced by DPP8/9 inhibition. In fact, the expression of DPP8 in CD38+ cells from myeloma patients was higher than that of healthy volunteers. DPP8/9 inhibition induced apoptosis, as evidenced by activated form of PARP, caspases-3 and was suppressed by the pan-caspase inhibitor Z-VAD-FMK. Taken together, these results indicate that DPP8 is a novel therapeutic target for myeloma treatment.
ESTHER : Sato_2019_Sci.Rep_9_18094
PubMedSearch : Sato_2019_Sci.Rep_9_18094
PubMedID: 31792328
Gene_locus related to this paper: human-DPP8

Title : Nav1.7-Ca2+ influx-induced increased phosphorylations of extracellular signal-regulated kinase (ERK) and p38 attenuate tau phosphorylation via glycogen synthase kinase-3beta: priming of Nav1.7 gating by ERK and p38 - Nemoto_2010_Eur.J.Pharmacol_640_20
Author(s) : Nemoto T , Miyazaki S , Kanai T , Maruta T , Satoh S , Yoshikawa N , Yanagita T , Wada A
Ref : European Journal of Pharmacology , 640 :20 , 2010
Abstract : In cultured bovine adrenal chromaffin cells expressing Nav1.7 sodium channel isoform, we previously showed that veratridine-induced Na+ influx via Nav1.7 and the subsequent Ca2+ influx via voltage-dependent calcium channels activated protein kinase C-alpha and Akt, which converged on increasing inhibitory Ser9-phosphorylation of glycogen synthase kinase-3beta, decreasing constitutive Ser396-phosphorylation of tau. Here, veratridine increased constitutive Tyr204-phosphorylation of extracellular signal-regulated kinase-1/-2 (ERK1/ERK2) and constitutive Thr180/Tyr182-dual phosphorylation of p38 by approximately 118% (EC50=2.8 microM). Veratridine-induced increased phosphorylation levels of ERK1/ERK2 and p38 were abolished by tetrodotoxin, extracellular Ca2+ removal, or Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3 ,4-c)-carbazole;Go6976] (protein kinase C-alpha inhibitor). PD98059 (2'-amino-3'-methoxyflavone) (ERK1/ERK2 inhibitor) or SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] (p38 inhibitor) attenuated veratridine-induced increased phosphorylation of glycogen synthase kinase-3beta and decreased phosphorylation of tau by approximately 54% and approximately 56%, as partial blockade by Go6976. Additionally, basal constitutive phosphorylation levels of ERK1/ERK2 and p38 were decreased by PD98059 or SB203580, but not by SB216763 [3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indolo-3-yl)-1H-pyrrole-2,5-dione] (glycogen synthase kinase-3beta inhibitor) or extracellular Ca2+ removal. In this condition, PD98059 or SB203580 (but not SB216763 or extracellular Ca2+ removal) inhibited veratridine-induced 22Na+ influx and 45Ca2+ influx, without changing nicotine-induced 22Na+ influx via nicotinic receptor-associated cation channels and nicotine-induced 45Ca2+ influx via voltage-dependent calcium channels. These results suggest that Nav1.7-Ca2+ influx-protein kinase C-alpha pathway activated ERK1/ERK2 and p38, which increased phosphorylation of glycogen synthase kinase-3beta, decreasing tau phosphorylation. In veratridine-nontreated cells, basal constitutive activities of ERK1/ERK2 and p38 primed Nav1.7 to increase 22Na+ influx.
ESTHER : Nemoto_2010_Eur.J.Pharmacol_640_20
PubMedSearch : Nemoto_2010_Eur.J.Pharmacol_640_20
PubMedID: 20470771

Title : Lysophosphatidic acid-LPA1 receptor-Rho-Rho kinase-induced up-regulation of Nav1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement of 22Na+ influx, 45Ca2+ influx and catecholamine secretion - Maruta_2008_J.Neurochem_105_401
Author(s) : Maruta T , Yanagita T , Matsuo K , Uezono Y , Satoh S , Nemoto T , Yoshikawa N , Kobayashi H , Takasaki M , Wada A
Ref : Journal of Neurochemistry , 105 :401 , 2008
Abstract : In cultured bovine adrenal chromaffin cells, chronic (> or = 24 h) treatment with lysophosphatidic acid (LPA) augmented veratridine-induced 22Na+ influx via Na(v)1.7 by approximately 22% (EC(50) = 1 nmol/L), without changing nicotine-induced 22Na+ influx via nicotinic receptor-associated channel. LPA enhanced veratridine (but not nicotine)-induced 45Ca2+ influx via voltage-dependent calcium channel and catecholamine secretion. LPA shifted concentration-response curve of veratridine for 22Na+ influx upward, without altering the EC(50) of veratridine. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced 22Na+ influx by twofold in non-treated and LPA-treated cells. Whole-cell patch-clamp analysis showed that peak Na+ current amplitude was greater by 39% in LPA (100 nmol/L for 36 h)-treated cells; however, I-V curve and steady-state inactivation/activation curves were comparable between non-treated and LPA-treated cells. LPA treatment (> or = 24 h) increased cell surface [3H]saxitoxin binding by approximately 28%, without altering the K(d) value; the increase was prevented by cycloheximide, actinomycin D, or Ki16425, dioctylglycerol pyrophosphate 8:0 (two inhibitors of LPA(1) and LPA3 receptors), or botulinum toxin C3 (Rho inhibitor), Y27632 (Rho kinase inhibitor), consistent with LPA(1) receptor expression in adrenal chromaffin cells. LPA raised Nav1.7 mRNA level by approximately 37%. Thus, LPA-LPA(1) receptor-Rho/Rho kinase pathway up-regulated cell surface Nav1.7 and Nav1.7 mRNA levels, enhancing veratridine-induced Ca2+ influx and catecholamine secretion.
ESTHER : Maruta_2008_J.Neurochem_105_401
PubMedSearch : Maruta_2008_J.Neurochem_105_401
PubMedID: 18036192

Title : Lithium inhibits function of voltage-dependent sodium channels and catecholamine secretion independent of glycogen synthase kinase-3 in adrenal chromaffin cells - Yanagita_2007_Neuropharmacol_53_881
Author(s) : Yanagita T , Maruta T , Uezono Y , Satoh S , Yoshikawa N , Nemoto T , Kobayashi H , Wada A
Ref : Neuropharmacology , 53 :881 , 2007
Abstract : Lithium has been proven to be effective in the therapy of bipolar disorder, but its mechanism of pharmacological action is not clearly defined. We examined the effects of lithium on voltage-dependent Na(+) channels, nicotinic acetylcholine receptors, and voltage-dependent Ca(2+) channels, as well as catecholamine secretion in cultured bovine adrenal chromaffin cells. Lithium chloride (LiCl) reduced veratridine-induced (22)Na(+) influx in a concentration-dependent manner, even in the presence of ouabain, an inhibitor of Na(+), K(+)-ATPase. Glycogen synthase kinase-3 (GSK-3) inhibitors (SB216763, SB415286 or the GSK-3 inhibitor IX) did not affect veratridine-induced (22)Na(+) influx, as well as inhibitory effect of LiCl on veratridine-induced (22)Na(+) influx. Enhancement of veratridine (site 2 toxin)-induced (22)Na(+) influx caused by alpha-scorpion venom (site 3 toxin), beta-scorpion venom (site 4 toxin), or Ptychodiscus brevis toxin-3 (site 5 toxin), still occurred in the presence of LiCl in the same manner as in the control cells. LiCl also reduced veratridine-induced (45)Ca(2+) influx and catecholamine secretion. In contrast, LiCl (< or = 30 mM) had no effect on nicotine-induced (22)Na(+) influx, (45)Ca(2+) influx and catecholamine secretion, as well as on high K(+)-induced (45)Ca(2+) influx and catecholamine secretion. Chronic treatment with LiCl at 100mM (but not at < or = 30 mM) significantly reduced cell viability in a time-dependent manner. These results suggest that lithium selectively inhibits Na(+) influx thorough Na(+) channels and subsequent Ca(2+) influx and catecholamine secretion, independent of GSK-3 inhibition.
ESTHER : Yanagita_2007_Neuropharmacol_53_881
PubMedSearch : Yanagita_2007_Neuropharmacol_53_881
PubMedID: 17950380

Title : Enhancement of insulin-induced PI3K\/Akt\/GSK-3beta and ERK signaling by neuronal nicotinic receptor\/PKC-alpha\/ERK pathway: up-regulation of IRS-1\/-2 mRNA and protein in adrenal chromaffin cells - Sugano_2006_J.Neurochem_98_20
Author(s) : Sugano T , Yanagita T , Yokoo H , Satoh S , Kobayashi H , Wada A
Ref : Journal of Neurochemistry , 98 :20 , 2006
Abstract : In cultured bovine adrenal chromaffin cells treated with nicotine (10 microm for 24 h), phosphorylation of Akt, glycogen synthase kinase-3beta (GSK-3beta) and extracellular signal-regulated kinase (ERK)1/2 induced by insulin (100 nm for 10 min) was enhanced by approximately 62%, without altering levels of these protein kinases. Nicotine produced time (> 12 h)- and concentration (EC(50) 3.6 and 13 microm)-dependent increases in insulin receptor substrate (IRS)-1 and IRS-2 levels by approximately 125 and 105%, without altering cell surface density of insulin receptors. In these cells, insulin-induced tyrosine phosphorylation of IRS-1/IRS-2 and recruitment of phosphoinositide 3-kinase (PI3K) to IRS-1/IRS-2 were augmented by approximately 63%. The increase in IRS-1/IRS-2 levels induced by nicotine was prevented by nicotinic acetylcholine receptor (nAChR) antagonists, the Ca(2+) chelator 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid tetrakis-acetoxymethyl ester, cycloheximide or actinomycin D. Nicotine increased IRS-1 and IRS-2 mRNA levels by approximately 57 and approximately 50%, and this was prevented by conventional protein kinase C (cPKC) inhibitor Go6976, or ERK kinase inhibitors PD98059 and U0126. Nicotine phosphorylated cPKC-alpha, thereby increasing phosphorylation of ERK1/ERK2, as demonstrated by using Go6976, PD98059 or U0126. Selective activation of cPKC-alpha by thymeleatoxin mimicked these effects of nicotine. Thus, stimulation of nAChRs up-regulated expression of IRS-1/IRS-2 via Ca(2+)-dependent sequential activation of cPKC-alpha and ERK, and enhanced insulin-induced PI3K/Akt/GSK-3beta and ERK signaling pathways.
ESTHER : Sugano_2006_J.Neurochem_98_20
PubMedSearch : Sugano_2006_J.Neurochem_98_20
PubMedID: 16805793

Title : Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells - Kobayashi_2001_Brain.Res.Mol.Brain.Res_87_175
Author(s) : Kobayashi H , Yamamoto R , Kitamura K , Kuwasako K , Minami S , Yanagita T , Shiraishi S , Yokoo H , Eto T , Wada A
Ref : Brain Research Mol Brain Res , 87 :175 , 2001
Abstract : We studied whether a novel proadrenomedullin derived peptide was present and what was its physiological function in cultured bovine adrenal chromaffin cells. We found a high level of proadrenomedullin N-terminal 12 peptide (PAMP-12) which consists of a peptide from 9th amino acid to 20th amino acid of proadrenomedullin N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with catecholamine upon stimulation of nicotinic cholinergic receptors. When PAMP-12 was added in the incubation medium, this peptide inhibited nicotinic receptor-mediated catecholamine release and influx of Na(+) and Ca(2+) into the cells. PAMP-12 did not affect catecholamine release evoked by histamine or by depolarization by high concentration of potassium. PAMP-12 also inhibited synthesis of catecholamines as well as the activation of tyrosine hydroxylase by nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates release and synthesis of catecholamines by acting on nicotinic cholinergic receptors in an autocrine manner in adrenal chromaffin cells.
ESTHER : Kobayashi_2001_Brain.Res.Mol.Brain.Res_87_175
PubMedSearch : Kobayashi_2001_Brain.Res.Mol.Brain.Res_87_175
PubMedID: 11245919

Title : Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx, 45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells - Yokoo_2000_Brain.Res_873_149
Author(s) : Yokoo H , Shiraishi S , Kobayashi H , Yanagita T , Minami S , Yamamoto R , Wada A
Ref : Brain Research , 873 :149 , 2000
Abstract : In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited nicotine-induced 22Na(+) influx via nicotinic receptors (IC(50)=15.5 microM); the suppression by NS-7 was observed in the presence of ouabain, an inhibitor of Na(+),K(+)-ATPase, and was not attenuated upon the washout of NS-7. NS-7 decreased nicotine-induced maximum influx of 22Na(+) without altering the EC(50) value of nicotine. Also, NS-7 diminished nicotine-induced 45Ca(2+) influx via nicotinic receptors and voltage-dependent Ca(2+) channels (IC(50)=14.1 microM) and catecholamine secretion (IC(50)=19.5 microM). These results suggest that NS-7 produces noncompetitive and long-lasting inhibitory effects on neuronal nicotinic receptors in adrenal chromaffin cells, and interferes with the stimulus-secretion coupling.
ESTHER : Yokoo_2000_Brain.Res_873_149
PubMedSearch : Yokoo_2000_Brain.Res_873_149
PubMedID: 10915823

Title : Selective inhibition by riluzole of voltage-dependent sodium channels and catecholamine secretion in adrenal chromaffin cells - Yokoo_1998_Naunyn.Schmiedebergs.Arch.Pharmacol_357_526
Author(s) : Yokoo H , Shiraishi S , Kobayashi H , Yanagita T , Yamamoto R , Wada A
Ref : Naunyn Schmiedebergs Arch Pharmacol , 357 :526 , 1998
Abstract : We examined the effects of riluzole, a neuroprotective drug, on voltage-dependent Na channels, nicotinic receptors, and voltage-dependent Ca channels, as well as catecholamine secretion, in comparison with those of verapamil and nicardipine, in primary cultures of bovine adrenal chromaffin cells. Riluzole inhibited veratridine-induced 22Na influx via voltage-dependent Na channels even in the presence of ouabain, an inhibitor of Na,K-ATPase. Blockade of Na channels by riluzole was concentration-dependent with an IC50 of 5.3 microM. It was associated with a similar concentration-related reduction of veratridine-induced 45Ca influx via voltage-dependent Ca channels, and of catecholamine secretion. Riluzole had no effect on 45Ca influx caused by high K, which directly activates voltage-dependent Ca channels, and on nicotine-induced 22Na influx, which passes through the nicotinic receptors. Verapamil and nicardipine attenuated 22Na influx caused by veratridine or nicotine at the same concentrations as they suppressed high K-induced 45Ca influx. The inhibitory effect of riluzole on veratridine-induced 22Na influx disappeared at high concentrations of veratridine. A potentiation of veratridine (site 2 toxin)-induced 22Na influx caused by alpha-scorpion venom (site 3 toxin), beta-scorpion venom (site 4 toxin), or brevetoxin PbTx-3 (site 5 toxin), occurred in the presence of riluzole in the same manner as in control cells. These results suggest that riluzole binds to the veratridine site in voltage-dependent Na channels. It does not impair the cooperative interaction between the functional peptide segments of Na channels, but selectively inhibits gating of Na channels, thereby reducing Ca influx via Ca channels and catecholamine secretion. In contrast, verapamil and nicardipine suppress Na influx both Na channels and nicotinic receptors.
ESTHER : Yokoo_1998_Naunyn.Schmiedebergs.Arch.Pharmacol_357_526
PubMedSearch : Yokoo_1998_Naunyn.Schmiedebergs.Arch.Pharmacol_357_526
PubMedID: 9650805

Title : Up-regulation of sodium channel subunit mRNAs and their cell surface expression by antiepileptic valproic acid: activation of calcium channel and catecholamine secretion in adrenal chromaffin cells - Yamamoto_1997_J.Neurochem_68_1655
Author(s) : Yamamoto R , Yanagita T , Kobayashi H , Yokoo H , Wada A
Ref : Journal of Neurochemistry , 68 :1655 , 1997
Abstract : Treatment of cultured bovine adrenal chromaffin cells with a therapeutic concentration (0.6 mM) of valproic acid (VPA) for > 24 h caused a time-dependent (t1/2 = 74 h) increase in [3H]saxitoxin binding up to 1.4-fold without altering the KD value; it was prevented by the simultaneous treatment with cycloheximide (an inhibitor of protein synthesis). VPA also raised Na+ channel alpha- and beta 1-subunit mRNA levels 1.4- and 1.7-fold at 24 h, and 1.6- and 1.8-fold at 72 h, respectively. Chronic (but not acute) exposure to VPA enhanced 22Na+ influx caused by various concentrations of veratridine 1.4-2.1-fold, even when assayed in the presence of Na+,K(+)-ATPase inhibitor, but did not change the EC50 value of veratridine. Ptychodiscus brevis toxin-3 allosterically potentiated veratridine-induced 22Na+ influx by approximately 2-fold in VPA-treated cells as in nontreated cells. Long-term treatment with VPA augmented veratridine-induced 45Ca2+ influx via voltage-dependent Ca2+ channels and catecholamine secretion, but had no effect on 45Ca2+ influx and catecholamine secretion caused by high K+ (a direct activation of voltage-dependent Ca2+ channels). Chronic treatment with VPA also enhanced nicotine-induced 22Na+ influx via the nicotinic receptor-ion channel complex 1.2-1.4-fold with little change in the EC50 value of nicotine, thereby increasing the nicotine-induced 45Ca2+ influx via voltage-dependent Ca2+ channels and catecholamine secretion. These results suggest that chronic treatment with VPA up-regulates cell surface expression of Na+ channels via the transcription/translation-dependent mechanisms, and probably of nicotinic receptors, thereby resulting in the enhancement of Ca2+ channel gating and catecholamine secretion.
ESTHER : Yamamoto_1997_J.Neurochem_68_1655
PubMedSearch : Yamamoto_1997_J.Neurochem_68_1655
PubMedID: 9084438

Title : Up-regulation of functional voltage-dependent sodium channels by insulin in cultured bovine adrenal chromaffin cells - Yamamoto_1996_J.Neurochem_67_1401
Author(s) : Yamamoto R , Yanagita T , Kobayashi H , Yuhi T , Yokoo H , Wada A
Ref : Journal of Neurochemistry , 67 :1401 , 1996
Abstract : Treatment of cultured bovine adrenal chromaffin cells with 100 nM insulin raised [3H]saxitoxin ([3H]-STX) binding in a time-dependent manner (t1/2 = 26 h). Insulin (100 nM for 4 days) increased the Bmax of [3H]STX binding by 49% without changing the KD value and also augmented the maximal influx of 22Na+ due to 560 microM veratridine by 39% without altering the EC50 value of veratridine. The stimulatory effect of insulin on 22Na+ influx was concentration-dependent with an EC50 of 3 nM, whereas insulin-like growth factor (IGF)-I had little effect at 1 nM. Ptychodiscus brevis toxin-3 allosterically potentiated veratridine (100 microM)-induced 22Na+ influx by approximately twofold in both insulin-treated cells and untreated cells. Veratridine-induced 45Ca2+ influx via voltage-dependent Ca2+ channels and catecholamine secretion were also enhanced by insulin treatment, whereas insulin did not alter nicotine-induced 22Na+ influx via the nicotinic receptor-ion channel complex and high-K+ (direct activation of voltage-dependent Ca2+ channels)-induced 45Ca2+ influx. Stimulatory effects of insulin on [3H]-STX binding and veratridine-induced 22Na+ influx were nullified by simultaneous treatment with either 5,6-dichlorobenzimidazole riboside, an inhibitor of RNA synthesis, or cycloheximide, an inhibitor of protein synthesis, whereas insulin treatment did not appreciably increase the level of mRNA encoding the Na+ channel alpha-subunit. These results suggest that the binding of insulin to insulin (but not IGF-I) receptors mediates the up-regulation of functional Na+ channel expression at plasma membranes; this up-regulation may be due, at least in part, to the de novo synthesis of an as yet unidentified protein(s).
ESTHER : Yamamoto_1996_J.Neurochem_67_1401
PubMedSearch : Yamamoto_1996_J.Neurochem_67_1401
PubMedID: 8858921