Identification of bona fide alternative renin transcripts expressed along cortical tubules and potential roles in promoting insulin resistance in vivo without significant plasma renin activity elevation.
Renin belongs to a family of aspartyl proteases and is the rate-limiting enzyme in the synthesis of the potent vasoactive peptide angiotensin II. Processing of renal renin has been extensively investigated in juxtaglomerular granular cells, in which prorenin and active renin are present in secretory...
| Published in: | Hypertension (0194911X) Vol. 64; no. 1; pp. 125 - 134 |
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| Main Authors: | , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
Lippincott Williams & Wilkins
Jul2014
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107855689&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 107855689 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0194911X 1FX jtl: Hypertension (0194911X) issn: 0194911X maglogo: N pubinfo: dt: Jul2014 vid: 64 iid: 1 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 107855689 NLM24777979 2012614495 10.1161/HYPERTENSIONAHA.114.03394 NLM24777979 107855689 ppf: 125 ppct: 9 formats: tig: atl: Identification of bona fide alternative renin transcripts expressed along cortical tubules and potential roles in promoting insulin resistance in vivo without significant plasma renin activity elevation. aug: au: Ishigami, Tomoaki Kino, Tabito Chen, Lin Minegishi, Shintaro Araki, Naomi Umemura, Masanari Abe, Kaito Sasaki, Rie Yamana, Hisako Umemura, Satoshi affil: From the Department of Medical Science and Cardio-Renal Medicine, Yokohama City University, Graduate School of Medicine, Yokohama, Japan. tommmish@hotmail.com. sug: subj: Insulin Resistance Kidney Tubules Metabolism Kidney Metabolism Renin Adrenal Glands Metabolism Animal Studies Mice Renin Blood Renin Metabolism Renin-Angiotensin System Physiology ab: Renin belongs to a family of aspartyl proteases and is the rate-limiting enzyme in the synthesis of the potent vasoactive peptide angiotensin II. Processing of renal renin has been extensively investigated in juxtaglomerular granular cells, in which prorenin and active renin are present in secretory condensed granules. Previous studies demonstrated alternative renin transcription in rat adrenal glands. Different studies reported novel intracellular forms of renin deduced from novel 5' variants derived from renin mRNA in both mice and humans. Comprehensive detailed studies in genetically engineered mice showed that both a secreted and an intracellular form of renin plays divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system; however, the presence, regulation, and functions of these renin isoforms in kidney and adrenal gland are not fully understood in mice. To investigate the characteristics of renin isoforms in mice, we performed a systematic inventory of renin transcripts of mice with and without a duplication of the renin gene alternatively from previous studies. We discovered a novel isoform of renin of the Ren2 gene, which conserved functionally important residues of the prosegment and incomplete isoforms of the Ren1C/D gene lacking a pre-pro segment. In situ hybridization assays revealed alternative renin isoforms expressed along cortical tubules. Newly generated transgenic mice with systemic overexpression of alternative renin transcript showed enhanced local angiotensin II generation without elevation of plasma renin activity and systemic insulin resistance in vivo, providing new pathophysiological insights into insulin resistance exaggerated by bona fide renin isoform. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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