Journal article
P-506: Renal sympathoactivation to insulin is mediated by melanocortin-4 receptors
American journal of hypertension, Vol.16(S1), pp.221A-221A
05/2003
DOI: 10.1016/S0895-7061(03)00679-4
Abstract
Insulin acts in the central nervous system to increase sympathetic nerve activity. The pathways by which insulin affects sympathetic nerve traffic have not been reported. Recently, insulin was shown to stimulate expression of the a-MSH precursor pro-opiomelanocortin in hypothalamic neurons and blockade of central melanocortin-4 receptors (MC-4R) inhibit the feeding response to insulin. We examined the role of MC-4R in mediating the sympathoexcitatory effects of insulin. We compared the effects of intracerebroventricular (ICV) administration of insulin in MC-4R knockout and wild-type mice (C57BL/6J). The effects of ICV administration of MC-4R agonist (MTII), insulin or corticotrophin releasing factor (CRF) were recorded during 4 hours under anesthesia (Xylaxine/Ketamine). As expected, ICV administration of MT II (2 mcg) increased RSNA in wild-type mice by 299±48% (n=6, P<0.001), but not in the homozygous MC-4R knockout mice (n=5). The RSNA response to MTII in the heterozygous MC4R mutant mice was intermediate between the wild type and homozygous mutant sibs (153±31%, n=9, P<0.001). Insulin (20 mcU) induced a significant rise in RSNA in the wild-type mice (190±30%, n=7, P<0.001), but not in the homozygous MC4-R knockout mice (4±11%, n=6). The RSNA response to insulin in the heterozygous MC4R mutant mice was also intermediate between the wild type and homozygous MC4R mutant mice (95±22%, n=11, P<0.01). However, renal sympathoactivation induced by CRF (5 mcg) was comparable in wild type, heterozygous and homozygous MC4-R knockout mice (209±52, 200±57 and 250±52%, respectively, P=0.78). Our data demonstrate that the rise in renal sympathetic nerve outflow induced by insulin is mediated by the melanocortin-4 receptors because the sympathoexcitatory effect of insulin was absent in homozygous mice and attenuated in the heterozygous melanocortin-4 receptor knockout mice.
Details
- Title: Subtitle
- P-506: Renal sympathoactivation to insulin is mediated by melanocortin-4 receptors
- Creators
- Kamal Rahmouni - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USADonald A Morgan - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USAWilliam G Haynes - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- American journal of hypertension, Vol.16(S1), pp.221A-221A
- DOI
- 10.1016/S0895-7061(03)00679-4
- ISSN
- 0895-7061
- eISSN
- 1879-1905
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 05/2003
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984072093202771
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