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Improved Insulin sensitivity with angiotensin receptor neprilysin Inhibition in individuals with obesity and hypertension

Jordan, J. and Stinkens, R. and Jax, T. and Engeli, S. and Blaak, E.E. and May, M. and Havekes, B. and Schindler, C. and Albrecht, D. and Pal, P. and Heise, T. and Goossens, G.H. and Langenickel, T.H. (2017) Improved Insulin sensitivity with angiotensin receptor neprilysin Inhibition in individuals with obesity and hypertension. Clinical Pharmacology and Therapeutics, 101 (2), pp. 254-63. DOI: 10.1002/cpt.455 ISSN 0009-9236

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Abstract

Natriuretic peptide (NP) deficiency and sustained renin-angiotensin system activation are associated with impaired oxida- tive metabolism and predispose to type-2 diabetes. We hypothesized that sacubitril/valsartan (LCZ696), which augments NP through neprilysin inhibition while blocking angiotensin II type-1 (AT1)-receptors, improves insulin sensitivity, lipid mobilization, and oxidation. After 8 weeks of treatment of obese patients with hypertension, sacubitril/valsartan 400 mg q.d., but not amlodipine 10 mg q.d., was associated with a significant increase from baseline in the insulin sensitivity index (hyperinsulinemic-euglycemic clamp), and tended to be higher in patients treated with sacubitril/valsartan compared to amlodipine. Abdominal adipose tissue interstitial glycerol concentrations increased with sacubitril/valsartan, but decreased with amlodipine. Whole-body lipolysis and substrate oxidation did not change with either treatment. Results confirm that sacubitril/valsartan treatment leads to a metabolic benefit in the study population and supports the relevance of neprilysin inhibition along with AT1-receptor blockade in the regulation of human glucose and lipid metabolism.

Item URL in elib:https://elib.dlr.de/118728/
Document Type:Article
Title:Improved Insulin sensitivity with angiotensin receptor neprilysin Inhibition in individuals with obesity and hypertension
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Jordan, J.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Stinkens, R.Department of Human Biology, NetherlandsUNSPECIFIED
Jax, T.Profil, GermanyUNSPECIFIED
Engeli, S.Institute for Clinical Pharmacology, GermanyUNSPECIFIED
Blaak, E.E.Department of Human Biology, NetherlandsUNSPECIFIED
May, M.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Havekes, B.Department of Internal Medicine, NetherlandsUNSPECIFIED
Schindler, C.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Albrecht, D.Translational Medicine Novartis, SwitzerlandUNSPECIFIED
Pal, P.Biostatistical Sciences, Novartis, IndiaUNSPECIFIED
Heise, T.Profil, GermanyUNSPECIFIED
Goossens, G.H.Department of Human Biology, NetherlandsUNSPECIFIED
Langenickel, T.H.Translational Medicine, Novartis, SwitzerlandUNSPECIFIED
Date:2017
Journal or Publication Title:Clinical Pharmacology and Therapeutics
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:101
DOI :10.1002/cpt.455
Page Range:pp. 254-63
ISSN:0009-9236
Status:Published
Keywords:Insulin, Obesity and Hypertension,
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Projekt :envihab
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Leitungsbereich ME
Deposited By: Jackman, Sabine
Deposited On:06 Feb 2018 11:05
Last Modified:06 Feb 2018 11:05

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