Defective hepatic nitric oxide action results in HISS-dependent insulin resistance in spontaneously hypertensive rats.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

6 Citations (Scopus)

Abstract

Peripheral insulin sensitivity is dependent on the action of Hepatic Insulin Sensitizing Substance (HISS), in which hepatic NO (HNO) plays an important role. Insulin resistance has been associated with hypertension. NO action is known to be impaired in Spontaneously Hypertensive Rat (SHR) hypertension models. We tested the hypothesis that the HNO pathway is compromised in SHR, resulting in HISS-dependent insulin resistance. Wistar rats (Wis) were the normotensive controls. Insulin sensitivity was evaluated through the Rapid Insulin Sensitivity Test (RIST), a modified euglycemic clamp. A clamp was performed in basal state (control RIST), followed by ipv administration of the NO synthase (NOS) competitive antagonist L-NMMA (0.73 mg/kg) and a RIST post L-NMMA. HISS-dependent insulin sensitivity was assessed by subtracting the RIST post-L-NMMA from the control RIST and is represented as the resultant insulin sensitivity inhibition. In SHR ipv L-NMMA induced 26+/-5% insulin sensitivity inhibition (187.5+/-15.3 mg glucose/kg, n=6; P<0.05), whereas in Wis, ipv L-NMMA induced 53.8+/-5.9% insulin sensitivity inhibition (138.2+/-14.7 mg glucose/kg, n=6, P<0.05), significantly higher than in SHR (P<0.01). Our results suggest that functional HNO is essential to achieve maximal insulin sensitivity and that HNO action is compromised in hypertension, resulting in HISS-dependent insulin resistance.
Original languageUnknown
Title of host publicationPROCEEDINGS OF THE WESTERN PHARMACOLOGY SOCIETY
Pages103-104
Volume47
Publication statusPublished - 1 Jan 2004
Event47th Annual Meeting of the Western-Pharmacology-Society Location: Honolulu, HI Date: JAN 25-30, 2004 -
Duration: 1 Jan 2004 → …

Conference

Conference47th Annual Meeting of the Western-Pharmacology-Society Location: Honolulu, HI Date: JAN 25-30, 2004
Period1/01/04 → …

Cite this

@inproceedings{8578140c2d68429c8d6a567557031814,
title = "Defective hepatic nitric oxide action results in HISS-dependent insulin resistance in spontaneously hypertensive rats.",
abstract = "Peripheral insulin sensitivity is dependent on the action of Hepatic Insulin Sensitizing Substance (HISS), in which hepatic NO (HNO) plays an important role. Insulin resistance has been associated with hypertension. NO action is known to be impaired in Spontaneously Hypertensive Rat (SHR) hypertension models. We tested the hypothesis that the HNO pathway is compromised in SHR, resulting in HISS-dependent insulin resistance. Wistar rats (Wis) were the normotensive controls. Insulin sensitivity was evaluated through the Rapid Insulin Sensitivity Test (RIST), a modified euglycemic clamp. A clamp was performed in basal state (control RIST), followed by ipv administration of the NO synthase (NOS) competitive antagonist L-NMMA (0.73 mg/kg) and a RIST post L-NMMA. HISS-dependent insulin sensitivity was assessed by subtracting the RIST post-L-NMMA from the control RIST and is represented as the resultant insulin sensitivity inhibition. In SHR ipv L-NMMA induced 26+/-5{\%} insulin sensitivity inhibition (187.5+/-15.3 mg glucose/kg, n=6; P<0.05), whereas in Wis, ipv L-NMMA induced 53.8+/-5.9{\%} insulin sensitivity inhibition (138.2+/-14.7 mg glucose/kg, n=6, P<0.05), significantly higher than in SHR (P<0.01). Our results suggest that functional HNO is essential to achieve maximal insulin sensitivity and that HNO action is compromised in hypertension, resulting in HISS-dependent insulin resistance.",
keywords = "&, Pharmacy, Pharmacology",
author = "Ribeiro, {Rog{\'e}rio Jos{\'e} Tavares} and Afonso, {Ricardo Alexandre da Silva Santos} and Macedo, {Maria Paula Borges de Lemos}",
year = "2004",
month = "1",
day = "1",
language = "Unknown",
volume = "47",
pages = "103--104",
booktitle = "PROCEEDINGS OF THE WESTERN PHARMACOLOGY SOCIETY",

}

Ribeiro, RJT, Afonso, RADSS & Macedo, MPBDL 2004, Defective hepatic nitric oxide action results in HISS-dependent insulin resistance in spontaneously hypertensive rats. in PROCEEDINGS OF THE WESTERN PHARMACOLOGY SOCIETY. vol. 47, pp. 103-104, 47th Annual Meeting of the Western-Pharmacology-Society Location: Honolulu, HI Date: JAN 25-30, 2004, 1/01/04.

Defective hepatic nitric oxide action results in HISS-dependent insulin resistance in spontaneously hypertensive rats. / Ribeiro, Rogério José Tavares; Afonso, Ricardo Alexandre da Silva Santos; Macedo, Maria Paula Borges de Lemos.

PROCEEDINGS OF THE WESTERN PHARMACOLOGY SOCIETY. Vol. 47 2004. p. 103-104.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - Defective hepatic nitric oxide action results in HISS-dependent insulin resistance in spontaneously hypertensive rats.

AU - Ribeiro, Rogério José Tavares

AU - Afonso, Ricardo Alexandre da Silva Santos

AU - Macedo, Maria Paula Borges de Lemos

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Peripheral insulin sensitivity is dependent on the action of Hepatic Insulin Sensitizing Substance (HISS), in which hepatic NO (HNO) plays an important role. Insulin resistance has been associated with hypertension. NO action is known to be impaired in Spontaneously Hypertensive Rat (SHR) hypertension models. We tested the hypothesis that the HNO pathway is compromised in SHR, resulting in HISS-dependent insulin resistance. Wistar rats (Wis) were the normotensive controls. Insulin sensitivity was evaluated through the Rapid Insulin Sensitivity Test (RIST), a modified euglycemic clamp. A clamp was performed in basal state (control RIST), followed by ipv administration of the NO synthase (NOS) competitive antagonist L-NMMA (0.73 mg/kg) and a RIST post L-NMMA. HISS-dependent insulin sensitivity was assessed by subtracting the RIST post-L-NMMA from the control RIST and is represented as the resultant insulin sensitivity inhibition. In SHR ipv L-NMMA induced 26+/-5% insulin sensitivity inhibition (187.5+/-15.3 mg glucose/kg, n=6; P<0.05), whereas in Wis, ipv L-NMMA induced 53.8+/-5.9% insulin sensitivity inhibition (138.2+/-14.7 mg glucose/kg, n=6, P<0.05), significantly higher than in SHR (P<0.01). Our results suggest that functional HNO is essential to achieve maximal insulin sensitivity and that HNO action is compromised in hypertension, resulting in HISS-dependent insulin resistance.

AB - Peripheral insulin sensitivity is dependent on the action of Hepatic Insulin Sensitizing Substance (HISS), in which hepatic NO (HNO) plays an important role. Insulin resistance has been associated with hypertension. NO action is known to be impaired in Spontaneously Hypertensive Rat (SHR) hypertension models. We tested the hypothesis that the HNO pathway is compromised in SHR, resulting in HISS-dependent insulin resistance. Wistar rats (Wis) were the normotensive controls. Insulin sensitivity was evaluated through the Rapid Insulin Sensitivity Test (RIST), a modified euglycemic clamp. A clamp was performed in basal state (control RIST), followed by ipv administration of the NO synthase (NOS) competitive antagonist L-NMMA (0.73 mg/kg) and a RIST post L-NMMA. HISS-dependent insulin sensitivity was assessed by subtracting the RIST post-L-NMMA from the control RIST and is represented as the resultant insulin sensitivity inhibition. In SHR ipv L-NMMA induced 26+/-5% insulin sensitivity inhibition (187.5+/-15.3 mg glucose/kg, n=6; P<0.05), whereas in Wis, ipv L-NMMA induced 53.8+/-5.9% insulin sensitivity inhibition (138.2+/-14.7 mg glucose/kg, n=6, P<0.05), significantly higher than in SHR (P<0.01). Our results suggest that functional HNO is essential to achieve maximal insulin sensitivity and that HNO action is compromised in hypertension, resulting in HISS-dependent insulin resistance.

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KW - Pharmacy

KW - Pharmacology

M3 - Conference contribution

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BT - PROCEEDINGS OF THE WESTERN PHARMACOLOGY SOCIETY

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