7 Citations (Scopus)

Abstract

Objective: Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic-dependent pathway is diminished in OZR, resulting in IR. Research Methods and Procedures: Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post-atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, L-NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic-dependent IS was assessed by subtracting the response after atropine or L-NMMA from the basal response. Results: In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 +/- 14.2; LZR, 289.2 +/- 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 +/- 8.0%; LZR, 40.1 +/- 6.5%). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 +/- 1.6; LZR, 287.4 +/- 22.7 mg glucose/kg bw; p < 0.001). L-NMMA induced IS inhibition in both groups (OZR, 48.3 +/- 6.6%; LZR, 46.4 +/- 4.1%), similar to that after atropine. Discussion: We show that the IR in OZR is due to similar impairment of both hepatic-dependent and -independent components of insulin action, suggesting the existence of a defect common to both pathways.
Original languageUnknown
Pages (from-to)314-321
JournalObesity
Volume15
Issue number2
DOIs
Publication statusPublished - 1 Jan 2007

Cite this

@article{3c0ebe19a482445ab81ec89ff0a616d3,
title = "Hepatic-dependent and -independent insulin actions are impaired in the obese Zucker rat model",
abstract = "Objective: Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic-dependent pathway is diminished in OZR, resulting in IR. Research Methods and Procedures: Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post-atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, L-NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic-dependent IS was assessed by subtracting the response after atropine or L-NMMA from the basal response. Results: In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 +/- 14.2; LZR, 289.2 +/- 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 +/- 8.0{\%}; LZR, 40.1 +/- 6.5{\%}). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 +/- 1.6; LZR, 287.4 +/- 22.7 mg glucose/kg bw; p < 0.001). L-NMMA induced IS inhibition in both groups (OZR, 48.3 +/- 6.6{\%}; LZR, 46.4 +/- 4.1{\%}), similar to that after atropine. Discussion: We show that the IR in OZR is due to similar impairment of both hepatic-dependent and -independent components of insulin action, suggesting the existence of a defect common to both pathways.",
keywords = "BLOCKADE, EXPRESSION, SKELETAL-MUSCLE, GLUCOSE-TRANSPORT, NITRIC-OXIDE, SENSITIVITY TEST RIST, LEPTIN, ACTIVATION, RESISTANCE, PATHWAY",
author = "Macedo, {Maria Paula Borges de Lemos} and Afonso, {Ricardo Alexandre da Silva Santos} and Patarr{\~a}o, {Rita Susana Franco das Neves} and Ribeiro, {Rog{\'e}rio Jos{\'e} Tavares} and Fernandes, {Ana Barbosa de Matos Abreu}",
year = "2007",
month = "1",
day = "1",
doi = "10.1038/oby.2007.524",
language = "Unknown",
volume = "15",
pages = "314--321",
journal = "Obesity",
issn = "1071-7323",
publisher = "The North American Association for the Study of",
number = "2",

}

TY - JOUR

T1 - Hepatic-dependent and -independent insulin actions are impaired in the obese Zucker rat model

AU - Macedo, Maria Paula Borges de Lemos

AU - Afonso, Ricardo Alexandre da Silva Santos

AU - Patarrão, Rita Susana Franco das Neves

AU - Ribeiro, Rogério José Tavares

AU - Fernandes, Ana Barbosa de Matos Abreu

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Objective: Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic-dependent pathway is diminished in OZR, resulting in IR. Research Methods and Procedures: Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post-atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, L-NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic-dependent IS was assessed by subtracting the response after atropine or L-NMMA from the basal response. Results: In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 +/- 14.2; LZR, 289.2 +/- 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 +/- 8.0%; LZR, 40.1 +/- 6.5%). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 +/- 1.6; LZR, 287.4 +/- 22.7 mg glucose/kg bw; p < 0.001). L-NMMA induced IS inhibition in both groups (OZR, 48.3 +/- 6.6%; LZR, 46.4 +/- 4.1%), similar to that after atropine. Discussion: We show that the IR in OZR is due to similar impairment of both hepatic-dependent and -independent components of insulin action, suggesting the existence of a defect common to both pathways.

AB - Objective: Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic-dependent pathway is diminished in OZR, resulting in IR. Research Methods and Procedures: Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post-atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, L-NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic-dependent IS was assessed by subtracting the response after atropine or L-NMMA from the basal response. Results: In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 +/- 14.2; LZR, 289.2 +/- 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 +/- 8.0%; LZR, 40.1 +/- 6.5%). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 +/- 1.6; LZR, 287.4 +/- 22.7 mg glucose/kg bw; p < 0.001). L-NMMA induced IS inhibition in both groups (OZR, 48.3 +/- 6.6%; LZR, 46.4 +/- 4.1%), similar to that after atropine. Discussion: We show that the IR in OZR is due to similar impairment of both hepatic-dependent and -independent components of insulin action, suggesting the existence of a defect common to both pathways.

KW - BLOCKADE

KW - EXPRESSION

KW - SKELETAL-MUSCLE

KW - GLUCOSE-TRANSPORT

KW - NITRIC-OXIDE

KW - SENSITIVITY TEST RIST

KW - LEPTIN

KW - ACTIVATION

KW - RESISTANCE

KW - PATHWAY

U2 - 10.1038/oby.2007.524

DO - 10.1038/oby.2007.524

M3 - Article

VL - 15

SP - 314

EP - 321

JO - Obesity

JF - Obesity

SN - 1071-7323

IS - 2

ER -