Hepatic glutathione and nitric oxide are critical for hepatic insulin-sensitizing substance action

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 +/- 2.1% compared with control (from 287.3 +/- 18.1 to 155.3 +/- 10.1 mg glucose/ kg, P < 0.05). Insulin sensitivity was restored to 321.7 +/- 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal. sodium nitroprusside (20 mnol.kg(-1).min(-1)), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor 1-buthionine-[S,]sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1%. Insulin sensitivity after L-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by L-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.
Original languageUnknown
Pages (from-to)G588-G594
JournalAmerican Journal Of Physiology-Gastrointestinal And Liver Physiology
Volume284
Issue number4
DOIs
Publication statusPublished - 1 Jan 2003

Cite this

@article{7fae26fa4de749a6ac639e4693ff8c69,
title = "Hepatic glutathione and nitric oxide are critical for hepatic insulin-sensitizing substance action",
abstract = "We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 +/- 2.1{\%} compared with control (from 287.3 +/- 18.1 to 155.3 +/- 10.1 mg glucose/ kg, P < 0.05). Insulin sensitivity was restored to 321.7 +/- 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal. sodium nitroprusside (20 mnol.kg(-1).min(-1)), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor 1-buthionine-[S,]sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1{\%}. Insulin sensitivity after L-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by L-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.",
keywords = "hepatic nitric oxide synthase, AFFECTS GLUCOSE-HOMEOSTASIS, 3T3-L1 ADIPOCYTES, DEPENDENT DIABETES-MELLITUS, SOLUBLE GUANYLYL CYCLASE, CYCLIC-GMP, hepatic parasympathetic nerves, PROTEIN-KINASE B, type 2 diabetes, GLUT4 TRANSLOCATION, HEALTHY-SUBJECTS, S-NITROSOGLUTATHIONE, OXIDATIVE STRESS",
author = "Afonso, {Ricardo Alexandre da Silva Santos} and Guarino, {Maria Pedro Sucena} and Macedo, {Maria Paula Borges de Lemos} and Raposo, {Jo{\~a}o Filipe Cancela dos Santos}",
year = "2003",
month = "1",
day = "1",
doi = "10.1152/ajpgi.00423.2002",
language = "Unknown",
volume = "284",
pages = "G588--G594",
journal = "American Journal Of Physiology-Gastrointestinal And Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Hepatic glutathione and nitric oxide are critical for hepatic insulin-sensitizing substance action

AU - Afonso, Ricardo Alexandre da Silva Santos

AU - Guarino, Maria Pedro Sucena

AU - Macedo, Maria Paula Borges de Lemos

AU - Raposo, João Filipe Cancela dos Santos

PY - 2003/1/1

Y1 - 2003/1/1

N2 - We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 +/- 2.1% compared with control (from 287.3 +/- 18.1 to 155.3 +/- 10.1 mg glucose/ kg, P < 0.05). Insulin sensitivity was restored to 321.7 +/- 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal. sodium nitroprusside (20 mnol.kg(-1).min(-1)), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor 1-buthionine-[S,]sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1%. Insulin sensitivity after L-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by L-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.

AB - We tested the hypothesis that hepatic nitric oxide (NO) and glutathione (GSH) are involved in the synthesis of a putative hormone referred to as hepatic insulin-sensitizing substance HISS. Insulin action was assessed in Wistar rats using the rapid insulin sensitivity test (RIST). Blockade of hepatic NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME, 1.0 mg/kg intraportal) decreased insulin sensitivity by 45.1 +/- 2.1% compared with control (from 287.3 +/- 18.1 to 155.3 +/- 10.1 mg glucose/ kg, P < 0.05). Insulin sensitivity was restored to 321.7 +/- 44.7 mg glucose/kg after administration of an NO donor, intraportal SIN-1 (5 mg/kg), which promotes GSH nitrosation, but not after intraportal. sodium nitroprusside (20 mnol.kg(-1).min(-1)), which does not nitrosate GSH. We depleted hepatic GSH using the GSH synthesis inhibitor 1-buthionine-[S,]sulfoximine (BSO, 2 mmol/kg body wt ip for 20 days), which reduced insulin sensitivity by 39.1%. Insulin sensitivity after L-NAME was not significantly different between BSO- and sham-treated animals. SIN-1 did not reverse the insulin resistance induced by L-NAME in the BSO-treated group. These results support our hypothesis that NO and GSH are essential for insulin action.

KW - hepatic nitric oxide synthase

KW - AFFECTS GLUCOSE-HOMEOSTASIS

KW - 3T3-L1 ADIPOCYTES

KW - DEPENDENT DIABETES-MELLITUS

KW - SOLUBLE GUANYLYL CYCLASE

KW - CYCLIC-GMP

KW - hepatic parasympathetic nerves

KW - PROTEIN-KINASE B

KW - type 2 diabetes

KW - GLUT4 TRANSLOCATION

KW - HEALTHY-SUBJECTS

KW - S-NITROSOGLUTATHIONE

KW - OXIDATIVE STRESS

U2 - 10.1152/ajpgi.00423.2002

DO - 10.1152/ajpgi.00423.2002

M3 - Article

VL - 284

SP - G588-G594

JO - American Journal Of Physiology-Gastrointestinal And Liver Physiology

JF - American Journal Of Physiology-Gastrointestinal And Liver Physiology

SN - 0193-1857

IS - 4

ER -