Hypertension and insulin resistance

Role of peroxisome proliferator- activated receptor γ

Hiroshi Itoh, Doi Kentaro, Tokuji Tanaka, Yasutomo Fukunaga, Kiminori Hosoda, Gen Inoue, Haruhiko Nishimura, Yasunao Yoshimasa, Yukio Yamori, Kazuwa Nakao

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ. 3. cDNA of rat PPARγ1 and γ2 were cloned and gene regulation of PPARγ in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPARγ mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-α, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPARγ expression. 5. Thiazolidinediones dose-dependently recovered TNF-α-induced down-regulation of PPARγ mRNA expression. 6. The modulation of PPARγ expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPARγ gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.

Original languageEnglish
Pages (from-to)558-560
Number of pages3
JournalClinical and Experimental Pharmacology and Physiology
Volume26
Issue number7
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Thiazolidinediones
Peroxisome Proliferator-Activated Receptors
Insulin Resistance
Hypertension
Endothelium
Adipocytes
Endothelial Cells
Tumor Necrosis Factor-alpha
Obesity
C-Type Natriuretic Peptide
Messenger RNA
Natriuretic Peptides
Peptides
Vascular System Injuries
Endothelins
Cytoplasmic and Nuclear Receptors
Hyperlipidemias
Hypoglycemic Agents
Type 2 Diabetes Mellitus
Hydrogen Peroxide

Keywords

  • Adipocytes
  • Endothelial cells
  • Endothelin
  • Insulin resistance
  • Natriuretic peptides
  • Oxidative stress
  • Peroxisome proliferator-activated receptor γ
  • Risk factor
  • Syndrome X
  • Thiazolidinediones

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Hypertension and insulin resistance : Role of peroxisome proliferator- activated receptor γ. / Itoh, Hiroshi; Kentaro, Doi; Tanaka, Tokuji; Fukunaga, Yasutomo; Hosoda, Kiminori; Inoue, Gen; Nishimura, Haruhiko; Yoshimasa, Yasunao; Yamori, Yukio; Nakao, Kazuwa.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 26, No. 7, 1999, p. 558-560.

Research output: Contribution to journalArticle

Itoh, H, Kentaro, D, Tanaka, T, Fukunaga, Y, Hosoda, K, Inoue, G, Nishimura, H, Yoshimasa, Y, Yamori, Y & Nakao, K 1999, 'Hypertension and insulin resistance: Role of peroxisome proliferator- activated receptor γ', Clinical and Experimental Pharmacology and Physiology, vol. 26, no. 7, pp. 558-560. https://doi.org/10.1046/j.1440-1681.1999.03082.x
Itoh, Hiroshi ; Kentaro, Doi ; Tanaka, Tokuji ; Fukunaga, Yasutomo ; Hosoda, Kiminori ; Inoue, Gen ; Nishimura, Haruhiko ; Yoshimasa, Yasunao ; Yamori, Yukio ; Nakao, Kazuwa. / Hypertension and insulin resistance : Role of peroxisome proliferator- activated receptor γ. In: Clinical and Experimental Pharmacology and Physiology. 1999 ; Vol. 26, No. 7. pp. 558-560.
@article{76edf9e388414acfaf879e16d3331294,
title = "Hypertension and insulin resistance: Role of peroxisome proliferator- activated receptor γ",
abstract = "1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ. 3. cDNA of rat PPARγ1 and γ2 were cloned and gene regulation of PPARγ in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPARγ mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-α, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPARγ expression. 5. Thiazolidinediones dose-dependently recovered TNF-α-induced down-regulation of PPARγ mRNA expression. 6. The modulation of PPARγ expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPARγ gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.",
keywords = "Adipocytes, Endothelial cells, Endothelin, Insulin resistance, Natriuretic peptides, Oxidative stress, Peroxisome proliferator-activated receptor γ, Risk factor, Syndrome X, Thiazolidinediones",
author = "Hiroshi Itoh and Doi Kentaro and Tokuji Tanaka and Yasutomo Fukunaga and Kiminori Hosoda and Gen Inoue and Haruhiko Nishimura and Yasunao Yoshimasa and Yukio Yamori and Kazuwa Nakao",
year = "1999",
doi = "10.1046/j.1440-1681.1999.03082.x",
language = "English",
volume = "26",
pages = "558--560",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Hypertension and insulin resistance

T2 - Role of peroxisome proliferator- activated receptor γ

AU - Itoh, Hiroshi

AU - Kentaro, Doi

AU - Tanaka, Tokuji

AU - Fukunaga, Yasutomo

AU - Hosoda, Kiminori

AU - Inoue, Gen

AU - Nishimura, Haruhiko

AU - Yoshimasa, Yasunao

AU - Yamori, Yukio

AU - Nakao, Kazuwa

PY - 1999

Y1 - 1999

N2 - 1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ. 3. cDNA of rat PPARγ1 and γ2 were cloned and gene regulation of PPARγ in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPARγ mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-α, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPARγ expression. 5. Thiazolidinediones dose-dependently recovered TNF-α-induced down-regulation of PPARγ mRNA expression. 6. The modulation of PPARγ expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPARγ gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.

AB - 1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR)γ. 3. cDNA of rat PPARγ1 and γ2 were cloned and gene regulation of PPARγ in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPARγ mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-α, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPARγ expression. 5. Thiazolidinediones dose-dependently recovered TNF-α-induced down-regulation of PPARγ mRNA expression. 6. The modulation of PPARγ expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPARγ gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.

KW - Adipocytes

KW - Endothelial cells

KW - Endothelin

KW - Insulin resistance

KW - Natriuretic peptides

KW - Oxidative stress

KW - Peroxisome proliferator-activated receptor γ

KW - Risk factor

KW - Syndrome X

KW - Thiazolidinediones

UR - http://www.scopus.com/inward/record.url?scp=0032993595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032993595&partnerID=8YFLogxK

U2 - 10.1046/j.1440-1681.1999.03082.x

DO - 10.1046/j.1440-1681.1999.03082.x

M3 - Article

VL - 26

SP - 558

EP - 560

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 7

ER -