Mechanisms of Insulin Resistance Leading to Hypertension: What We Can Learn from Experimental Models

The purpose of this article is to summarize the current understanding of the cellular mechanisms of insulin resistance in rat models of arterial hypertension in which decreased sensitivity to insulin occurs. In the first part of the article, we will review briefly the mechanisms of insulin action and the abnormalities of these mechanisms in conditions different from hypertension. In the second part, we will delineate the experimental evidence of abnormal insulin action in hypertensive rats and propose a rationale hypothesis that links insulin resistance with salt-sensitivity and hypertension.

• Publication year

  1997

• Venue

  Journal of Investigative Medicine

• Publication date

  1997-06-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1177/108155899704500503PMID 9249996
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Control by insulin of sodium potassium and water excretion by the isolated dog kidney

  2004cited by this paper
• Relationship between glucose tolerance, insulin secretion, and insulin action in non-obese individuals with varying degrees of glucose tolerance

  2004cited by this paper
• Abnormalities of insulin receptors in spontaneously hypertensive rats.

  1996cited by this paper
• Glycogen synthase activity in two rat models of hypertension.

  1995cited by this paper
• [Detection of mutation in insulin receptor gene in patients with essential hypertension].

  1995cited by this paper
• Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart.

  1995cited by this paper
• Insulin Resistance, Hyperinsulinemia, and Hypertension: Causes, Consequences, or Merely Correlations?

  1995cited by this paper
• Genetic Factors Determine the Blood Pressure Response to Insulin Resistance and Hyperinsulinemia: A Call to Refocus the Insulin Hypothesis of Hypertension

  1995cited by this paper
• Pathophysiology of insulin resistance in human disease.

  1995cited by this paper
• Insulin receptor gene polymorphism and hyperinsulinemia in hypertensive patients.

  1995cited by this paper
• Effects of low sodium diet and unilateral nephrectomy on the development of carbohydrate-induced hypertension.

  1995cited by this paper
• Antihypertensive effects of metformin in fructose-fed hyperinsulinemic, hypertensive rats.

  1994cited by this paper
• Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN-2)27 rats.

  1994cited by this paper
• Vanadyl sulfate prevents fructose-induced hyperinsulinemia and hypertension in rats.

  1994cited by this paper
• In situ characterization of renal insulin receptors in the rat.

  1994cited by this paper
• The relationship of sodium sensitivity to insulin resistance.

  1994cited by this paper
• Metabolic Effects of Troglitazone on Fructose-Induced Insulin Resistance in the Rat

  1994cited by this paper
• Insertion variant in intron 9, but not microsatellite in intron 2, of the insulin receptor gene is associated with essential hypertension

  1994cited by this paper
• Regulation of hepatic insulin receptor tyrosine kinase in rat models of mild insulin resistance.

  1993cited by this paper
• Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance.

  1993cited by this paper
• Cellular insulin action and insulin resistance.

  1993cited by this paper
• Short report: Insertion variant in intron 9, but not microsatellite in intron 2, of the insulin receptor gene is associated with essential hypertension

  1993cited by this paper
• Insulin resistance in the conscious spontaneously hypertensive rat: euglycemic hyperinsulinemic clamp study.

  1993cited by this paper
• Insulin resistance in offspring of hypertensive parents.

  1993cited by this paper
• Genetics of insulin action.

  1993cited by this paper
• Insulin Resistance and Insulin Secretion Are Determinants of Oral Glucose Tolerance in Normal Individuals

  1993cited by this paper
• Sucrose does not raise blood pressure in rats maintained on a low salt intake.

  1993cited by this paper
• Hyperinsulinemia, insulin resistance, and hyperglycemia: contributing factors in the pathogenesis of hypertension and atherosclerosis.

  1993cited by this paper
• Expression of the insulin receptor gene in liver and kidney of rats with genetic hypertension

  1993cited by this paper
• Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.

  1992cited by this paper
• Fasting serum insulin levels in essential hypertension. A meta-analysis.

  1992cited by this paper
• Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension.

  1992cited by this paper
• Insulin resistance in spontaneously hypertensive rats but not in deoxycorticosterone-salt or renal vascular hypertension

  1992cited by this paper
• Increased insulin sensitivity in the high sodium one-kidney, one figure-8 hypertensive rat.

  1992cited by this paper
• Hypertension without peripheral insulin resistance in spontaneously hypertensive rats.

  1992cited by this paper
• Renal vascular hypertension does not lead to hyperinsulinemia in Sprague-Dawley rats.

  1992influential reference
• Insulin resistance in secondary hypertension.

  1992cited by this paper
• Tissue-Specific Regulation of Insulin Receptor mRNA Levels in Rats With STZ-Induced Diabetes Mellitus

  1992cited by this paper
• Effects of insulin on diacylglycerol/protein kinase-C signalling and glucose transport in rat skeletal muscles in vivo and in vitro.

  1992cited by this paper
• Mutations in the insulin receptor gene.

  1992cited by this paper
• Urine sodium excretion in response to an oral glucose tolerance test in obese and nonobese adolescents.

  1992cited by this paper
• Effect of Insulin Therapy on Blood Pressure in NIDDM Patients With Secondary Failure

  1992cited by this paper
• Normal insulin receptor tyrosine kinase activity and glucose transporter (GLUT 4) levels in the skeletal muscle of hyperinsulinaemic hypertensive rats

  1992cited by this paper
• Expression and function of IRS-1 in insulin signal transmission.

  1992cited by this paper
• Insulin stimulation of phosphatidylinositol 3-kinase activity and association with insulin receptor substrate 1 in liver and muscle of the intact rat.

  1992cited by this paper
• Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats.

  1992cited by this paper
• Effects of insulin and phorbol esters on subcellular distribution of protein kinase C isoforms in rat adipocytes.

  1992cited by this paper
• Insulin resistance--mechanisms, syndromes, and implications.

  1991cited by this paper
• Insulin Resistance, Hyperinsulinemia, Hypertriglyceridemia, and Hypertension: Parallels Between Human Disease and Rodent Models

  1991cited by this paper
• Insulin resistance and blood pressure in Dahl rats and in one-kidney, one-clip hypertensive rats.

  1991cited by this paper
• Evaluation of insulin-induced changes in the renal response to furosemide in normal subjects.

  1991cited by this paper
• Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease

  1991cited by this paper
• Altered expression of insulin receptor types A and B in the skeletal muscle of non-insulin-dependent diabetes mellitus patients.

  1991cited by this paper
• Insulin receptor concentration and gene expression are modulated by sodium intake in the rat kidney.

  1991cited by this paper
• Newly Identified Pancreatic Protein Islet Amyloid Polypeptide: What Is Its Relationship to Diabetes?

  1991cited by this paper
• Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose.

  1991cited by this paper
• Chronic intrarenal hyperinsulinemia does not cause hypertension.

  1991cited by this paper
• Abnormalities of Carbohydrate and Lipid Metabolism in Dahl Rats

  1991cited by this paper
• Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus.

  1991cited by this paper
• Interrelated effects of insulin and glucose on diacylglycerol-protein kinase-C signalling in rat adipocytes and solei muscle in vitro and in vivo in diabetic rats.

  1991cited by this paper
• Abnormalities of insulin and lipid metabolism in Milan hypertensive rats.

  1991cited by this paper
• Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension.

  1991cited by this paper
• Differential Effects of Diabetes on Adipocyte and Liver Phosphotyrosine and Phosphoserine Phosphatase Activities

  1991cited by this paper
• Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein

  1991cited by this paper
• Relationship between blood pressure, plasma insulin and triglyceride concentration, and insulin action in spontaneous hypertensive and Wistar-Kyoto rats.

  1991cited by this paper
• Insulin Resistance and Blood Pressure Regulation in Obese and Nonobese Subjects Special Lecture

  1991cited by this paper
• Sustained hyperinsulinemia increases arterial pressure in conscious rats.

  1991cited by this paper
• Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent.

  1991cited by this paper
• Insulin action kinetics in adipocytes from obese and noninsulin-dependent diabetes mellitus subjects: identification of multiple cellular defects in glucose transport.

  1991cited by this paper
• Insulin, insulin sensitivity and hypertension.

  1990cited by this paper
• A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance.

  1990cited by this paper
• Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus.

  1990cited by this paper
• Metabolic considerations in hypertension.

  1990cited by this paper
• Insulin-Receptor Autophosphorylation and Endogenous Substrate Phosphorylation in Human Adipocytes From Control, Obese, and NIDDM Subjects

  1990cited by this paper
• Lack of association between blood pressure and insulin in patients with insulinoma.

  1990cited by this paper
• Insulin signalling: search for the missing links.

  1990cited by this paper
• Effect of insulin on renal sodium handling in hypertensive rats.

  1990cited by this paper
• Insulin resistance and beta-cell hypersecretion in essential hypertension.

  1990cited by this paper
• Insulinemia and blood pressure. Relationships in patients with primary and secondary hypertension, and with or without glucose metabolism impairment.

  1990cited by this paper
• Hepatic protein phosphotyrosine phosphatase. Dephosphorylation of insulin and epidermal growth factor receptors in normal and alloxan diabetic rats.

  1990cited by this paper
• Effects of Insulin on Diacylglycerol–Protein Kinase C Signaling in Rat Diaphragm and Soleus Muscles and Relationship to Glucose Transport

  1990cited by this paper
• Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance.

  1990cited by this paper
• Chronic hyperinsulinemia and blood pressure regulation.

  1990cited by this paper
• Regulation of Glucose-Transporter Gene Expression In Vitro and In Vivo

  1990cited by this paper
• The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing.

  1990cited by this paper
• Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA study.

  1990cited by this paper
• Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene.

  1990cited by this paper
• Search for the missing links

  1990cited by this paper
• Structure and Function of Insulin Receptors

  1989cited by this paper
• Epidermal growth factor receptor defects in leprechaunism. A multiple growth factor-resistant syndrome.

  1989cited by this paper
• Insulin and Renal Sodium Retention in Obese Adolescents

  1989cited by this paper
• Banting lecture 1989. Structure and function of insulin receptors.

  1989cited by this paper
• A mutation in the insulin receptor gene that impairs transport of the receptor to the plasma membrane and causes insulin‐resistant diabetes.

  1989cited by this paper
• The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents.

  1989cited by this paper
• Antihypertensive effect of insulin reduction in diabetic-hypertensive patients.

  1989cited by this paper
• Hepatic phosphotyrosine phosphatase activity and its alterations in diabetic rats.

  1989cited by this paper
• Insulin resistance of uremia.

  1989cited by this paper
• A leucine‐to‐proline mutation in the insulin receptor in a family with insulin resistance.

  1989cited by this paper
• Abnormal insulin metabolism by specific organs from rats with spontaneous hypertension.

  1989cited by this paper
• Resistance to Insulin-Stimulated Glucose Uptake in Adipocytes Isolated From Spontaneously Hypertensive Rats

  1989cited by this paper

• Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

  2022cites this paper
• Effect of Olea europaea leaves extract on streptozotocin induced diabetes in male albino rats

  2017cites this paper
• 3-Deoxyglucosone induces insulin resistance by impairing insulin signaling in HepG2 cells.

  2016cites this paper
• A Prospective Study of Biochemical Assay in Mice Fed Refined Sugar Diet and Unrefined Sugar Diet

  2015cites this paper
• International Journal for Pharmaceutical Research Scholars (IJPRS)

  2014cites this paper
• Hypertension among HIV-Infected Adults Receiving Highly Active Antiretroviral Therapy (HAART) in Malaysia

  2013cites this paper
• Role of methylglyoxal in the pathogenesis of insulin resistance

  2010cites this paper
• Amelioration of Inducible Nitric Oxide Synthase, Insulin like Growth Factor-1 Gene Expression and Insulin Receptor Substrate-1 in Liver Tissue of Insulin Resistant Rats Treated With L-Carnitine

  2010cites this paper
• Accumulation of endogenous methylglyoxal impaired insulin signaling in adipose tissue of fructose-fed rats

  2007cites this paper
• Insulin Resistance and Hyperinsulinemia Are Related to Plasma Aldosterone Levels in Hypertensive Patients

  2007cites this paper
• Insulin Resistance and Hyperinsulinemia Are Related to Plasma Aldosterone Levels in Hypertensive Patients

  2007cites this paper
• L-CARNITINE ADMINISTRATION PREVENTS OXIDATIVE STRESS IN HIGH FRUCTOSE-FED INSULIN RESISTANT RATS

  2005cites this paper
• Potential role of kinins in the effects of taurine in high-fructose-fed rats.

  2004cites this paper
• Insulin receptors and renal sodium handling in hypertensive fructose-fed rats.

  2003cites this paper
• Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension.

  2003cites this paper
• Impact of gender on insulin signaling pathway in lacrimal and salivary glands of rats

  2002cites this paper
• Mechanisms underlying attenuated contractile response of aortic rings to noradrenaline in fructose-fed mice.

  2001cites this paper
• Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women: A dissociation contributing to low blood pressure?

  2000cites this paper
• Epidemiology of Risk Factors for Hypertension

  1999cites this paper
• Insulin resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats.

  1999cites this paper
• Epidemiology of risk factors for hypertension: implications for prevention and therapy.

  1999cites this paper
• Pregnancy‐induced hypertension and insulin resistance, evidence for a connection

  1999cites this paper
• Hypotensive effect of low-fat, high-carbohydrate diet can be independent of changes in plasma insulin concentrations.

  1999cites this paper
• DG 3 ‐ Deoxyglucosone induces insulin resistance by impairing insulin signaling in HepG 2 cells

  year unknowncites this paper