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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)
08:13

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)

Published on: January 7, 2018

Insulin resistance and cardiovascular risk: New insights from molecular and cellular biology

Carmine Morisco1, Giuseppe Lembo, Bruno Trimarco

  • 1Dipartimento di Medicina Clinica Scienze Cardiovascolari ed Immunologiche, Université FEDERICO II Napoli, 80131 Napoli, Italy. cmorisco@yahoo.com

Trends in Cardiovascular Medicine
|July 15, 2006
PubMed

Insights

Insulin resistance, linked to cardiovascular diseases, involves disrupted insulin signaling pathways. Understanding these molecular mechanisms is key to developing treatments that reduce cardiovascular risk.

Area of Science:

  • Biochemistry
  • Cardiovascular Medicine
  • Endocrinology

Background:

  • Insulin resistance is a hallmark of conditions like diabetes, obesity, and hypertension, significantly increasing cardiovascular risk.
  • Abnormalities in insulin signaling, particularly the phosphorylation of the insulin receptor (IR) and IR substrates (IRS), underlie insulin resistance.
  • Dysregulation of the sympathetic nervous and renin-angiotensin systems contributes to both cardiovascular diseases and insulin resistance.

Purpose of the Study:

  • To elucidate the molecular mechanisms driving insulin resistance.
  • To identify potential therapeutic targets for endothelial and metabolic dysfunction.
  • To reduce cardiovascular risk and improve patient outcomes in insulin resistance states.

Main Methods:

  • Investigated mechanisms inhibiting insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate (IRS) proteins.
  • Examined the roles of proteasome-mediated degradation, phosphatase activity, and kinase-mediated serine/threonine phosphorylation.
  • Analyzed the impact of specific phosphorylation sites (Ser612, Ser307) on IRS-1 signaling and stability.

Main Results:

  • Identified key inhibitory mechanisms in insulin resistance, including IRS-1 phosphorylation at Ser612 and Ser307.
  • Ser612 phosphorylation disrupts phosphatidylinositol 3-kinase signaling, while Ser307 phosphorylation leads to IR dissociation and proteasomal degradation.
  • Highlighted the interplay between cardiovascular disease pathways (sympathetic nervous, renin-angiotensin systems) and insulin resistance pathogenesis.

Conclusions:

  • Characterizing molecular pathways of insulin resistance is crucial for therapeutic development.
  • Targeting these mechanisms may ameliorate metabolic dysfunction and reduce cardiovascular risk.
  • Further research can lead to novel pharmacologic strategies for managing insulin resistance-associated conditions.

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