Insulin Resistance in Women with Polycystic Ovary Syndrome: Optimising treatment by Implementing an in vitro Insulin Resistance Organ Culture Model

Hardip Sandhu, Refik Kuburas

Research output: Contribution to journalArticle

Abstract

Polycystic ovary syndrome (PCOS) affects about 5-10% of fertile women and is characterised by insulin resistance (IR), dyslipidaemia, hyperandrogenism, and oligomenorrhoe. The metabolic disruption in PCOS women requires treatment to prevent the progression of IR to diabetes and cardiovascular disease. Metformin is currently first line treatment for metabolic/glycemic abnormalities, but lacks beneficial effect on IR PCOS patients with side-effects and cost outweighing
benefits. Rosiglitazone has shown to reduce IR,but it was recently withdrawn from the market due to severe side-effects. Basic research into developing optimised drug treatments for IR in PCOS is critical to reducing the development of PCOS associated diabetes and cardiovascular disease. Testing and optimising drugs to reduce IR in PCOS patient samples is difficult due to ethical restrictions. In vitro organ culture models are valuable and reliable. Coronary arteries incubated with high doses of insulin and glucose will be screened for reliable intracellular IR associated biomarkers by western blot and real time PCR analysis. Vascular function by wire-myograph analysis will validate endothelial dysfunction and assess myocardial vascular injury associated responses. The associated response to clinically relevant anti-diabetic treatment options and adjunct therapy will be investigated. Developing a PCOS IR simulated organ culture model will enable us to understand the complicated intracellular signalling mechanisms leading to IR and may lead to development of potential new drug therapy options improving the PCOS IR treatment outcome.
LanguageEnglish
Article number1000e107
Number of pages3
JournalClinics in Mother and Child Health
Volume12
Issue number2
DOIs
Publication statusPublished - 22 Jun 2015

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Polycystic Ovary Syndrome
Organ Culture Techniques
Insulin Resistance
Therapeutics
rosiglitazone
Cardiovascular Diseases
In Vitro Techniques
Hyperandrogenism
Metformin
Vascular System Injuries
Dyslipidemias
Pharmaceutical Preparations
Blood Vessels
Real-Time Polymerase Chain Reaction
Coronary Vessels
Biomarkers
Western Blotting
Insulin
Costs and Cost Analysis
Glucose

Bibliographical note

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

  • Polycystic ovary syndrome
  • Insulin resistance
  • Cardiovascular diseasesInsulin resistance organ culture model
  • Insulin resistance organ culture model
  • Insulin resistance therapy optimisation

Cite this

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title = "Insulin Resistance in Women with Polycystic Ovary Syndrome: Optimising treatment by Implementing an in vitro Insulin Resistance Organ Culture Model",
abstract = "Polycystic ovary syndrome (PCOS) affects about 5-10{\%} of fertile women and is characterised by insulin resistance (IR), dyslipidaemia, hyperandrogenism, and oligomenorrhoe. The metabolic disruption in PCOS women requires treatment to prevent the progression of IR to diabetes and cardiovascular disease. Metformin is currently first line treatment for metabolic/glycemic abnormalities, but lacks beneficial effect on IR PCOS patients with side-effects and cost outweighingbenefits. Rosiglitazone has shown to reduce IR,but it was recently withdrawn from the market due to severe side-effects. Basic research into developing optimised drug treatments for IR in PCOS is critical to reducing the development of PCOS associated diabetes and cardiovascular disease. Testing and optimising drugs to reduce IR in PCOS patient samples is difficult due to ethical restrictions. In vitro organ culture models are valuable and reliable. Coronary arteries incubated with high doses of insulin and glucose will be screened for reliable intracellular IR associated biomarkers by western blot and real time PCR analysis. Vascular function by wire-myograph analysis will validate endothelial dysfunction and assess myocardial vascular injury associated responses. The associated response to clinically relevant anti-diabetic treatment options and adjunct therapy will be investigated. Developing a PCOS IR simulated organ culture model will enable us to understand the complicated intracellular signalling mechanisms leading to IR and may lead to development of potential new drug therapy options improving the PCOS IR treatment outcome.",
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