effects of type ii diabetes on coronary vasodilation
DESCRIPTION
Effects of Type II diabetes on coronary vasodilation. By Matthew Cozier Research Project 3003MSC Supervisor: Roselyn Rose'Meyer Lab partners; Lynette Burges & Katie Crane. Overview. Aims & Hypothesis Introduction Epidemiology of diabetes, Effects of hyperglycemia - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/1.jpg)
Effects of Type II diabetes on coronary vasodilation.
• By Matthew Cozier
Research Project 3003MSC
• Supervisor: Roselyn Rose'Meyer• Lab partners; Lynette Burges & Katie Crane
![Page 2: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/2.jpg)
Overview
1. Aims & Hypothesis
2. Introduction– Epidemiology of diabetes, – Effects of hyperglycemia – Coronary heart disease & pathological mechanisms
3. Materials & Methods
4. Results
5. Discussion & Conclusion
![Page 3: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/3.jpg)
Hypothesis
Type II diabetes affects the mechanism of ischemia induced vasodilation, and potentiates the risk of coronary heart disease.
(Cozier et al., 2008)(Cozier et al., 2008)
![Page 4: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/4.jpg)
AimsTo measure
Coronary vasodilatory mechanisms
Fasting blood glucose levels,
Blood pressure,
Heart and body weight,
Coronary flow rate
Potassium levels in adipose and skeletal muscle tissues.
Between groups consisting of male Wistar rats with or without 3
weeks dietary intervention of 5% glucose, and age-matched Zucker
obsese rats
![Page 5: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/5.jpg)
Introduction
• Diabetes Melitus (DM) is a 'metabolic syndrome'.• DM associated with the onset & progression of
coronary heart disease (CHD)†
• Accounts for 10% of the global expenditure of health care.*
† Hanley AJ, Williams K, Stern MP, Haffner SM (2002): Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care 25: 1177–1184, 2002.* Diabetes Atlas. Gan D, Ed. Brussels, Belgium, International Diabetes Federation, 2003
![Page 6: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/6.jpg)
Worldwide mortality of diabetes
Wild SH., Roglic G., Green a., Sicree R., King H., Global Prevalence of Diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care 27;(5)1047-1053
(Wild et al., 2000)(Wild et al., 2000)
<3%<3%
<3%<3%
3-5%3-5%
3-5%3-5%
3-5%3-5%
6-8%6-8%
6-8%6-8%>8%>8%
Suboptimal Suboptimal provision of health provision of health care for diabeticscare for diabetics
High prevalence of High prevalence of type II diabetes high type II diabetes high –associated with –associated with increased obesityincreased obesity
![Page 7: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/7.jpg)
Diabetes Epidemiology & Projections
• Worldwide by 2010; 218.3 Million people 97% will have Type II Diabetes.
2 out of 3 patients with type II diabetes will suffer from cardiovascular disease... 141.9 Million people
Diabetes is the greatest risk factor for CHD*
* de Courten M, Zimmet P (1997) Screening for non-insulin-dependent diabetes mellitus: where to draw the line. Diabet Med 14: 95±98 Danaei G., Lawes C.M., Vander Hoorn S., et al., Global and regional mortality from ischaemic heart disease and stroke attribute to higher-than-optimum blood glucose concentration: Comparative risk assessment. Lancet. 2006; 368:1651-1659.
![Page 8: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/8.jpg)
Type II Diabetes
• Resistance to insulin and hyperglycemia.• Attributed to obesity, poor diet and lack of
exercise.• Progresses from a state of ’pre-diabetes.’
– Pre-diabetes; Similar symptoms exist – yet glucose levels considered sub-acute
• Signs & Symptoms; – increased thirst, – increased hunger,– fatigue, – increased urination, especially at night, – weight loss, blurred vision, – sores that do not heal.
![Page 9: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/9.jpg)
The pathobiology of diabetes Type II
• Affects physiology– Hyperglycemia– Dehydration– Hypokalemia– Ketoacidosis
![Page 10: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/10.jpg)
The pathobiology of diabetes Type II
• Affects cell biology– Cell metabolism → produciton of O
2 radicals
– Cell signalling - intracellular signalling cascades.– Cell function (tissue specific)
• -->> Vasodilatory mechanisms << --
Cardiovascular complications.
![Page 11: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/11.jpg)
Mechanisms of ischemia induced Vasodilation
• 2 main Pathways– NO induced
• Nitric oxide is derived from many tissues end product of arginine catabolism, catalysed by NOS.
Mechanism of Action. NO → NO receptor → cGMP → PKG → Relaxation of Smooth muscle.
Nitroprusside - NO receptor Agonists;
![Page 12: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/12.jpg)
Mechanisms of ischemia induced Vasodilation
• Adenosine Mediated• Adenosine is the end product of ATP
dephosphorylation
Adenosine → A2 Adenosine Receptors
→ cAMP → PKA → K-ATP channel activation → Hyperpolarisation of the cell membrane → vasodilation.
A link between metabolic state of the heart and function of the cardiac vasculature.
NECA; Adenosine AnalogueDiazoxide; K-ATP channel opener
![Page 13: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/13.jpg)
The Downward Spiral.
Myocardial Myocardial InfarctionInfarction
Myocardial Myocardial IschemiaIschemia
Poor Poor PerfusionPerfusion
Tissue Tissue Necrosis & Necrosis & Tissue Tissue DamageDamage
Cardiac Cardiac DysfunctionDysfunction
DeathDeath
BadBad
Much
Much Badness
Badness
ReperfusionReperfusion
Tissue Tissue RecoveryRecovery
Normal Normal Function of Function of the heartthe heart
Green = VasodilationGreen = Vasodilation
Red = No VasodilationRed = No Vasodilation
![Page 14: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/14.jpg)
Materials & Methods
• Animal Models;– 12 Male Wistar Rats
• 6 Control• 6 rats Glucose treated - fed upon a diet consisting of 5%
– 6 Male Zucker obese Rats
![Page 15: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/15.jpg)
The Zucker Rat
![Page 16: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/16.jpg)
Materials & Methods
Langendorf reperfusion apparatus...
• Heart Rates• Coronary pressure• LVDP• Rate of ventricular systole• Rate of ventricular diastole
![Page 17: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/17.jpg)
![Page 18: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/18.jpg)
Results
* P < 0.05 vs Control† P < 0.05 vs Glucose treated
![Page 19: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/19.jpg)
Results
* P < 0.05 vs Control† P < 0.05 vs Glucose treated
![Page 20: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/20.jpg)
Results
![Page 21: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/21.jpg)
* P < 0.05 vs Control† P < 0.05 vs Glucose treated
Results
![Page 22: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/22.jpg)
* P < 0.05 vs Control
Results
**
![Page 23: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/23.jpg)
* P < 0.05 vs Control
Results
![Page 24: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/24.jpg)
* P < 0.05 vs Control
Results
![Page 25: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/25.jpg)
* P < 0.05 vs Control
Results
![Page 26: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/26.jpg)
* P < 0.05 vs Control
Results
[Nitroprusside][Nitroprusside]
![Page 27: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/27.jpg)
Conclusions• Both glucose treated and Zucker obese rats are
pre-diabetic. – Insulin resistance observed– Hyperglycemia– Exhibited some degree of resistance to the diazoxide,
NECA and nitroprusside.
• Type II diabetes attenuates the coronary vasodilatory response to myocardial ischemia. – May explain the reduced recovery rates in those
suffering from both diabetes and cardiovascular heart disease.
All aims have been achieved; experiment successful.
![Page 28: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/28.jpg)
Future Directions
• Determine how diabetes affects the actions of endogenous and exogenous vasodilatory compounds
• Determine the diabetic rat hearts sensitivity to numerous vasoconstrictors, and new drugs that have not yet been considered such as glibenclamide.
• Identify how the body handles potassium in type II diabetes and determine how this may impact upon vasodilation.
• Use the Zucker lean rats may as a more suitable candidate for further experimentation in order to reduce genetic variability between populations and yield more precise data.
• Take advantage of novel methods of observing the ‘energetics’ of the heart in order to observe the effects of diabetes at a metabolic level.
• Investigate protein modification and levels of expression in myocytes, vascular endothelium and many other cell types isolated from rats with II diabetes.
![Page 29: Effects of Type II diabetes on coronary vasodilation](https://reader036.vdocuments.us/reader036/viewer/2022062315/56814bc8550346895db89f85/html5/thumbnails/29.jpg)
Roselyn Rose’MeyerRoselyn Rose’Meyer
Lynette Burges & Katie Crane