Pathobiology of diabetic complications
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This document summarizes the pathobiology of complications from diabetes mellitus. It introduces the three main types of diabetes and describes some of the major complications like retinopathy, cardiomyopathy, nephropathy, and neuropathy. It then discusses the pathogenesis of diabetes complications, outlining several key pathways involved like the polyol pathway, advanced glycation end product formation, protein kinase C activation, and the hexosamine pathway. References are provided to support the information presented.
Pathobiology of diabetic complications
- 1. Presented by Guide Mr. Gogawale Vinayak G. M.Pharm. (Semester-II) (Department of Pharmacology) Dr. U.M.Aswar (Pharmacology) SINHGAD INSTITUTE OF PHARMACY, NARHE PATHOBIOLOGY OF DIABETIC COMPLICATIONS 4/4/2015 1
- 2. CONTENTS • Introduction . • Complications in diabetes . • Pathogenesis of complications of diabetes. • References. 4/4/2015 2
- 3. • Diabetes mellitus is a group of chronic disorders characterize by the hyperglycemia. • Types of diabetes: 1. Type I diabetes mellitus 2. Type II diabetes mellitus 3. Gestational diabetes mellitus 4/4/2015 3 INTRODUCTION
- 4. • Type I diabetes mellitus: - It is characterized by the bodies disability to produce insulin due to autoimmune destruction of beta cells of pancreas. -It generally occur in the childhood and in adults at late 30s or early 40s. 4/4/2015 4
- 5. 4/4/2015 5 Mechanism of type I diabetes mellitus
- 6. • Type II diabetes mellitus: -It is caused due to lack of insulin secretion and insulin resistance action of body which cause hyperglycemia. - 4/4/2015 6
- 7. 4/4/2015 7 Mechanism of type II diabetes mellitus
- 8. Complications in diabetes mellitus 4/4/2015 8
- 9. • s complications 4/4/2015 9 Types of diabetes complications Eye: • Retinopathy Heart: • Cardiomyopathy Kidney: • Nephropathy Neuropathy
- 10. Retinopathy: • Diabetic retinopathy characterized by the growth of new blood vessels on the retina and posterior surface of the vitreous. • It causes the loss of vision of both eyes. 4/4/2015 10 Eye
- 11. Eye 4/4/2015 11
- 12. • Stages of retinopathy: 4/4/2015 12 Retinopathy Mild nonproliferative retinopathy Moderate nonproliferatve retinopathy Severe nonproliferative retinopathy Proliferative retinopathy
- 13. Cardiomyopathy • It is a disorder in which the myocardium get affects and shows left ventricular hypertrophy. • Diastolic and systolic dysfunction or in combination. • Patients who suffer from the coronary artery diseases as well as hypertension they shows synergic adverse effect. 4/4/2015 13 Heart
- 16. Nephropathy • Diabetic nephropathy is clinical syndrome characterized by decreasing glomerular filtration rate, glomerular hypertrophy, tubulointerstitial fibrosis, decreased excretion of albumin and decreased creatinine clearance. 4/4/2015 16 Kidney
- 17. • Stages of Nephropathy: 4/4/2015 17 Nephropathy Glomerular hypertrophy Mesangial expansion Micro albuminuria Overt-proteinuria Hypertension End stage renal disease
- 18. Neuropathy Neuropathy • It is the symptoms of dysfunction of the peripheral nerve which resembles in pain. • Changes in the blood vessels supplying the peripheral nerves underlie the mechanisms involved in micro vascular damage and hypoxia. 4/4/2015 18
- 20. Pathways causes complications of diabetes • Polyol pathway • Advanced glycation end product formation • Protein kinase C • Hexosamine pathway. 4/4/2015 20 Pathogenesis of complications of diabetes
- 21. Increased polyol pathway flux • Aldose reductase is the enzyme in the polyol pathway. • It is cytosolic, monomeric oxidoreductase that catalyses the NADPH dependent reduction of wide variety of carbonyl compounds including glucose. • The metabolism of the glucose from this pathway is in small percentage than the total glucose use. 4/4/2015 21
- 22. • The polyol pathway involves two enzymatic reactions the first is the reduction of glucose to sorbitol by the action of aldose reductase and the second oxidation of sorbitol to fructose by the action of sorbitol dehydrogenase. 4/4/2015 22 Increased polyol pathway flux
- 23. Increased polyol pathway flux 4/4/2015 23
- 24. Advanced glycation end product formation • It is a non enzymatic reaction in free amino acids and carbonyl compounds or carbonyl groups of reducing sugar called as Millard reaction. • It is three stage reaction as follows: 1. Early stage 2. Intermediate stage 3. Late stage 4/4/2015 24
- 25. Advanced glycation end product formation 4/4/2015 25
- 26. Protein Kinase C • Diacylglycerol is produced as well as inosytol triphosphate whenever receptor induced phosphotidyl inositol hydrolysis occurs. • The main effect of diacylglycerol is to activate memabrane bound protein kinase which catalyses the phosphorylation of intracellular proteins 4/4/2015 26
- 27. Protein Kinase C 4/4/2015 27
- 28. Hexosamine pathway • Fructose 6 phosphate is converted glucosamine 6 phosphate,catalysed by first and end relating enzyme glutamine fructose 6 phosphate amidotransferase (GFAT). The major end product is UDP N acetylglucosamine (UDP-GlcNAc) require to formation of O- linked glycoprotein 4/4/2015 28
- 30. References • Schalkwijk C. G., Stehouwer C. D., “Vascular Complications In Diabetes Mellitus: The Role Of Endothelial Dysfunction”, Clinical Science (2005) 109, 143–159. • Sharma V., Sharma P.L., “Role of Different Molecular Pathways in the Development of Diabetes-Induced Nephropathy” ISSN(2013) 2155-6156 JDM. • Zychowska M.,et al. “Mechanisms And Pharmacology Of Diabeticneuropathy – Experimental And Clinical Studies.”ISSN(2013)1601-1610. 4/4/2015 30
- 31. References • Singh V. P. et al., “Advanced Glycation End Products and Diabetic Complications” , Korean J Physiol Pharmacol(2014) vol 18,1-14. • Brownlee M., “Biochemistry and molecular cell biology of diabetic complications”, Nature (2001) vol 414, 813-820. 4/4/2015 31