? Diabetic Nephropathy
? Diabetic Cardiomyopathy
? Diabetic Retinopathy
? Diabetic Neuropathy
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Four distinct mechanisms
1-Formation of Advanced Glycation End Products. Advanced glycation
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end products (AGEs) are formed as intracellular
glucose derived dicarbonyl precursors+ amino groups
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advanced glycation end product(AGEs)(glyoxal, methylglyoxal, and 3-deoxyglucosone)
? AGEs bind to a specific receptor (RAGE) that is expressed on
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inflammatory cells (macrophages and T cells), endothelium, and
vascular smooth muscle.
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AGE-RAGE signal ing axis? TGF-excess basement membrane material
? vascular endothelial growth factor (VEGF)- neovasculerization
? reactive oxygen species (ROS) in endothelial cells
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? procoagulant activity? Enhanced proliferation of vascular smooth muscle cells and synthesis
of extracellular matrix
2-Activation of Protein Kinase C.
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second messenger diacyl glycerol (DAG) is an important signaltransduction pathway.
Intracellular hyperglycemia--- de novo synthesis of DAG--excessive
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PKC activation- vascular permeability and angiogenesis3-Oxidative Stress and Disturbances in Polyol Pathways
? Sustained hyperglycemia---- aldol reductase-- progressive depletion of
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intracellular NADPH -- decreased rgeneration of reduced
glutathione(GSH) - increasing cellular susceptibility to oxidative
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stress4-Hexosamine Pathways and Generation of Fructose-6- Phosphate
Hyperglycemia ---increases intracellular levels of fructose-6-
phosphate via HM- excess proteoglycans - abnormal
expression of TGF or PAI-1--- exacerbate the end-organ damage
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Pancreas
Pancreatic Islets-
1-Insulitis:
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? In type 1 DM-?lymphocytic infiltrate,macrophage and few polymorphs
? In type 2 DM-
?variable degree of fibrous tissue in the islets
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2-Islet cell mass:
? Type-1- loss of pancreatic -cells and its hyalinisation
? In type 2 DM-hyperplasia and hypertrophy of islets
3-Amyloidosis:
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? type 1 DM- absent? Type-2DM-around the capillaries of the islets causing compression
and atrophy of islet tissue
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Diabetic Nephropathy
Nephrosclerosis
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Pathogenesis in Diabetic nephropathy
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Diabetic Retinopathy
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Intra retinal microangiopathy (IRMA)(NPDR)
Neovascularization
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Diabetic Cardiomyopathy
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Diabetic Neuropathy--- Content provided by FirstRanker.com ---