7 - Sweet nothings Flashcards
What are the 6 glucose transporters and their tissue locations?
GLUT 1 - red cells, brain placenta GLUT 2 - Liver, kidney, pancreatic b cell, intestine GLUT 3 - Brain GLUT 4 - Muscle, Fat GLUT 5 - jejunum SGLT1 - dudenum, jejunum, kidney
What drives glucose symport across the SGLT1 transporter?
Na+
What are the 2 glucose transporters in the intestine and kidney, where are the located on the membrane?
SGLT1 on the intestinal lumen side (in between microvillus)
GLUT2 on the basal domain (extracellular side)
What are some of the metabolic consequences of untreated diabetes? (there are 11)
Catabolism promoted, increase in glucagon secetion, glycogen mobilised, gluconeogenesis increased, tissue protein degredation increased, glucose utilisation diminished, adipose issue lipolysis increased, clearance of plasma triglyceride diminished, fatty acid utilisation increased, ketone body production increased, plasma PH falls.
What are the complications of intracellular hyperglycaemia from diabetes in terms of the microvasculature (arterioles and capillaries)
Blood flow abnormalities, increase vascular permeability (elaboration of VEGF), decreased vasodialation (reduced VO), increased vasoconstriction, disrupted extracellular matrix, deposition of modified plasma proteins.
How does does hyperglycaemia affect the
a) retina
b) kidney
c) nerves
Retina = oedema, ischaemia, neovascularisation Kidney = proteinuria, mesangial matrix expansion, glomerulosclerosis Nerves = peripheral mulifocal axon degeneration
What are the complications of endothelial dysfunction in diabetes?
Intracellular hyperglycaemia Decreased NO and smooth muscle cell prliferation
What is the complication of dyslipidaemia (abnormal amount of lipids in blood)?
Elevation of apo B (proteins of LDL’s) containing remnants
How does hyperglcaemia cause changes in polyol metabolism?
Glucose -> sorbitol utilizing NADPH (enzyme aldose reductase)
sorbitol -> Fructose
(using SDH)
How much glucose does diabetic polyol synthesis consume
a) % in lens
b) % in red cells
33% of total glucose in the lens
11% of total glucose in red cells
What are the 4 main ways that hyperglycaemia causes damage?
1) Changes in polyol metabolism
2) Advanced glycation end-products
3) Activation of protein kinase C
4) Increased hexosamine pathway activity
How does a hyperglycaemic endothelial cell interact with a marcophage/mesangial cell and what is the final product?
Advanced glycation end products produces AGE plasma proteins.
These interact with the AGE receptor on the macrophage, activating reactive oxygen species.
These interact with transcription factors to increase production of growth factors and cytokines.
Protein kinase C:
A family of at least eleven isoforms, __ of which
are activated by diacylglycerol
Intracellular diacylglycerol is synthesised from the glycolytic intermediate _______
A family of at least eleven isoforms, nine of which
are activated by diacylglycerol
Intracellular diacylglycerol is synthesised from the glycolytic intermediate dihydroxyaxcetone phosphate
What are some events that are activated by increased levels of protein kinase C?
Blood flow abnormalities Vascular permeability angiogenesis Capillary occlusion Vascular occlusion Pro-inflammatory gene expression Increased reactive oxygen species formation leading to growth factor production
When the mitochondrial proton electrochemical
gradient is large, _______ accumulate and
superoxide is produced.
Mitochondrial depolarisation or overexpression of
_____________________ prevent
hyperglycaemia-induced overproduction of
reactive oxygen species
When the mitochondrial proton electrochemical
gradient is large, semiquinones accumulate and
superoxide is produced.
Mitochondrial depolarisation or overexpression of
manganese superoxide dismutase prevent
hyperglycaemia-induced overproduction of reactive oxygen species
