Diabetic Kidney Disease Flashcards
What two scientists found out insulin prevents diabetes?
Best and Banting
what are 2 cell types in the islet of langerhans?
Beta cells
alpha cells
What do beta cells secret?
Insulin
What do alpha cells secrete?
Glucagon
Why is the best way to adminster glucose and why?
Oral is the best way to adminster glucose to get insulin response -> specific gut hormones that induce insulin
What are 2 gut hormones that induce the insulin response?
GLP-1 and GIP -> gut hormones (incretin response)
What happens when beta cells take up glucose?
ATP generation & closure of K+ channel -> membrane depolarization -> calcium entry -> insulin rich granules released
What is the insulin receptor made up of?
Polypeptide composed of alpha and beta chains
What type of receptors are insulin receptors?
Tyrosine receptor kinases
What glucose transporter translocate to membrane when tyrosine kinase activity increase?
GLUT - 4
What are 3 treatments for T1DM?
Insulin replacement
Pancreas transplant
beta cell therapy
What is treatment for T2DM?
Diet and exercise
Oral hypoglycemic agents
What are examples of oral hypoglycemic agents?
Stimulate beta cell insulin secretion
Decrease hepatic production of glucose
Increase glucose sensitivity
incretin mimetics
SGLT2 inhibitors
What are complication associated with diabetes?
Retinopathy
Nephropathy
Neuropathy -> amputations
Stroke
CVD
What is the leading cause of end stage renal disease?
Diabetic kidney disease
What is the earliest sign of diabetic kidney disease?
Microalbuminuria
How do you block RAS?
ACE inhibitors
ANG receptor blockade
What does persistent albuminuria tell us?
Kidneys are not filtering properly
What happens when GFR goes down?
Increase risk of ESRD
What are structural changes in DKD?
Glomerular enlargement
Celullar hypertrophy (TGF-B)
Tubular interstitial fibrosis
Increased ROS
TIF reflects?
growth factors
proteinuria
ischemia
hypoxia
Which kidney arterioles are constricted in diabetes?
Efferent arterioles
What can reduce pressure in efferent arterioles?
ACE inhibitors
Why is progress in this field slow?
Mice are not humans - difficult to mimic DKD in mice
Not good biomarkers
What is the MoA of SGLT2 inhibtors
stop reabsorption of glucose in kidneys which decreased reabsorption of sodium as well -> resloves glomerular hypertension
What is MCP?
Chemokine that is attracted to monocytes
How is inflammation targeted?
Anti-inflammatory drugs
JAK-STAT
