The endocrine Pancreas Flashcards
What does SGLTs mean?
Sodium-Glucose cotransporters
Secondary Active transport
SGLT 1
Glucose Absorption from the gut
SGLT1, SGULT2
Glucose reabsorption from the kidney (PCT)
GLUT 1
Brain, erythrocytes - a high affinity for glucose: constant uptake of glucose at 2-6 mM
GLUT2
Liver, kidney, pancreas, gut- low-affinity- glucose equilibrates across the membrane
-Glucose-dependent insulin release in the pancreas
GLUT3
Brain - high affinity
GLUT4
Muscle and adipose - a medium affinity. Insulin recruits transporters
-Insulin-dependent uptake of glucose into cells
Islets of Langerhans
Clusters of endocrine cells surrounded by exocrine pancreas
alpha- cells
Glucagon
Beta cells
Insulin
Delta cells
Somatostatin
How is insulin made?
Pre-pro insulin - signal sequence removed - proinsulin (in the rough endoplasmic reticulum)
Transfer to Golgi apparatus- peptidases break off the C peptide leaving an A and B chain linked by disulfide bonds
One mole of C-peptide is secreted for each molecule of insulin
What arteries supply the pancreas?
Ceoliac, superior mesenteric, and splenic arteries
Where does venous drainage of the pancreas go to?
The portal vein
Where is half of the insulin metabolised?
By the liver
How do beta cells detect a rise in glucose?
There are no glucose receptors so GLUT2/glucokinase can be thought of as the sensor.
Effector is rise in ATP due to glucose oxidation
What family is the insulin receptor in?
Tyrosine kinase superfamily
What happens when insulin binds to the insulin receptor?
- Activates a cascade of protein phosphorylation, which stimulate or inhibit specific metabolic enzymes by modulating enzyme phosphorylation.
- Modulates the activity of metabolic enzymes by regulating gene transcription
Type 1 classification diabetes mellitus
Absolute insulin deficiency (due to destruction of insulin-producing pancreatic beta cells)
Type 2 classification diabetes mellitus
Variable combination of insulin resistance and insulin insufficiency
What fasting concentration of plasma glucose indicates diabetes?
> /= 7.0 mmolL-1
What % is good for glycaemic control?
6.5%
Treatment for type 2 diabetes
Metformin: decreases gluconeogenesis
Sulfonylureas: Bind and close KATP channels, depolarize B cells releasing insulin
Thiazolidinediones: activate PPARgama receptor (controller of lipid metabolism), which reduces insulin resistance
SGLT2 inhibitors: promote glucose excretion via kidney
Incretin targeting drugs: potentiate insulin release in response to rising plasma glucose
What does DPP-4 inhibitors
Prevent breakdown of natural incretins
