Ganong 24e chapter 24 - Endocrine Pancreas (1) Flashcards
What proportion of the volume of the pancreas is made of β-islet cells? And of exocrine cells?
2% β-islet cells, 80% exocrine cells.
What is the venous drainage of the pancreas?
Blood from the pancreas drains into the hepatic portal vein.
Name three of the four polypeptides with regulatory activity that are secreted by the islets of Langerhans, and which cells they come from.
A cells: Glucagon
B cells: Insulin
D cells: Somatostatin
F cells: Pancreatic Polypeptide
Describe the structure of insulin in basic terms.
Insulin is a polypeptide of two chains of amino acids linked by two disulphide bridges.
What are the precursor molecules to insulin? Where are they made?
Preproinsulin is made in the RER. It has a section cleaved off, then it becomes folded and disulphide bonds are added, and then it is called proinsulin.
What is C peptide?
C-peptide (connecting peptide) is used to fold preproinsulin. It connects the A-chain and the B-chain (the amino acid chains). The serum levels of C-peptide are used as an index of B-islet-cell function in patients receiving exogenous insulin.
What is the half-life of insulin in the bloodstream?
5 minutes
What happens to insulin once it has bound to insulin receptors?
It is endocytosed and then destroyed by proteases in the endosomes.
Give an overview of the effects of insulin.
Insulin is anabolic. It causes glucose uptake into cells, synthesis of lipids and proteins and glycogen, potassium uptake, and reduction in gluconeogenesis.
What does insulin do in the adipose tissue?
It increases glucose uptake, potassium uptake, and fatty acid synthesis
What does insulin do in the muscle?
It increases glucose uptake, potassium uptake, protein synthesis and glycogen synthesis
What does insulin do in the liver?
It decreases ketogenesis, decreases gluconeogenesis, and increases synthesis of glycogen, proteins and lipids.
How does insulin increase intracellular potassium?
It increases the activity of Na+/K+/ATP-ase, which pumps potassium into the cell.
How does glucose enter cells (in the majority of circumstances)? How does glucose enter cells in the intestinal wall and kidneys?
In the majority of cases: by facilitated diffusion. This means that it moves down its concentration gradient through a carrier protein, without the need for ATP.
In the intestinal wall and kidneys: by secondary active transport. This means that a Na/K/ATPase pumps Na+ out of the basolateral membrane, causing a flow of Na+ from the lumen into the cell down its concentration gradient, and glucose accompanies it through the cotransporter (SGLT-1 or SGLT-2).
Which glucose transporter is found in muscle and adipose tissue and is stimulated by insulin?
GLUT-4
What are the most rapid actions of insulin? How long does it take for this to happen?
Increased uptake of glucose, amino acids and potassium occurs within seconds.
How does insulin increase the number of GLUT-4 transporters on a muscle cell’s membrane? How does the decline in insulin cause a reduced number of GLUT transporters?
Insulin binds to insulin receptors. This stimulates pools of vesicles within the cell to come and fuse with the cell membrane. The vesicles have GLUT transporters in them. When insulin action ceases, the GLUT transporters are endocytosed, and remain in the cytoplasm as vesicles.
How does insulin cause glucose uptake in the liver cells?
It induces glucokinase, which increases the phosphorylation of glucose, facilitating the entry of glucose into the cell.
What type of receptor is the insulin receptor?
A trans-membrane tyrosine-kinase receptor.
What is the half-life of the insulin receptor? How does it get broken down?
About 7 hours. After insulin binds to the receptor, the insulin-receptor complex gets endocytosed and broken down by lysosomes.
What is HbA1c?
This is formed when haemoglobin A is glycated. This occurs when plasma glucose is episodically elevated over time.
In a patient developing DKA, how do the ketone bodies arise?
There is increased lipolysis, and so fatty acids accumulate in the bloodstream, and they are catabolized in the liver to acetyl-CoA. The supply of acetyl-CoA exceeds the capacity of the tissues to use it in the citric acid cycle, and so the excess acetyl-CoA is converted to ketone bodies.
How can a diabetic become acidotic?
Excess ketone bodies (which are acids)
Why is potassium lost in the urine of diabetics?
The organic anions (ketone bodies) require accompanying cations in order to be excreted in the urine. The kidneys provide H+ and NH4+ as part of the buffering system. However, when this is exhausted, the plasma Na+ and K+ become the cations accompanying the organic anions in urinary excretion.
