Ganong 24e chapter 24 - Endocrine Pancreas (1)

Question 1

What proportion of the volume of the pancreas is made of β-islet cells? And of exocrine cells?

Answer 1

2% β-islet cells, 80% exocrine cells.

Question 2

What is the venous drainage of the pancreas?

Answer 2

Blood from the pancreas drains into the hepatic portal vein.

Question 3

Name three of the four polypeptides with regulatory activity that are secreted by the islets of Langerhans, and which cells they come from.

Answer 3

A cells: Glucagon
B cells: Insulin
D cells: Somatostatin
F cells: Pancreatic Polypeptide

Question 4

Describe the structure of insulin in basic terms.

Answer 4

Insulin is a polypeptide of two chains of amino acids linked by two disulphide bridges.

Question 5

What are the precursor molecules to insulin? Where are they made?

Answer 5

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.

Question 6

What is C peptide?

Answer 6

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.

Question 7

What is the half-life of insulin in the bloodstream?

Answer 7

5 minutes

Question 8

What happens to insulin once it has bound to insulin receptors?

Answer 8

It is endocytosed and then destroyed by proteases in the endosomes.

Question 9

Give an overview of the effects of insulin.

Answer 9

Insulin is anabolic. It causes glucose uptake into cells, synthesis of lipids and proteins and glycogen, potassium uptake, and reduction in gluconeogenesis.

Question 10

What does insulin do in the adipose tissue?

Answer 10

It increases glucose uptake, potassium uptake, and fatty acid synthesis

Question 11

What does insulin do in the muscle?

Answer 11

It increases glucose uptake, potassium uptake, protein synthesis and glycogen synthesis

Question 12

What does insulin do in the liver?

Answer 12

It decreases ketogenesis, decreases gluconeogenesis, and increases synthesis of glycogen, proteins and lipids.

Question 13

How does insulin increase intracellular potassium?

Answer 13

It increases the activity of Na+/K+/ATP-ase, which pumps potassium into the cell.

Question 14

How does glucose enter cells (in the majority of circumstances)? How does glucose enter cells in the intestinal wall and kidneys?

Answer 14

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).

Question 15

Which glucose transporter is found in muscle and adipose tissue and is stimulated by insulin?

Answer 15

GLUT-4

Question 16

What are the most rapid actions of insulin? How long does it take for this to happen?

Answer 16

Increased uptake of glucose, amino acids and potassium occurs within seconds.

Question 17

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?

Answer 17

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.

Question 18

How does insulin cause glucose uptake in the liver cells?

Answer 18

It induces glucokinase, which increases the phosphorylation of glucose, facilitating the entry of glucose into the cell.

Question 19

What type of receptor is the insulin receptor?

Answer 19

A trans-membrane tyrosine-kinase receptor.

Question 20

What is the half-life of the insulin receptor? How does it get broken down?

Answer 20

About 7 hours. After insulin binds to the receptor, the insulin-receptor complex gets endocytosed and broken down by lysosomes.

Question 21

What is HbA1c?

Answer 21

This is formed when haemoglobin A is glycated. This occurs when plasma glucose is episodically elevated over time.

Question 22

In a patient developing DKA, how do the ketone bodies arise?

Answer 22

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.

Question 23

How can a diabetic become acidotic?

Answer 23

Excess ketone bodies (which are acids)

Question 24

Why is potassium lost in the urine of diabetics?

Answer 24

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.

Question 25

Name four hormones that are released in response to falling plasma glucose levels below 4mmol/L

Answer 25

Glucagon, Epinephrine, Cortisol, Growth Hormone

Question 26

What happens when glucose comes in contact with pancreatic B-cells?

Answer 26

Glucose enters the cell via GLUT-2 transporters. Basically, it triggers the exocytosis of insulin granules, and it does this by mechanisms involving ATP production from the citric acid cycle, reduced K+ efflux and increased Ca2+ influx.

Question 27

Name as many stimulators of insulin secretion as you can.

Answer 27

Glucose, Mannose, Amino acids, Intestinal hormones (gastrin, secretin, CCK), Ketones, ACh (vagal stimulation), Glucagon, cAMP, Theophylline, Sulfonylureas, β-adrenergic stimulators

Question 28

Name as many inhibitors of insulin secretion as you can.

Answer 28

Somatostatin, 2-Deoxyglucose, Mannoheptulose, Galanin, Diazoxide, Thiazide diuretics, Potassium depletion, Phenytoin, Alloxan, Microtubule inhibitors, Insulin, β-adrenergic blockers (propranolol), α-adrenergic stimulators (adrenaline, noradrenaline)

Question 29

For each of the following substances, explain whether glucagon causes its production or its breakdown:
Glycogen, Glucose, Lipids, Ketones.

Answer 29

Glucagon causes Glycogenolysis, Gluconeogenesis, Lipolysis, Ketogenesis.

Question 30

For each of the following substances, explain whether insulin causes its production or its breakdown:
Glycogen, Glucose, Lipids, Ketones.

Answer 30

Insulin causes Glycogen production, reduced gluconeogenesis, reduced lipolysis and reduced ketogenesis.

Question 31

In which tissues does glucagon cause glycogenolysis?

Answer 31

In the liver. NOT in the muscle.

Question 32

What is the half-life of glucagon in the circulation?

Answer 32

5-10 minutes.

Question 33

Name some of the stimulators of glucagon secretion.

Answer 33

Amino acids (protein meal), CCK, gastrin, Cortisol, Exercise, Infections, Starvation, Other stresses, β-adrenergic stimulators (sympathetics), Theophylline, ACh (vagal stimulation)

Question 34

Name some of the inhibitors of glucagon secretion.

Answer 34

Glucose, Somatostatin, Secretin, FFA, Ketones, Insulin, Phenytoin, α-adrenergic stimulators, GABA

Question 35

Name five factors that are stimulators of both insulin secretion and glucagon secretion.

Answer 35

Protein meal (amino acids)
Theophylline
Vagal stimulation (acetylcholine)
CCK, gastrin
Beta-agonists

Question 36

Name four factors that are inhibitors of both insulin secretion and glucagon secretion

Answer 36

Somatostatin
Insulin
Phenytoin
α-adrenergic stimulators

Question 37

How does glucagon cause glycogenolysis in the liver cells?

Answer 37

Glucagon binds to a G-protein linked receptor –> this activates adenylyl cyclase in the hepatic cell membrane, which promotes glycogenolysis.