Hormones of the Endocrine Pancreas Flashcards
Describe how glucose travels in the body.
- Glucose in blood taken up by muscle and liver cells as glucose-6-phosphate (G-6-P).
- If not needed, stored via Glycogenesis as Glycogen.
- When needed converted back to G-6-P via glycogenolysis (using the hormone glucagon produced by alpha cells of the pancreas).
- Used by both muscle and liver to produce ATP via glycolysis and oxidative phosphorylation.
- In liver, converted by an enzyme back into glucose in the blood.
- Liver also synthesizes new glucose via glyconeogenesis. Uses amino acids, glycerol and lactate.
Describe the process of lipolysis.
- Conversion of triglycerides (via the enzyme lipase) into fatty acids and glycerol. Occurs in adipose tissue.
- Glycerol released into blood, taken up by liver and used in glyconeogenesis or triglyceride (TG) synthesis.
- Fatty acids taken up by cells and used in ATP production (convert to acetyl CoA).
- Fatty acids taken up by liver and used in many functions.
What is Ketogenesis.
The production of ketones in the liver.
1. Fatty acids enter the liver. A derivative of fatty acids is acetyl CoA.
2. Acetyl CoA is converted to ketones.
3. The liver lacks the enzymes to convert ketones back to acetyl CoA so they are released into the blood.
4. Ketones taken up by muscle and brain cells and converted to acetyl CoA and used in ATP production.
Describe the pancreatic islet cells.
These are the endocrine cells of the pancreas that produce and secrete hormones.
- Alpha cells = glucagon
- Beta cells = insulin and amylin (most predominant)
- Delta cells = gastrin and somatastatin.
- F Cells = pancreatic polypeptides.
NOTE: Ancinar cells are exocrine cells of the pancreas that synthesize, store and secrete digestive enzymes.
What is Insulin (describe the production).
A water-soluble protein hormone.
1. Preproinsulin produced in the ER.
2. Cleaved in the golgi apparatus to proinsulin (inactive).
3. Cleaved into (active) insulin and c-peptide (a by-product of insulin).
4. Both released in same amount when B cells stimulated.
5. C-peptide more easily detectable in blood and 24 hour urine sample = can be used as an indirect measure of insulin and b cell function.
Insulin secretion
Basal release q15min even when fasting.
4 ways to stimulate:
1. Blood glucose >4mM
2. Digestive enzymes GIP, GLP-1 (glucagon-like peptide)
3. Elevated levels of some amino acids
4. parasympathetic stimulation via the vagus nerve (ACh) - occurs when food enters the digestive system and stretches the digestive tract.
NOTE: sympathetic stimulation (Epi, NE) will inhibit beta cell activiation.
Describe the response to high blood glucose when eating.
- Blood glucose (>4mM) enters b cells and stimulates release of insulin.
- Stretch receptors in the digestive tract respond to eating food and stimulate the release of ACh by the parasympathetic systems which stimulates b cell release of insulin.
- Circulating insulin promotes the uptake and utilisation of insulin.
- Decreased blood glucose levels have a negative feedback and halt b cell stimulation.
Describe how glucose stimulates a beta cell.
- Glucose enters the beta cell via the GLUT-2 transporter.
- Glukokinase phosphorylates glucose to G-6-P.
- G-6-P metabolized to ATP via glycolysis.
- ATP closes ATP-sensitive K+ channels.
- Intracellular K+ rises causing cell depolarization.
- Cell depolarization causes opening of voltage-gated Ca2+ channels to open.
- Ca2+ enters and mobilizes granules to release insulin from the cell via exocytosis.
What are the phases of insulin release with eating.
Biphasic patter with feeding in response to increased BG.
1. 1st phase = stored insulin releases causing a peak in 3-5 mins.
2. 2nd phase = gradual increase then return to normal over 2-3 hours as new insulin is produced.
Describe how Ozempic works.
- GLP-1 (glucagon-like peptide) is released by cells of the intestinal tract in response to consuming glucose.
- GLP-1 stimulates beta cells to release insulin and prohibits alpha cells from releasing glucagon (which play a role in glycogenolysis and the subsequent increase in BG).
- GLP-1 agonists (semaglutide) are used in the management of DMII
- Other effects of GLP-1 are the slowing of GI motility and decreasing appetite (being used for weight loss).
How is insulin transported.
Since it is a water-soluble protein hormone, not a lipid-soluble hormone, it does not require a carrier to travel through the blood.
Has a short circulating half-life of 3-5 mins.
50% of initial removal of insulin occurs in the liver (pancreas to the hepatic portal vein).
Other target cells are muscle and adipose tissue.
What are insulin receptors?
Plasma membrane insulin receptors are found on most cells in the body.
When they bind insulin it triggers signalling pathways that produce cellular effects.
What are the 3 effects of insulin on the cell.
- nutrient uptake (glucose into liver, skeletal and adipose cells, amino acids into skeletal cells, fatty acids into adipose cells)
- metabolic effects = nutrient storage as glycogen, proteins or TG and prevention of the breakdown of already stored nutrients.
- protein synthesis
Describe glucose uptake in muscle and adipose cells.
Insulin stimulates (plasma membrane receptors that bind and trigger signalling pathways) movement of GLUT-4 transporters from vesicles in cell to plasma membrane.
GLUT-4 transportation increases glucose transport 10-21 fold.
Describe glucose uptake in the liver.
Glucose diffuses across via GLUT-2 transporters.
Insulin triggers the enzyme glucokinase to convert glucose to G-6-P.
As long as BG is elevated, glucose will continue to diffuse across GLUT-2.
NOTE: liver cells do not contain GLUT-4
NOTE: glucose beyond glycogen stores is converted to TG for storage in liver.
