Lecture 31 - Coordinating Metabolism: Insulin and Glucose Transport Flashcards
What is metabolic homeostasis
The body’s ability to maintain various metabolic processes to ensure molecules essential for life are kept at an optimal level
What is the preferred fuel type for the brain?
Glucose but can use ketone bodies as well
What is the preferred fuel type for resting skeletal muscle?
Fatty acids
What does resting skeletal muscle store?
Glycogen
What is the preferred fuel type for exercising skeletal muscle?
All; glucose, fatty acids, branch-chain amino acids
What fuels are exported from exercising skeletal muscle?
Lactate and alanine
What is the preferred fuel type for cardiac muscle?
Fatty acids
What is the preferred fuel type for the adipose tissue?
Fatty acids
What fuel is stored in adipose tissue?
Triacylglycerols
What fuel is exported from adipose tissue?
Fatty acids and glycerol
What is the preferred fuel type for the liver?
Amino acids, glucose and fatty acids
What fuel is stored in the liver?
Glycogen
What fuels are exported from the liver?
Triacylglycerols, glucose, ketone bodies
What is the prefered fuel for RBCs?
Glucose
What fuel is exported from RBCs?
Lactate
Why can the brain not use FAs?
They cannot cross the blood-brain barrier
What can the RBCs not use FAs?
They lack mitochondria
What is insulin?
A peptide hormone synthesised in the pancreas by the beta cells
When is insulin secreted?
In response to high glucose levels
What does insulin do?
Acts on the liver, muscle and adipose tissues to promote glucose transport and use
What happens to the body without insulin?
It starves
What is type 1 diabetes?
An early onset form of diabetes, diagnosed by symptoms, blood glucose and glycated haemoglobin
What are common symptoms of diabetes?
Glycosuria (glucose in urine) and the presence of ketones in the blood
What causes type 1 diabetes?
An autoimmune condition leading to the loss of pancreatic beta cells and therefore no insulin secretion
What is preproinsulin?
Initial form of insulin synthesised from transcription and translation - in the ER
What does preproinsulin contain?
An A-chain, B-chain, C-peptide, and a signal sequence
What is the signal sequence?
A chain that helps direct the protein into the ER but is removed by signal peptidase, leaving proinsulin
What is proinsulin?
The A-chain, B-chain, and C-peptide of insulin. It moves to the Golgi and is packaged into secretory granules. Proprotein convertase enzymes in the granules cleave proinsulin to release active insulin (A-chain and B-chain) and C-peptide.
What is the C-peptide?
A chain released during the cleavage of proinsulin along with insulin, has a longer half-life than insulin and can be used as a marker of insulin secretion
What is the c-peptide important for?
Distinguishing between endogenous insulin and exogenous insulin
How does glucose stimulate insulin secretion?
GLUT1 transports glucose into pancreatic beta cells, glucose is metabolised via glycolysis and the CAC to increase ATP levels. Increased ATP:ADP ratio inhibits ATP-gated K+ channels triggering membrane depolarisation and the opening of voltage-gated Ca2+ channels. The calcium influx induces exocytosis of insulin-containing secretory vesicles
When are glucose levels the highest?
About an hour after eating
When are insulin levels the highest?
About two hours after eating
What is the incretin effect?
The phenomenon where oral glucose intake stimulates a greater insulin response compared to an equivalent amount of glucose administered intravenously
Why does oral insulin work better?
Due to the action of gut-derived hormones; GLP-1
Why does insulin have to be taken intravenously?
Gets broken down in GI tract
What is GLP-1 in the L-cells of the intestine an example of?
A different way of processing the same protein (similar to insulin)
What is GLP-1?
A peptide hormone synthesised in the intestine in response to nutrients
What is GLP-1 made from?
Glucagon via convertase enzyme
What does GLP-1 do?
Acts through its receptor to stimulate insulin secretion
How is GLP-1 used to treat type 2 diabetes?
Agonists are developed
How does GLP-1 promote weight loss?
Slows gastric emptying and reduces appetite
What is GLUT4?
An insulin-regulated glucose transporter
Where is GLUT4 found in muscle and adipose cells?
Intracellular storage vesicles
What happen when insulin binds to its receptor?
A phosphorylation cascade is activated that regulates the trafficking of GLUT4 vesicles to the plasma membrane by regulating vesicle trafficking proteins
What is GSV?
The GLUT4 storage vesicle
What does AS160 do?
Regulates a GTPase protein Rab10 which is involved in the trafficking of vesicles
What is IRS?
Insulin receptor substrate
What is PIP2 and PIP3?
Membrane phospholipids
What is the insulin receptor an example of?
A tyrosine kinase receptor
