Endocrinology Flashcards
Regarding metabolism in the fed state, where are glucose and AAs transported
From intestine to the blood
Regarding metabolism in the fed state, where are dietary lipids transported
From the lymphatic system to the blood
What does insulin stimulate
Storage of fuels and synthesis of proteins
What is the fuel reserve of a well-fed human
161,000 kcal
Energy needed for a 24 hr period
1600-6000 kcal
- sufficient reserves for starvation up to 1-3 months
- however glucose reserves are exhausted < 1 day
Even under starvation what must the blood-glucose level be above
40 mg/100 ml
In prolonged starvation, what is the first priority
Sufficient glucose for brain, nervous tissue, RBC
In prolonged starvation, what is the 2nd priority
Preserve protein - lipolysis & gluconeogenesis
After 3 days of starvation what do the brain and heart start to do
Use ketones as fuel
After several weeks of starvation, what is the major fuel of the brain
Ketone bodies
What happens when TAG stores must be used (prolonged starvation)
Increase protein degraded
Decrease heart, liver and kidney function
What happens to 1. Glucose 2. Ketone body and 3. FA conc in plasma during starvation
- Decreases but remains above 3-4 mM
- Increases rapidly
3, Increases slowly
Decreasing order of total body metabolic fuel
- Fat
- Protein
- Muscle glycogen
- Hepatic glycogen
- Circulating nutrients
Decreasing order of circulating fuel
- glucose
2. TAGs & free FAs
What is the exocrine pancreas associated with
Acini - digestion (99%)
What is the endocrine pancreas associated with
Islets of Langerhans - control of blood glucose (1%)
What do the beta cells of the islets of langerhans release
Insulin (see photo)
What do the alpha cells of the islets of langerhans release
glucagon (see photo)
What do the gamma cells of the islets of langerhans release
Somatostatin
Where are pancreatic polypeptides found and what do they do
Found between acinar cells and inhibit pancreatic secretion of fluid
What is optimal blood glucose concentration
Normal fasting level = 90-100mg/100 mls (5mM)
Effect of an increase in glucose on insulin
Increased insulin
Effect of a decrease in glucose on insulin
Decreased insulin
Vascularisation of islets
Richly vascularised
- 1-2% of pancreas but 10-15% pancreatic blood flow
Effect of increasing plasma AAs on insulin
Large increase in insulin
Effect of increasing free FAs on insulin
Increase in insulin
Effect of increasing Glucagon on insulin
Increase in insulin
Effect of increasing GH & GIT hormones on insulin
Increase in insulin
What are the islets modulated by
ANS innervation - modulate insulin and glucagon secretion
Which has a greater effect - orally administered glucose or IV administered glucose
Orally administered
- glucagon, glucagon derivatives, secretin, cholecystokinin & gastric inhibitory peptide stimulate insulin secretion
What is the incretin effect
Gut-derived factors that enhance glucose-stimulated insulin secretion from the islet beta-cell
ie a graph re-iterating that oral glucose has a greater effect than IV glucose infusion
Where is Glucagon-like polypeptide 1 (GLP-1) synthesised
Within L cells located predominantly in ileum and colon & a lesser number in the duodenum and jejunum
What does GLP-1 do
- stimulates insulin secretion
- suppresses glucagon secretion
- slows gastric emptying
- reduces food intake
- increases beta cell mass
- maintains beta cell function (decreases beta cell apoptosis)
- improves insulin sensitivity (muscle)
- enhances glucose disposal (decreases glucose production in liver)
- Increases cardiac protection and CO
- decreases appetite
- increases neuroprotection
What effect of GLP-1 is preserved in type 2 diabetes
Glucose lowering effects
- Tissue distribution & 2. Special properties of GLUT 1
- Most cells
- High capacity
Relatively low Km (5mM) => high substrate affinity
- Tissue distribution & 2. Special properties of GLUT 2
1. Liver beta cells hypothalamus basolateral membrane of SI 2. High capacity but low affinity => high Km (15-20mM) Part of the glucose sensor in beta-cells
- Tissue distribution & 2. Special properties of GLUT 3
- Neurons
Placenta
testes - Low Km (1mM) and high capacity
- Tissue distribution & 2. Special properties of GLUT 4
1. Skeletal muscle Cardiac muscle Fat 2. Activated by insulin Km = 5mM
- Tissue distribution & 2. Special properties of GLUT 5
- SI mucosal surface
sperm - Primarily fructose carrier in intestine