Endocrine Physiology - The Endocrine Pancreas Flashcards
What is a normal fasting blood glucose level?
Less than 5.6mmol/L
Normal range of [BG] and hypoglycaemic [BG]
Normal range 4.2-6.3 mmol/L
Hypoglycaemia <3 mmol/L
Which hormone dominates the absorptive state?
Insulin
How is excess glucose stored?
Excess glucose is stored as glycogen in liver and muscle and as triacylglycerols (TAG) in liver and adipose tissue.
Mechanism of action of insulin.
- Insulin binds to tyrosine kinase receptors on the cell membrane of insulin sensitive tissues to increase glucose uptake by these tissues.
- In muscle and adipose tissue, insulin stimulates the mobilisation of specific glucose transporters, GLUT-4, which reside in the cytoplasm of these cells.
- When stimulated by insulin GLUT-4 migrates to the membane and is them able to transport glucose into the cell.
Additional actions of insulin.
- Increases glycogen synthesis in muscle and liver - stimulates glycogen synthase and inhibits glycogen phosphorylase
- Increases amino acid uptake into muscles
- Increases protein synthesis and inhibits proteolysis
- Increases triacylglycerol synthesis in adipocytes and liver
All of the above are anabolic processes or inhibit catabolism.
- Promotes K+ ion entry into cells by stimulating Na+/K+ ATPase
Stimuli which increase insulin release:
- Increases [BG]
- Increased [amino acid] plasma
- Glucagon
- Other hormones controlling GI secretion and motility released in response to nutrients
- Vagal nerve activity
Stimuli which inhibit insulin release.
- Low [BG]
- Somatostatin (GHIH)
- Sympathetic alpha-2 effects
- Stress eg hypoxia
Why does glucagon stimulate insulin release?
Glucagon stimulates gluconeogenesis which creates glucose that requires insulin to be taken up.
How does the liver take up glucose?
The liver takes up glucose by GLUT-2 transporters, which are insulin independent. Glucose enters down a concentration gradient.
Why is the insulin response to an intravenous glucose load less than the equivalent amount of glucose administered orally?
- IV glucose → ↑ insulin by direct effect of ↑ glucose on B-cells
- oral loading of same amount of glucose → ↑ insulin by both direct effect on B-cells and vagal stimulation of B-cells, plus incretin effects
Which type of cells produce glucagon?
Alpha-cells of the pancreatic islet cells
What is the action of glucagon and when is it most active?
Opposes the action of glucose. It is most active in the post absorptive state.
Which hormones form the glucose counter regulatory control system?
- Glucagon
- Epinephine
- Cortisol
- Growth hormone
Effect of glucagon:
- Increased glycogenolysis
- Increases gluconeogenesis
- Formation of ketones from fatty acids (lipolysis)
All these processes occur in the liver.
Net result is elevated [BG]
Stimuli that promote glucagon release:
- low [BG] (<5mM)
- high [amino acid] - prevents hypoglycaemia following insulin release in response to aa
- sympathetic innervation and epinephrine, B2 effect
- cortisol
- stress eg exercise, infection
Stimuli that inhibit glucagon release
- Glucose
- Free fatty acids (FFA) and ketones
- Insulin (fails in diabetes so glucagon levels rise despite high [BG])
- Somatostatin
ANS innervation of islet cells
- ↑ parasympathetic activity (vagus) → ↑ insulin and to a lesser extent ↑ glucagon, in associated with the anticipatory phase of digestion
- ↑ sympathetic activation promotes glucose mobilisation → ↑ glucagon, ↑ epinephrine and inhibition of insulin (all appropriate for fight or flight response)
Why does amino acid in the plasma stimulate the release of both insulin and glucagon?
AAs → ↑ insulin → ↓ [BG]
AAs → ↑ glucagon → ↑ [BG]
The effect of insulin on [BG] is counteracted by glucagons glucose mobilising effects and so [BG] is maintained.
How does the release of insulin impact on the release of glucagon and vice versa?
Insulin suppresses the release of glucagon and
glucagon has an insulin secreting effect.
How does exercise change glucose metabolism?
- The entry of glucose into skeletal muscle is increased during exercise, even in the absence of insulin.
- Exercise also increases the insulin sensitivity of muscle, and causes an insulin-independent ↑ in the number of GLUT-4 transporters incorporated into the muscle membrane.
- The effect persists for several hours after exercise and regular exercise can produce prolonged increases in insulin sensitivity.
How does starvation change metabolism?
When nutrients are scarce, the body relies on stores for energy - adipose tissue is broken down releasing fatty acids. FFAs can be readily used by most tissues to produce energy and the liver will convert excess to ketone bodies which provides an additional source for muscle and brain.
How does diabetes affect metabolism?
Diabetes is similar to starvation in that there is a lack of access to nutrients.
However, in poorly controlled insulin dependent diabetes a lack of insulin depresses ketone body uptake. They build up rapidly in the plasma and create life threatening acidosis.
