The Endocrine Pancreas Flashcards
Define body energy
Energy intake minus energy output
What hypothalamic centres control energy intake?
Feeding centre- promotes feeling of hunger
Satiety centre- promotes feeling of fullness
Describe the glucostatic theory of energy balance
Food intake is determined by blood glucose- as [BG] increases, the drive to eat decreases
Describe the lipostatic theory of energy balance
Food intake is determined by fat stores: as fat stores increase, the drive to eat decreases. Leptin is a peptide hormone secreted by fat stores that depresses feeding activity
What are the three categories of energy output?
Cellular work Mechanical work Heat loss (associated with cellular and mechanical work- accounts for half of energy output)
When in the feeding cycle is the body in an anabolic and a catabolic state?
After eating we enter an anabolic state to store food
Between meals and overnight we enter a catabolic state to break down food to use body stores
Through what processes is blood glucose maintained?
Synthesising glucose from glycogen (glycogenesis) or amino acids (gluconeogenesis)
What is the given normal range for blood glucose, and what value is considered to be hypoglycaemic?
Normal= 4.2-6.3mM Hypoglycaemia= <3mM
Where are the hormones for the endocrine pancreas produced?
In the islets of Langerhans
What are the four types of islet cells and what does each produce?
Alpha cells- glucagon
Beta cells- insulin
Delta cells- somatostatin
F cells- pancreatic polypeptide
What two substances control the balance of blood glucose, and in which state is each more prominent?
Insulin and glucagon
Insulin dominates in fed state
Glucagon dominates in fasted state
What are the stimuli for insulin secretion?
Blood glucose concentration (most major stimulus)
Glucagon
[Amino acids] plasma
Vargas nerve activity
How is excess glucose stored?
As glycogen in the liver and muscle
As triacylglycerols in the liver and adipose tissue
Describe the mechanism of control of insulin secretion by [BG]
B cells have a specific type of potassium ion channel that is sensitive to [ATP] within the cell known as the K ATP channel
When glucose is abundant it enters cells through GLUT and metabolism increases, increasing [ATP] within the cell, causing the K ATP channel to close. This leads to a build up of Intracellular [K+], depolarising the cell. Voltage-dependent Ca2+ channels then open and trigger insulin vesicle exocytosis into the circulation.
Describe the primary action of insulin
Insulin binds to tyrosine kinase receptors on the cell membrane of insulin-sensitive tissues and stimulates the mobilisation of GLUT-4, which usually resides in the cytoplasm of unstimulated cells. When stimulated, it migrates to the membrane and is able to transport glucose into the cell. When insulin stimulation stops, the GLUT-4 transporters return to the cytoplasm.
What types of tissue are sensitive to insulin?
Muscle and fat
How does the liver take up insulin?
Through GLUT 2 transporters
What are the main additional actions of insulin?
Increases glycogen synthesis in muscle and liver. Stimulates glycogen synthase and inhibits glycogen phosphorylase
Increases amino acid uptake into muscle, promoting protein synthesis
Increases protein synthesis and inhibits proteolysis
Increases triacylglycerol synthesis in adipocytes and liver
Inhibits the enzymes of gluconeogenesis in the liver
Has a permissive effect on growth hormone
Promotes potassium ion entry into cells by stimulating sodium/potassium ATPase
What are the stimuli than inhibit insulin release?
Low [BG]
Somatostatin
Sympathetic a2 effects
Stress eg hypoxia
What is the function of glucagon and where is its main site of action?
Primary function is to raise blood glucose
Main site of action is liver
Describe the main characteristics of glucagon receptors
They are G-protein coupled receptors linked to adenylate cyclase/cAMP system which phosphorylates specific liver enzymes when activated
What are the results of activation of glucagon receptors?
Increased glycogenolysis
Increased gluconeogenesis
Formations of ketones from fatty acids
What are the effects of amino acids on secretion of insulin and glucagon?
Amino acids in plasma stimulate the release of both insulin and glucagon
What stimuli promote glucagon release?
Low [BG] High [amino acids] Sympathetic innervation and epinephrine Cortisol Stress eg exercise
What stimuli inhibit glucagon release?
Glucose
Free fatty acids and ketones
Insulin
Somatostatin
Describe the parasympathetic innervation of islet cells
Increased parasympathetic activity through the vagus nerve leads to increased insulin secretion and to a lesser extent, increased glucagon secretion. This is in association with the anticipatory phase of digestion
Describe the sympathetic activity of islet cells
Increased sympathetic activity promotes glucose metabolisation, leading to increased glucagon and increased epinephrine and inhibition of insulin.
What is the main pancreatic function of somatostatin?
To inhibit activity in the GI tract to slow down absorption and prevent exaggerated leaks in plasma concentrations of nutrients
How does exercise alter glucose uptake?
In active muscle, GLUT4 transported can migrate to the membrane without insulin being present, so exercise causes uptake of glucose independent of insulin
What is the energy source for the brain in periods of prolonged starvation?
Ketones
How is energy sourced during periods of starvation?
When nutrients are scarce, the body relies on stores for energy and breaks down adipose tissue into fatty acids. Free fatty acids can be used readily by most tissues to produce energy, and the liver will convert the excess to ketone bodies to provide energy for the brain
Describe the effect of poorly controlled insulin-dependent diabetes on ketone absorption
A lack of insulin deceases the rate of uptake of ketones, meaning that they accumulate in the plasma and cause life threatening acidosis due to their acidic nature
