The Endocrine Pancreas Flashcards
Body energy = X - Y
Energy intake - energy output
What two hypothalmic centres control energy intake?
Feeding centre - Promotes feeling of hunger and drive to eat
Satiety centre - Promotes feelings of fullness by suppressing feeding centres
What is the glucostatic theory ?
As Blood Glucose increases the drive to eat decreases
What is the lipostatic theory ?
As fat stores increase the drive to eat decreases
What is leptin?
A peptide hormone which is released from fat cells and suppresses feeding activity
What are the 3 categories of energy output?
Cellular work
Mechanical work
Heat loss
What does cellular work involve?
Transporting molecules across membranes
Growth and repair
Storage of energy via fat, glycogen, ATP
What is mechanical work?
Movement via muscle or intracellular movement
What accounts for half of energy output?
Heat loss
What to anabolic pathways do?
Build up smaller molecules into larger ones for storage
What do catabolic pathways do?
Break down large molecules into smaller ones to release energy
What happens after we eat?
We enter into an absorptive state which is anabolic
If energy input exceeds bodies need excess is stored
What happens between meals and overnight?
A post absorptive/fasting state
Bodies stores give energy - catabolic state
What does 99% of the pancreas operate as?
An exocrine gland that releases enzymes and Sodium Bicarbonate into the GI tract to support digestion
What does the 1% do?
Functions as endocrine
Where is the pancreas’ hormones made?
In islets of langerhans - tiny clusters of cells
4 types of islet cells and their products?
Alpha - glucagon
Beta - insulin
Delta - Somatostatin
F - pancreatic polypeptide
What is the function of pancreatic polypeptide?
Not really known
What organ is a obligatory glucose utiliser and what does this mean?
The brain
Means it can only use glucose for energy
The brain can use fats, carbs and proteins for energy when glucose is low - T or F
False - can only use ketones
How does the brain get glucose in the fasting state?
BG conc. is maintained by making glucose from glycogenolysis or gluconeogenesis
What is glycogenolysis and gluconeogenesis
GGL - glycogen to glucose
GNG - amino acids and non-carbs
What is normal BG conc?
4.2-6.3 mM
or
80-120 mg/dl
When is a patient hypoglycemic?
BG is lower than 3mM
What type of hormone is insulin?
A peptide hormone
How is insulin made?
Synthesised as a large preporhormone - then cleaved into proinsulin by ER
Proinsulin stored as granules in secretory vesicles
Inside the granule proinsulin is cleaved to form insulin and the fragment c-peptide
It is stored in this form til the B-cell is activated and it will be secreted
What does insulin do?
Stimulates glucose uptake by cells decreasing BG conc.
Do any other hormones decrease blood glucose?
No only insulin
What stimulates insulin secretion?
Glucose (BG most important) and amino acids
What happens to excess glucose?
Stored as glycogen in liver and muscle and as triacylglyceride in liver and adipose tissue
What are amino acids converted to in excess?
Fat
What are fatty acids stored as and where?
TAG in adipose tissue and liver
What causes insulin to be secreted from cells when BG conc. is high?
When glucose is abundant in blood it enters cells via GLUT transporters and metabolism increases
This increases ATP in the cell
This closes the K-ATP channel causing K+ to rise in the cell depolarising it
This leads to voltage dependant Ca2+ channels to open triggering insulin vesicle exocytosis into cirulation
What happens to stop insulin secretion when BG conc. is low?
Low BG conc = low ATP in cell
Causes K-ATP channels to open letting K+ leave the cell causing hyperpolarisation
This closes the Ca2+ channels and stops insulin secretion
What is the primary action of insulin?
Binds to tyrosine kinase receptors of the cell membrane of insulin-sensitive tissues
This stimulates GLUT-4 which resides in muscle and adipose tissue cytoplasms
This leads to increases in glucose uptake for muscles and adipose tissue
What tissues are insulin sensitive and what transporter do they use?
Muscle and fat
GLUT-4
What does GLUT-1 and GLUT-3 do?
Non insulin-dependent glucose uptake in many tissues such as brain, kidney, RBCs
What does GLUT-2 do?
Glucose uptake in B-cells of pancreas and liver
Does insulin have any direct effect on the livers glucose uptake?
No - is independent of insulin using GLUT-2 and a gradient
How does insulin indirectly effect the livers glucose uptake?
Glucose transported into hepatocytes is still affected by insulin status
In the fed state insulin binds to liver cells which causes intracellular glucose to convert into glucose-6-phosphate to maintain the gradient
What happens to liver cells in the fasted state?
In the fasted state - liver makes glucose via glycogenolysis and gluconeogenesis creating a glucose gradient that moves glucose out into the blood
What are some additional actions of insulin?
Increases glycogen synthesis
Increases amino acid uptake/protein synthesis
Increases TAG and lipocyte synthesis
Has permissive effect on GH
Inhibits gluconeogensis in liver
Promotes K+ ion entry into cells by stimulating the K/Na-ATPase
What increases insulin release?
Increase in BG conc. Increase in AA conc. Glucagon (in ketosis) Other incretin hormones Vagal activity
Why does glucagon stimulate insulin when it has the opposite affects?
Insulin needed for uptake of glucose made from gluconeogenesis
What are incretin hormones?
Hormones that stimulate a decrease in BG conc.
Where are incretin hormones released? In response to what and why?
Jejunem and ileum in response to nutrients
Released so that an early insulin response prevents a BG surge once the nutrients are absorbed
Name some incretin hormones?
Secretin CCK GLP-1 GIP Gastrin
Does vagal activity release insulin when glucose is taken orally or via IV?
Orally so insulin response via IV will be less than orally
Why does oral glucose increase insulin response more than IV glucose?
In IV only b-cells release insulin
In oral - insulin increased via b-cells, vagal activity and incretin horomes
What stimuli inhibit insulin release?
Low BG conc
Somatostatin
Sympathetic alpha 2 effects
Stress - hypoxia
What type of hormone is glucagon? Where is it made and what does it do?
Peptide
Alpha cells
Raise BG conc.
Where does glucagon mainly act?
Liver
What is glucagon’s plasma half-life? What is it degraded by?
5-10 mins
By liver
What is the glucose counter-regulatory control system and what hormones does it involve? When is the system most active?
System that opposes action of insulin
Glycogen
Adrenaline
Cortisol
GH
Fasting state
What type of receptors are glucagon receptors? What happens once they activate?
GPCRs linked to the adenylate-cyclase/cAMP system
Receptor phosphorylates specific liver enzymes
What does the phosphorylation of these liver enzymes cause?
Increases glycogenolysis and gluconeogenesis
Forms ketones from fatty acids (lipolysis)
This causes increased BG conc.
Is glucagon secretion constant? When does it spike?
Yes it is quite constant but spikes when BG conc. is less than 5.6 mM
What is a more significant measurement of glucagon than just looking at its blood conc?
It’s ratio to insulin
How do AAs effect glucagon secretion?
Stimulates it
Why do AAs stimulate glucagon and insulin?
To adjust for a meal very high in proteins with no carbs to stop insulin lowering BG levels to dangerous levels without the carbs to replace it
List things that promote glucagon release.
Low BG AAs Sympathetic innervation and adrenaline on B2 receptors Cortisol Stress - exercise or infection
List things that inhibit glucagon release.
High blood glucose
Free fatty acids and ketones
Insulin
Somatostatin
What inbitory mechanism for glucagon fails in diabetes resulting in very high BG conc?
Insulin no longer inhibits glucagon secretion so it will secrete rising BG
Describe the ANS innervation of islet cells.
Parasympathetic activity via vagus nerve leads to:
Increased insulin and small increase in glucagon in anticipation of digestion
Sympathetic innervation - increase in glucagon and adrenaline, inhibition of insulin
In summary glucagon causes…
Liver glycogenolysis
Gluconeogenesis
Adrenaline causes…
Muscle and Liver glycogenolysis
Gluconeogenesis
Lipolysis
Cortisol causes…
Gluconeogenesis
Inhibition of glucose uptake
Lipolysis
Protein catabolism
GH causes…
Gluconeogenesis
Inhibition of glucose uptake
Lipolysis
What type of hormone is somatostatin?
A peptide hormone
What cells secrete somatostatin?
D cells of the pancreas
Hypothalmic cells
What is another name for somatostatin?
GH inhibiting hormone - inhibits GH release from AP gland
Pancreatic function of somatostatin?
Inhibit activity in the GI tract
Slows down absorption of nutrients to prevent exaggerated peaks in plasma conc.
What can synthetic somatostatin be used for?
Help patients with life threatening diarrhoea associated with gut or pancreatic tumours
Is somatostatin a counter-regulatory hormone in controlling glucose?
No but it does strongly supress release on insulin and glucagon in a paracrine chemical fashion (locally)
What do patients with pancreatic somatostatin secreting tumours present with?
Symptoms of diabetes that go away after tumour is removed
How does exercise disrupt the steady state? How long do these effects last?
During exercise glucose entry into skeletal muscle is increased even in absence of insulin
Exercise also increases insulin sensitivity of muscle
Effects last for several hours
How does exercise increase muscle sensitivity to insulin?
GLUT-4 transporters can migrate to the membrane without insulin being present causing increased sensitivity to insulin
How does starvation disrupt the steady state ?
Adipose tissue –> FFAs –> Ketones
FFAs can be used readily by most tissues
What does the starvation response spare?
Muscle tissue from being broken down by gluconeogenesis
Why is muscle breakdown bad?
Leaves body prone to infections and weak
