The Endocrine Pancreas Flashcards
Where is energy intake determined by the activity in?
Feeding centre
Satiety centre
What does the feeding centre promote?
Feelings of hunger and makes us want to eat
What does the satiety centre promote?
Feelings of fullness and stop us eating
Describe the glucostatic theory?
Food intake is determined by BG
As BG increases the drive to eat decreases
Describe the lipostatic theory?
Food intake is determined by fat stores
As fat stores increase the drive to eat decreases
What is leptin?
A peptide hormone released by adipose tissue to decrease feeding activity
What are the 3 categories of energy output?
Cellular work
Mechanical work
Heat loss
What is mechanical output?
Movement on large scale
Only part we can control
By skeletal muscle
What is metabolism?
Integration of all biochemical reaction in the body
What are the 3 elements of metabolism?
Extracting energy from nutrients in food
Storing that energy
Utilising that energy for work
What are anabolic pathways?
Pathways that build up using energy
Synthesis of larger molecules from smaller ones
What are catabolic pathways?
Pathways that break down releasing energy
Degradation of large molecules into smaller ones releasing energy
What is the absorptive state?
Where ingested nutrients supply the energy needs of the body and the excess is stored
Is the absorptive state anabolic or catabolic?
Anabolic
What is the absorptive state dominated by?
Insulin
What is the fasted state?
Where we rely on body stores in our bodies to provide energy
Is the fasted state anabolic or catabolic?
Catabolic
What is the fasted stage dominated by?
Glucagon
What is glucose stored in the body in the form of?
Glycogen
What can the brain only use to provide energy?
Glucose
Why must we maintain BG in the fasted state?
To meet the brains requirements
Where is glycogen stored?
Liver
Where will glucose present in hyperglycaemia?
In the Urine
What occurs in the failure to maintain BG?
Hypoglycaemia
What is glycogenolysis?
The synthesis of glucose from glycogen
What is gluconeogenesis?
The synthesis of glucose from amino acids
What is the normal range of glucose conc.?
4.2-6.3 mM
What is considered hypoglycaemia?
<3mM
What are the 2 key endocrine hormones produced in the pancreas that are key for maintaining BG?
Insulin
Glucagon
What are the 2 broad components of the pancreas?
Endocrine
Exocrine
Where are endocrine hormone produced in the pancreas?
Islets of Langerhans
How does the pancreas release its exocrine chemicals?
Into ducts
What are the 4 types of islet cells?
Alpha
Beta
Delta
F cells
What do alpha islet cells produce?
Glucagon
What do beta islet cells produce?
Insulin
What do delta islet cells produce?
Somatostatin
What do F islet cells produce/?
Pancreatic polypeptide
What type of hormone is insulin?
Peptide
What does insulin stimulate?
Glc uptake by cells
How is insulin synthesised?
Synthesised as large preprohormone called preproinsulin
Converted to proinsulin in ER
Proinsulin is then packaged into vesicles
Within these is cleaved again to insulin and C peptide
Stored in this form until the B cell is activated and releases it
What is the major stimulus of insulin release?
Increase in BG conc.
Which is the only hormone to lower BG?
Insulin
Where is excess glucose stored?
In the liver as glycogen
What is excess Amino acids converted to?
Fat
What are amino acids used to make?
Proteins
What are FA stored in the form of in adipose tissue and the liver?
TAG
Describe the activation of beta cells to secrete insulin by glucose
High glucose in the blood
Enters the beta cell through GLUT transporter
ATP increases
Katp channels close
Cell depolarises and calcium channels open
Ca2+ entry acts as an intracellular signal
Ca2+ signal triggers exocytosis and insulin is secreted
Describe the effect of low BG on beta cell activation
BG is low ATP in the cell remains low Katp channels remain close so K+ ions flow out hyperpolarising the cell Ca2+ channels remain closed Insulin is not exocytoses
Where does insulin bind?
To tyrosine kinase receptors on the cell membrane of insulin sensitive tissue
What is the effect of insulin binding to target cells?
Increase glucose uptake by these cells
What does insulin stimulate the mobilization of in the cekk?
GLUT-4 channels which reside in the cytoplasm of unstimulated muscle and adipose cells
What is the action of GLUT4 transporters hen activated?
Migrate to the cell membrane
Then able to transport glucose into the cell
What happens to GLUT4 transporters when insulin stimulation stops?
It returns to the cytoplasmic pool
Which tissues are insulin sensitive?
Only muscle and fat
In tissue other than muscle and fat how is glucose taken up?
Uptake is via other GLUT transporters which are not insulin dependent
Is the liver an insulin sensitive tissue?
No
How does the liver take up glucose?
By GLUT 2 transporters which are insulin independent
Down a concentration gradient
How does the presence of insulin affect glucose uptake in the liver?
Enhances the uptake of glucose by the liver
In the fasted state what does the liver do to increase blood Glc?
The liver synthesises glucose via glycogenolysis and gluconeogenesis
What are some additional actions of glucose?
Increases glycogen synthesis
Increases AA uptake into muscle promoting protein synthesis
Increases protein synthesis and inhibits proteolysis
Increases TAG synthesis in adipocytes and liver
Inhibits the enzymes of gluconeogenesis in the liver
Has a permissive effect on GH
Promotes K+ entry into the cell by stimulating the Na+/K+ ATPase
What is the half life of insulin?
5 minutes
What happens to insulin bound receptors when insulin action is complete?
They internalise by endocytosis and are destroyed
- some are recycled
Which stimuli increase insulin release
Increased BG Increased AA Glucagon (insulin is required to take up the glucose that is released by glucagon) Other hormones controlling GI secretion e.g CCK Vagal nerve activity
Which stimuli inhibit insulin secretion?
Low BG
Somatostatin
Sympathetic alpha effects
Stress
What does vagal activity stimulate the release of?
Major GI hormones
And insulin
Why is the insulin response to IV glucose less than the equivalent amount of glucose administered orally?
Because oral loading of the same dose increases amount of BG both by direct effect on Beta cells and by vagal stimulation of beta cells
Where is glucagon produced?
Alpha islet cells
What is the primary purpose of glucagon?
To raise BG
Where does glucagon mainly act?
On the liver
What does glucagon have the opposite action to?
Insulin
When is glucagon most active?
In the post-absorptive state
What type of receptors are glucagon receptors?
G couple receptors
What is the effect of glucagon binding to its receptor?
Phosphorylation chain is activated leading to:
- Increased glycogenolysis 2.increased gluconeogenesis (substrates: aa’s and glycerol (lipolysis))
- formation of ketones from fatty acids (lipolysis)
Where does glycogenolysis, gluconeogenesis and lipolysis occur?
In the liver
When does glucagon release increase dramatically?
When Bg <5.6 mM
What else are a potent stimulus for glucagon secretion?
Amino acids
What is the effect of increases BG on insulin and glucagon?
Increased insulin
Decreased glucagon
What is the effect of decreased Bg on glucagon and insulin?
Increases glucagon
Decreases insulin
Do amino acids stimulate the release of insulin or glucagon?
Both
Which stimuli promote glucagon release?
Low Bg High AA Sympathetic innervation Cortisol Stress
Which stimuli inhibit glucagon release?
Glucose
Free FA and ketones
Insulin
Somatostatin
Why is insulin and glucagon released with high AA?
To counteract blood glucose getting to low with the effects of insulin
What is the effect of parasympathetic activity (vagal) on insulin?
Increases the release of insulin
Rest and digest `
What is the effect of sympathetic activity on insulin?
Inhibits insulin
Increases glucagon - promoting glucose mobilisation
What type of hormone is somatostatin?
Peptide
Which cells secrete somatostatin?
Delta islet cells
What is the pain pancreatic action of somatostatin?
To inhibit the activity in the GI tract
What is the effect of somatostatin on insulin and glucagon?
To suppress the release of both
Is SS a counter regulatory hormone in the control of Bg?
No
What is the effect of exercise on Bg?
The entry of glucose into skeletal muscle is increased
How does exercise decrease BG?
Increases the sensitivity of insulin receptors
Causes insulin independent increase in GLUT 4 transporters art the membrane
Describe glucose intake in an active muscle?
GLUT 4 transporters can migrate to the membrane without insulin being present
Increasing glucose uptake
After a period of starvation how does the brain adapt to get energy?
It adapts to be able to use ketones
What happens to tissue during starvation?
FFA can be released and used by most tissues to produce energy
Broadly what is DM?
Loss of control of BG levels
What are the 2 types of DM?
Type I
Type II
What is the pathophysiology of type I DM?
Autoimmune destruction of Beta cells destroy the ability of the pancreas to produce insulin
What is the treatment for type I diabetes?
Insulin injection
What type of need to type I DM patients have for insulin?
Absolute need
What is ketoacidosis in type I DM?
DKA occurs when the body has insufficient insulin to allow enough glucose to enter cells
The body switches to burning fatty acids and producing acidic ketone bodies.
This can quickly lead to life threatening acidosis
What is the pathophysiology of type II DM?
Peripheral tissues become insensitive to insulin
Insulin resistance
What can cause a decrease in response to insulin in type II DM?
Due to abnormal response of insulin receptors
Or a reduction in their number
What is type II DM commonly associated with?
Obesity
What is the initial treatment for Type II?
Exercise and diet change
Oral hypoglycaemic drugs
What are the 2 main oral hypoglycaemic drugs administered?
Metformin
Sulphonylureas
What does oral hypoglycaemic drugs require?
Functioning beta cells
What is hyperglycaemia?
Elevated BG
What is the diagnostic criteria for DM?
Hyperglycaemia
What is the first test for DM?
Glucose tolerance test
What is indicative of DM in a GTT?
BG is still elevated after 2 hours
What are some of the long term consequences of hyperglycaemia?
Retinopathy
Neuropathy
Nephropathy
Cardiovascular Disease (due to atherosclerosis)
What can the end stage complication of hypoglycaemia be?
Hypo coma
Death
