Lecture 4 The Endocrine Pancreas 1&2 Flashcards
Define Glucostatic Theory
Food intake is determined by blood glucose. As BG increases the drive the eat decreases
Define Lipostatic Theory
Food intake is determined by fat stores, as fat stores increase the drive to eat decreases. Leptin is a peptide hormone released by fat stores to depress feeding activity
Which energy output can the human body egulate
Mechanical work as it is voluntary
What is the absorptive state
Where ingested nutrients supply the energy needs of the body and the excess is stored (anabolic phase)
What is the Post-absorptive phase
Fasted State where we rely on body stores to provide energy (catabolic phase)
Why is the brain referred to as an obligatory glucose utiliser
Brain can only use glucose except in extra cases of starvation in which it uses ketones
What is the normal BG range
4.2-6.3mM (80-120mg/dl)
5mM
When is someone BG hypoglycaemic
<3mM
What are the 4 types of islet cells in the Islets of Langerhans
alpha cells produce GLUCAGON
beta cells produce INSULIN
delta cells produce SOMATOSTATIN
F cells produce pancreatic polypeptide
Describe how insulin goes from its active form to inactive
Preproinsulin
Proinsulin in ER
Proinsulin in cleaved in Golgi
Insulin and C-peptide
Excess glucose is stored as
Glycogen in liver
Triacylgycerides in liver and adipose tissue
Excess amino acids is stored as
Fat and form an energy source
Fatty acids are stored as
Triglycerides
Describe the mechanism of insulin secretion when glucose is abundant
Glucose enters cells through GLUT and metabolism increases
This increases [ATP] within the cell causing the KATP channel to close
Intracellular [K+ ] rises, depolarising the cell. Voltage-dependent Ca2+ channels open and trigger insulin vesicle exocytosis into the circulation.
Describe the mechanism of insulin secretion when glucose is low
ATP is low low so KATP channels are open so K+ ions flow out removing +ve charge from the cell and hyperpolarizing it, so that voltage-gated Ca2+ channels remain closed and insulin is not secreted.
Describe the primary action of Insulin
- Binds to tyrosine kinase receptors on the cell membrane of insulin-sensitive tissues to increase glucose uptake by these tissues
- Phosphorylates IRS
- Second messeger alter protein synthesis
- membrane transport modified
- Cell metabolism is changed
Where is GLUT 2 located
plasma membrane of the liver, pancreatic, intestinal, kidney cells
Where is GLUT 4 located
cytoplasm of muscle and adipose tissue cells. When stimulated by insulin GLUT4 migrates to the membrane and is then able to transport glucose into the cell. When insulin stimulation stops, the GLUT-4 transporters return to the cytoplasmic pool
What tissues are insulin dependent
Muscle and Adipose tissue
What tissue isn’t insulin dependent
Liver
Describe glucose uptake during the fed state in the liver
liver takes up glucose because insulin activates hexokinase which lowers [glucose]ic creating a gradient favouring glucose movement into the cells.
Describe glucose movement during the fasted state
liver synthesises glucose via glycogenolysis and gluconeogenesis, increasing [glucose]ic creating a gradient favouring glucose movement out of the cells into the blood.
What is the half-life of insulin
5 minutes
What happens to the insulin bound receptors once insulin action is complete
insulin-bound receptors are internalised by endocytosis
Name stimuli which increase insulin
High Blood glucose Amino acid Glucagon Incretin hormones Vagal nerve activity
Name stimuli which inhibit insulin
Low blood glucose
Somatostatin (GHIH)
Sympathetic
Stress e.g. hypoxia
Between IV and oral glucose which would have the largest insulin response
• Oral loading of same amount of glucose insulin by both direct effect on cells and vagal stimulation of cells, plus incretin effects
What type of hormone is glucagon
Peptide hormone and produced by 1-cells of the pancreatic islets cells
Glucagon mainly acts on what organ
Liver
What is the plasma half-life of glucagon
5-10 minutes and degraded by liver
Name the main actions of Glucagon
Opposes action of glucagon
Increased glycogenolysis
Increases gluconeogenesis
Formation of ketones from fatty acids
Following a meal rich in proteins why is there an increase in insulin and glucagon
The rise in amino acids stimulates insulin secretion which promotes an increase in amino acid uptake and promotes decrease in plasma glucose inappropriate and can lead to hypoglycaemia
• Rise in plasma amino acids also stimulates the secretion of glucagon which tends to promote an increase in plasma glucose
Stimuli that promote glucagon release
- Low blood glucose
- High amino acids to prevent hypoglycaemia
- Sympathetic innervation and adrenaline B2 effects
- Cortisol
- Stress e.g. exercise, infection
Stimuli that inhibit glucagon release
- Glucose
- FFA
- Insulin
- Somatostatin
Describe the parasympathetic stimulation of Islet cells
Insulin increase as well as glucagon in anticipation of digestion
Describe the sympathetic stimulation of islet cells
Increase in glucagon, epinephrine and inhibition of insulin
Name hormones that regulate muscle glycogenlysis
Epinephrine
Name hormones that regulate liver glycogenolysis
Glucagon
Epinphrine
Name hormones that regulate Gluconeogenesis
Glucagon
Name hormones that regulate inhibition of glucose uptake
Cortisol and GH
Name hormones that regulate lipolysis
Epinphrine
Name hormones that regulate protein catabolism
Cortisol
Somatostatin in secreted by what cell
D-cells of the pancreas and hypothalamus (GHIH)
What is the main actions of Somatostatin
Inhibit activity in the GI tracts
Slow down absorption of nutrients to prevent exaggerated peaks in plasma concentration
Supress release of insulin and glucagon in paracrine fashion
GHIH it inhibits secretion of GH from the anterior pituitary
What is the effect of exercise on blood glucose
Entry of glucose into skeletal muscle is increased. Even in the absence of insulin
Muscle sensitivity to insulin increases which causes an increase in insulin independent GLUT 4 transporters
What is the molecular weight of glucose
180
How do you work out the blood glucose in mM
Divide blood glucose after fasting by (180/18)
Name complications of diabetes
- Hyperglycaemia
- Retinopathy
- Neuropathy
- Nephropathy
- Cardiovascular Disease
