Where is pancreas and what does it look like?
In abdominal cavity (head and neck in C-shaped curve of the duodenum and the body extends behind stomach)
-Islets - independent endocrine organ (not under hypo/pit axis)
-Pancreas releases insulin and glucagon which controls glucose
Pancreas - an _____ gland and an _____ gland
1. What does each contain?
2. Where are beta and alpha cells found?
Pancreas - an exocrine gland and an endocrine gland
1. Refer to diagram
2. Alpha and beta found in pancreatic islet
Constant glucose levels (memorise)
-Insulin signals to cells in body to take up glucose or stimulate glycogen formation in liver
-glucose levels high when at and low when fast
-Glucagon = increase glucose when glucose gone
-Insulin = decrease glucose when we take in glucose
-glucagon binds to receptors on liver cells and stimulates breakdown of glycogen
1. Fasting levels
2. Within 2h postprandial:
3. But within hours of the meal.......
Fasting levels: 60-80 mg/ dL (3.3-4.4 mM)
Within 2 hours postprandial: 100-140 mg/ dL (5.6-7.8 mM)
But within hours of the meal BGL returns and is maintained at homeostatic levels
Insulin regulates fuel storage
-Insulin tells cells to remove glucose from bloodstream
-It's the only hormone that's able to stimulate cells to remove glucose (GH etc all increase it)
-Insulin is dissolved in blood bc it's a protein hormone
-It will go through mechanism by which insulin activates glucose transport into cells
-Target cells: muscle - skeletal muscles either convert glucose to glycogen or use it if active at the time
-Target cells: fat - convert it to tri-glycerides and stores it as fat
-Negative feeback when it's falled back to homeostatic levels
Glucagon: regulates fuel storage
-Glucagon is peptide hormone
-Insulin is the only one that lowers glucose levels
-Blood ketones - can be used by brain as energy course; glucagon provides another food source for brain if starvation was to continue
Integration–Hormonal Control of Blood Glucose
Protein mobilisation - aa' increase
Protein hormone - dissolves in blood. Binds to its specific receptor - signals a cascade which leads to opening of glucose channels on the membrane of those cells.
When channels open - glucose travels into cells (2ndary messenger)
Glucose uptake and glycogen synthesis (muscle)
-No insulin; no glucose inside cell bc no activation of glucose channels
-GLUT4; translocate to plasma membrane when PI-3 kinase binds to these stores - form channel and allow glucose to come inside cell
-G6P; generate ATP for muscles where active at time
-Glycogen; if muscles hv excess energy and not active at time, bloog glucose needs to be lowered
-That yellow this is a vesicle that stores GLUT4 and these are the glucose transporters
Insulin resistance - high blood sugar
-Make a whole lotta insulin but it's not acting to promote the moving of glu chann so glucose lvls stay high (and we'll hv high insulin lvls)
-Western society = eating lots of saturated fats and we hv lots of glucose in diet (junk food) - often we hv high lvls of sugar so we hv high lvls of insulin and bc intake of sat fat in diet, we hv high lvl of fatty acids - this combination leads to insulin resistance
Insulin Resistance (muscle): Lipid Accumulation
-FA, activates pathway which increase diacylglycerol ----> this pathway switches off glucose pathway.
-Glucose transporters not being moved if no insulin and if we have high lvls of FA (fatty acids) in blood stream for long period of time - this dia is an inhibitor of phosphorylation process
-Precursor to developing type II diabetes
-We hv exhausted our beta cells by making them produce insulin heaps to try and lower glucose lvls but can't lower them bc we have FA dia shutting it off.
-Constant high lvl of glucose leads to beta cells increasing in sie until eventually the whole mechanism shits down B cells and no more insulin
-So we start to produce less and less insulin - can turn into type 1 diabetes (? check that)
Long term insulin resistance leads to impaired β-cell function
-B cells trynna compensate and lower blood glucose lvl ---> cells wont respond to insulin bc fatty acids in blood leads to dia pathway which stops glucose pathway
History of insulin
Insulin: first extracted by Banting & Best in 1921. Banting and supervisor/mentor McLeod received the Nobel Prize for Medicine in 1923 for the discovery of insulin.
So what was the experiment?
Remove pancreas – dog develops diabetes. Ligate duct – no diabetes.
Remove pancreas, freeze and filter.
Inject pancreatic extract into a diabetic dog – blood glucose dropped.
Collip joined group & purified insulin (from cow) for human testing. Banting and Best were first ‘patients’.
-Ligate duct is exocrine fucntion
-These two found glucose conc decreased at the end
First patient treated with insulin
Leonard Thompson, a 14-year-old diabetic admitted to Toronto General Hospital, was the first patient to be treated with crude preparations of insulin.
"On admission he was poorly nourished, pale, weight 29.5 kg, hair falling out, odour of acetone on the breath ... He appeared dull, talked rather slowly, quite willing to lie about all day."
There was a striking decrease in blood glucose concentration following the injection of pancreatic extract. With continued administration of crude insulin, "the boy became brighter, more active, looked better and said he felt stronger."
-Nowadays, use recombinant insulin from technologies
Type I diabetes mellitus (~10% of diabetics)
2. When diagnosed?
5. Treatment is?
1. Symptoms: high blood glucose (hyperglycemia), glucose in urine (glycosuria), large urine volumes (polyuria), thirst (polydipsia). Also hunger (polyphagia).
2. Normally diagnosed during childhood.
3. Cause: Insulin-producing beta cells have been destroyed (autoimmune disease), and insulin levels low/zero.
4. Remember – insulin is the only hormone that can reduce blood glucose!
5. Treatment is insulin injections.
-Pancreatic B cells gone so insulin down bc B cell is the only cell that produces it
-So need exogenous suuply of insulin
-Zero insulin pre much
Type II diabetes mellitus
1. Used to be adult disease - now is what?
2. Cells are resistent to?
3. Treatment includes?
4. Risk factors include?
5. Research at UoO shows?
• Used to be an adult disease, now being diagnosed in children.
• Cells are resistant to insulin’s signal to store fuel eg. fewer receptors. Insulin level is also lowered.
• Treatment includes insulin injections, drugs promoting insulin release such as incretins.
• Risk factors include obesity, certain ethnicities and inherited genetic changes.
• Research at UoO shows lifestyle changes (dietary changes of reduced fat/increased protein, and more exercise) can reduce hyperglycaemia for type II diabetics already on drug treatment.
-Very much life-style and diet dependent
-severe = B cells exhausted (hypertropheiu?) to making any insulin - treatment else reversible (I think?)
-C cells are still producing insulin (can reverse by lowering FA in bloos and eating better and exercising - can restore insulin resistant state
-Low amounts of insulin still produced but FA stops pathway so that little bit of insulin doesn't act
-Cells are insulin resistant (can't take glucose in