The Peripheral Endocrine Glands Lecture 8 - hormones secreted by pancreas Flashcards
Beta cells
- 60%
- site of insulin synthesis and secretion
- located centrally in islets
Alpha cells
- 25%
- produce glucagon
delta cells
- 10%
- pancreatic site of somatostatin synthesis
F cells
- 1%
- least common islet cells
- secrete pancreatic polypeptide (PP)
- reduce appetite and food intake
Connective tissue, blood vessels and nerves
- 4%
Epsilon cells:
secrete Ghrelin
Somatostatin is produced by
- delta-cells in pancreas
- hypothalamus (aka GHIH) – inhibits secretion of GH
Somatostatin
Stimulus for secretion:
increased blood sugar and blood amino acids during absorption of a meal
Somatostatin functions:
decrease digestion and absorption of nutrients
Prevents excessive plasma levels of nutrients
Presence of somatostatin - decrease secretion of insulin, glucagon, and somatostatin itself
Insulin:
Decreases blood glucose, fatty acids & amino acids – promotes their storage
During absorptive state:
(just after a meal)
- Most NB time for insulin
- insulin promotes cellular uptake of blood glucose, fatty acids & amino acids and their conversion into glycogen, triglycerides and protein
Insulin exerts its effects through:
- increased activity of glycogen synthase (glucose –> glycogen)
= glycogenesis - decreased activity of hormone sensitive lipase
(triglycerides –> free fatty acids and glycerol)
Circulating glucose concentrations are determined by:
Action of insulin on blood glucose levels and storage of carbohydrates
insulin:
- Facilitates glucose transport into most cells
- increases glycogenesis (glucose –> glycogen) in skeletal muscle and liver
decrease glycogenolysis (glycogen –> glucose)
decrease hepatic glucose output by decreasing gluconeogenesis (amino acids –> glucose)
Glucose transport into cells
- Transport between blood and cells – plasma membrane carrier, glucose transporter (GLUT)
- 14 forms
- Passive facilitated diffusion across plasma membrane
- Inside cell glucose is P to glucose-6-phosphate –> glucose is trapped inside the cell, also keeps [ ] of plain glucose inside cell low – gradient favouring facilitated diffusion of glucose into cell
- Family members of GLUT family performs different functions
GLUT-1:
transport glucose across blood-brain barrier
GLUT-2:
transfer glucose that has entered the kidney and intestinal cells into adjacent bloodstream by means of sodium and glucose co-transporter.
GLUT-3:
transport glucose into neurons
GLUT-4:
abundant in tissues that account for the bulk of glucose uptake in the absorptive state – skeletal muscle & adipose tissue
GLUT-4 is the only glucose transporter that responds to insulin
- Why?
- these organs are responsible for highest uptake of glucose for storage, thus must respond to insulin
- No insulin, no GLUT-4 in plasma membrane
- Intracellular vesicles contain GLUT-4
- When insulin binds to receptor (phosphorylated tyrosine kinase) on surface membrane of target cell, vesicles moves to plasma membrane, fuse with it and inserting GLUT-4 on membrane
- Decrease in insulin – glucose transporters are retrieved from membrane by endocytosis, returned to intracellular pool
Brain, working muscles and liver _______ depend on insulin for glucose uptake
DO NOT
Brain, working muscles and liver DO NOT depend on insulin for glucose uptake
Brain:
requires constant supply of glucose – freely permeable to glucose at all times – GLUT-1 & GLUT-3
Brain, working muscles and liver DO NOT depend on insulin for glucose uptake
Skeletal muscle
depend on insulin ONLY at rest for glucose uptake
Muscle contraction triggers insertion of GLUT-4 on plasma membrane
Brain, working muscles and liver DO NOT depend on insulin for glucose uptake
Liver
does not depend on insulin for glucose uptake; does not use GLUT-4
Insulin enhance the metabolism of glucose by liver through P glucose to glucose-6-phosphate
Action of insulin on FAT
- increase fatty acids into adipose tissue
- increase glucose into adipose tissue through GLUT-4 recruitment
- Promotes chemical reactions that use glucose and fatty acids derivates for triglyceride synthesis
- decreases lipolysis (fat breakdown)
THUS: favouring removal of fatty acids and glucose from blood, promotes their storage as triglycerides
Actions of insulin on PROTEIN
- increase active transport of amino acids from blood into muscle and other tissue – provides building blocks for protein synthesis
- increase rate of amino acid incorporation into protein – stimulating cell’s protein-synthesizing machinery
- Inhibits protein degradation
THUS: protein anabolic effect – essential for normal growth (permissive to GH).
Glucose stimulates insulin secretion through excitation-secretion coupling process NB
Must be able to draw and explain!
- high levels of glucose are detected by the beta cells of the pancreas
- these beta cells then take up the glucose via the GLUT-2 transporter
- this will increase the intracellular glucose levels
- this glucose is then phosphorylated to form G6P
- it will then be oxidised and ATP will be formed
- ATP responsible for closure of ATP sensitive potassium channels
- this results in an increase in intracellular potassium levels, which causes depolarization of the membrane of the cell
- this then opens up the voltage-gated calcium channels and calcium will enter the cells
- high levels of calcium in the cells will be responsible for the exocytosis of the vesicles which are filled with insulin
inputs for insulin secretion:
- high blood glucose levels
- increase in blood amino acid level - induces insulin secretion in the same way as glucose - by generating ATP, which leads to excitation-excretion coupling
- gastrointestinal hormones (incretins)
incretins - consist of GIP (Glucose-dependent insulinotropic peptide) and GLP (glucose-like peptide)
the secretion of these hormones will notify the Beta cells (stimulated by food intake)
Most common of all endocrine disorders
Diabetes Mellitus
Diabetes Mellitus Prominent features:
elevated blood glucose levels
Urine acquires sweetness from excess blood glucose that spills into urine
Type I diabetes
Characterized by lack of insulin secretion
Type II diabetes
Characterized by normal or even increased insulin secretion but reduced sensitivity of insulin’s target cells
https://www.youtube.com/watch?v=JAjZv41iUJU
3 P’s of Diabetes
- polydipsia: extreme thirst
- polyuria: frequent urination
- polyphagia: hunger
NB diagram!!
Diabetic person can lose consciousness and die from:
diabetic ketoacidotic coma due to insulin deficiency (deep laboured breathing and fruity breath)
acute hypoglycemia caused by insulin shock
Insulin excess hypoglycemia is caused by:
In diabetic patient when too much insulin is injected – insulin shock
Consequences:
- More glucose than necessary is driven into insulin-dependent cells
> decrease blood glucose, brain starves, depressed brain function, unconsciousness, death.
Treatment: Immediately eat or drink something sugary
Insulin excess: hypoglycemia
Reactive hypoglycemia is caused by:
B-cell tumours: secreting increased insulin
B-cells: over-responsive to glucose
Consequences: tremor, fatique, sleepiness, inability to concentrate (non-specific)
Treatment: limit sugar and carbohydrate intake
What will be the metabolic effects in a diabetic persons under stress conditions?
- look at metabolic effect of cortisol and epinephrine
(stress hormones) - both these hormones increase blood glucose levels
- diabetic person already has elevated blood glucose levels, which is now further aggravated by these stress hormones
- must inject a little bit higher level of insulin to regulate blood glucose levels
NB: Study this summary of the metabolic effects of the different hormones and the control of secretion
