Control of Metabolism & Biochemistry Flashcards
Which centres of the hypothalamus determine energy intake?
2
Feeding centre Satiety centre (insulin sensitive)
Which 2 theory’s describe food intake drive?
Glucostatic (Blood Glucose Levels)
Lipostatic (Leptin peptide hormone being released from fat stores decreases feeding)
What are the 3 classes of energy output?
Cellular work - Metabolism
Mechanical work - Movement / moving neurotransmitters
Heat loss - Associated with both above
Anabolic pathways
Synthesis large molecules
Catabolic pathways
Break down larger molecules
How is glucose synthesised
Glycogen (glycigenisis) Amino acids (gluconeogensis)
What is the normal blood glucose range
4.2-6.3mM
Which are the 2 main hormones involved in the regulation of blood glucose levels
Insulin & Glucagon
What percent of the pancreas has endocrine function?
1% (Islets of Langerhans)
Whats are the cell types in Islets of Langerhans and what do they produce?
Alpha - Glucagon
Beta - Insulin
Delta - Somatostatin
F - Pancreatic polypeptide
What are the actions of Insulin dominance over Glucagon?
(High Blood Glucose Levels)
(4)
Increase in:
- Glucose oxidation
- Glycogen synthesis
- Fat synthesis
- Protein synthesis
What are the actions of Glucagon dominance over Insulin?
(Low Blood Glucose Levels)
(3)
Increase in:
- Glycogenolysis
- Gluconeogenesis
- Ketogenesis
What type of hormone is Insulin
Peptide
What is used to measure beta cell function (inline production)?
C-Peptide Levels
What hormone other an insulin lowers blood glucose levels?
None
How can glucose be stored?
Glycogen in the liver
Triacylglycerols in liver and adipose tissue
What are the mechanisms of control of insulin secretion?
Increase of Blood glucose
Increases in glucose entering beta cells (GLUT)
Increase in metabolism
Increase in ATP
K+ ion channels in he beta cells are sensitive to ATP so close
Cells depolarise
Volted gated Ca channels open
Ca enters the cell triggering exocytosis of vesicles
Insulin is released
What receptors does insulin bind to on muscle and adipose tissue?
Tyrosine Kinase Receptors
What is the action of insulin binding to surface receptors
GLUT-4 transporters migrate from the cytoplasm to the cell membrane and becomes imbedded for the transport of glucose
How does the GLUT-4 transport become attached to the cell membrane?
Insulin binds to receptors
Intracellular signalling cascade
GLUT4 migrates to membrane
GLUT-4 exocytosis into the cell membrane
Glucose enters the cell down the concentration gradient
How do muscle and adipose tissues take up insulin in the absence of insulin?
Adipose - Can’t
Muscle - Can’t at rest but during exercise GLUT-4 transporters migrate independently of insulin
Which tissues are insulin dependant?
Muscle (40% of body weight)
Fat (20-25% of body weight)
What do other cells use to transport glucose?
Non insulin dependant GLUT transporters
What cells use GLUT 1,2 & 3 transporters
GLUT-1 = Brain, Kidney, RBCs and other tissues GLUT-2 = Beta cells of pancreas & Liver (insulin can still help in liver) GLUT-3 = Similar to GLUT-1
How does insulin help the hepatocytes absorp glucose ?
Insulin stimulates hexokinase in liver cells
Signalling cascade
Tuns glucose into Glucose-6-phosphate
This reduces the concentration of glucose inside the cell
Increases the concentration gradient
More glucose enters the cell
What are the additional actions of insulin?
Anabolic:
Increases glycogen synthesis in muscle and liver cells
Increases amino acid uptake (protein synthesis)
Inhibits proteolysis (protein metabolise)
Increases triacylglycerol synthesis in adipocytes
Inhibits gluconeogenesis in the liver
Hormones:
Has a permissive effect on growth hormone
Promotes K+ ion entry
How does insulin increase glycogen synthesis?
Stimulates glycogen synthase and inhibits glycogen phosphorylase
How long is Insulins half life?
5mins
Where is Insulin broken down and by what?
Insulin bound receptors internalised by endocytosis and destroyed by insulin protease
Insulinase in liver and kidneys
What increases insulin release?
Increased BG Increased Amino Acids Increased Glucagon (for the uptake of glucose following gluconeagenisis) GI secretion & motility (CCK & secretin) Vagal nerve
What inhibits insulin release?
Low BG
Somatostatin
Sympathetic alpha effects*
Stress (hypoxia)*
*results of the sympathetic nervous system
Why is more insulin released as a result of oral glucose rather than IV glucose intake?
Vagus + Incretin response on top of the usual direct effect on Beta cells
What is the half life of Glucagon?
5-10mins
Where are most Glucagon using cells found?
Liver
What are the Glucagon receptors?
G-Protein coupled receptors
What would the brain switch to in the absence of Glucose?
Ketone Bodies
What are the three processes caused by Glucagon?
- Glycogenesis (break down of Glycogen)
- Glucaneogenasis (break down of amino acids)
- Ketosis (Breakdown of adipose tissues)
What would happen if Glucagon wasn’t secreted in a rise of amino acids?
Insulin would rise to absorb amino acids
Glucose would also be absorbed
Hypoglycaemia would occur
What are the 4 hormones which respond to a low Blood glucose level?
Glucagon - Glycogenolysis (liver)
Epinehrine - Glycogenolysis (liver and muscle)
Cortisol - Protein catabolism & Inhibition of glucose uptake
Growth Hormone - Inhibition of glucose uptake
All promote Lipolysis & Gluconeogensis
What is the main function of Somatostatin?
Inhibits activity in GI tract (slows down gastric motility absorption of nutrients)
Inhibits alpha and beta cells from secreting insulin and glucagon
How does exercise effect insulin sensitivity?
Increases sensitivity for several hours post exercise
