Background to DM Flashcards
What centres in hypothalamus determining energy intake
Feeding centre
Satiety centre
What does feeding centre do and how
Promotes hunger
Leptin = peptide hormone released by fat in adipose tissue
Decreases feeding activity
What does satiety centre do and what are theories behind
Promote feeling of full
Glucostatic - as BG increases, drive to eat decreases
Lipostatic - as fat increases, drive to eat decreases
What determines cellular output
Cellular work / metabolism
Mechanical work / movement
Heat loss = 50%
What is anabolism
Synthesis of larger molecules for stage
What state are you in after eating
Anabolic state (Absorption) Nutrients supply energy which is stored
What hormone dominates anabolic state
Insulin
What is catabolism
Breakdown of large molecules to release energy
What state are you in between meals
Catabolic (post-absorptive) Rely on stores to provide energy Glycogenolysis from glycogen Gloconeogenesis from AA / FA Ketogenesis
What hormone dominates catabolic state
Glucagon
What catabolic steroids are prescribed in. medicine
Glucocorticoid
What do most cells use for energy
FA
CHO
Protein - AA
What does brain use
Can ONLY use glucose
Uses ketones in extreme starvation
What happens in absorptive state
Glucose, AA and FA enter blood from GI tract
Glucose and AA stimulate insulin
What is the only hormone to lower BG
Insulin
What is main energy source in body
Glucose
What is excess glucose stored as and where
Glycogen in liver and muscle by glycogenesis
Stores are limited so if excess then glucose converted to fat
How is fat / FFA stored
TAG in adipose tissue by lipogenesis
What is lipolysis
Breakdown of TAG to release FFA and glycerol
FFA used as energy
Glyceral goes to liver and converted to glucose
What happens if excess FFA breakdown
Converted to ketone
What are AA used for
To make new proteins
Can be used to make glucose in extreme starvation
What do 4 islet cells (A,B,delta,F) of pancreas produce
A = glucagon B = insulin Delta = somatostatin (GHIH) F = pancreatic polypeptide
What does insulin promote
Lipogenesis Glycogenesis Protein synthesis Inhibits lipolysis and glucogenesis Reduces muscle protein loss Increases cellular uptake of K Permissive to GH
What is insulin
Peptide hormone stimulating uptake of glucose in liver, skeletal muscle and fat tissue
Where is it stored
Stored in vesicles as proinsulin in RER
Cleave to insulin and C peptide when needed
What causes release of insulin
B cells of pancreas activated when high BG Glucose enters through GLUT Provides energy so ATP created Causes Katp channel to close Intracellular K rises Cell depolarises Voltage gated Ca channels open Triggers insulin exocytosis
What happens when insulin becomes low
ATP levels low as no glucose
kATP channels open and K leaks out
Hyperpolarises cell
Ca channels close
What stimulates insulin release
Increased BG = main stimulus Increased AA Glucagon (insulin needed to take up glucose produced) Other GI secretion hormones Vagal nerve
What GI hormones
Gastric Secretin - acid in duodenum CCK - fat in duodenum GLP-1 Prevents glucose surge
Why does oral glucose cause larger increase in insulin than IV
Stimulates GI hormones and vagal nerve
GLP-1 in small intestine
Incretin effect
What stimuli inhibit release
Low BG
Somatostatin (GHIH)
Sympathetic A2
Stress e.g. hypoxia
What happens if no insulin
Cell’s unable to take up glucose as believe there is none
Leads to increased production of glucose by liver
Further increases BG
How does insulin promote glucose uptake and glycogen synthesis
Binds to receptors on insulin sensitive tissue - liver, muscle + adipose
Stimulates mobilisation of GLUT 4 transporters so glucose transported into cells
What is only insulin dependent tissue
Muscle
Adipose
What happens if you remove insulin
Can get hyperkalaemia as K not taken up into cell
What is glucose in other tissue dependent on
Brain / kidney / RBC = Glut 1+3
B cells / liver = glut 2
How does glucose enter if not by insulin
Travels down conc gradient
What happen in the liver
Not insulin dependent but helps
Insulin activates hexokinase lowering glucose conc as converts to glucose 6 phosphate
If fasted liver synthesis glucose via glycogenolysis and gluconeogenesis increasing conc and glucose moves out
What is glucagon and where is it produced
Peptide hormone
Alpha cells of pancreas
Acts mainly on liver and degraded there
What are glucagon receptors on tissue
G-protein coupled receptor
Linked to AC / cAMP
What happens when receptors phosphorylated by glucagon
Increased glycogenolysis in liver
Increased gluconeogensis of AA and glycerol (from lipolysis)
Ketogenesis from FFA
Lipolysis
What does glucagon not act on
Muscle
What hormones form glucose counter regulatory control
Epinephrine (Adrenaline)
Cortisol - glucose needed in stress
GH
What does epinephrine cause
Muscle glycogenolysis
Liver glycogenolysis and gluconeogensis
Lipolysis
What does cortisol do
Liver gluconeogensis
Lipolysis
Protein catabolism so AA can be used
Inhibits uptake of glucose
What does GH do
Liver gluconeogensis
Lipolysis
Inhibits uptake
What must the body always ensure
Enough glucose for brain as other tissues can use FFA
What promotes release of glucagon
Low blood glucose High AA Sympathetic Cortisol Stress
Why does high AA stimulate insulin and glucagon
Prevents hypoglycaemia following insulin release in response to AA
What stimuli inhibit release of glucagon
Glucose
FFA / ketones
Insulin
Somatostatin
What is somatostatin
Peptide hormone produced by D cells of pancreas and hypothalamus
Inhibits glucagon and insulin
What is it stimulated by
High blood glucose
High AA
What is the role of somatostatin
Inhibits activity of GI
Slows absorption to prevent exaggerated peaks
Inhibits secretion of GH
Suppress insulin and glucagon in paracrine fashion
NOT counter regulatory
What do patients with pancreatic SS secreting tumours develop
Sx of DM
What can synthetic SS be used to treat
Life threatening diarrhoea due to tumours as slows absorption
How does ANS parasympathetic (vagus) nerve affect diabetic hormones
Increases insulin
Increases glucagon to lesser extent
Associated with anticipatory phase of digestion
What does sympathetic nerve do
Inhibits insulin
Promotes glucose mobilisation
Increases glucagon and epinephrine
Fight or flight
What happens during exercise
Increase entry into skeletal muscle (even if no insulin)
Increased insulin sensitivity
increased insulin independent glut 3 transporter
What happens during starvation
Body relies on glucose stores
Adipose borken into FFA which can be used by most cells
Converts FFA to ketone body so brain can use
Spares protein
What happens if underlying pathology not starvation
Metabolic acidosis = DKA
If extreme hyperglycaemia as no insulin so cells believe there is no glucose
What slows absorption of glucose
Fat so if hypo don’t give fatty food
