L46 - Glucose Homeostasis Flashcards
What are the cell types that secrete hormones in the pancreas?
- islets of langerhans
- a-cells - glucagon
- B-cells - insulin
- delta-cells - somatostatin (supress release of insulin and glucagon)
What type of signalling do islets show?
- paracrine
- endocrine signalling
What does insulin do?
- decreases plasma
- glucose
- a/a
- FFAs
- (anabolic)
What does glucagon do?
- increase plasma
- glucose
- ketones
- (catabolic)
What is the structure of insulin?
- B-chain - biologically active
- A-chain - “
- C-peptide - inactive
What is insulin degraded by?
- insulin
- in liver and kidneys
How is insulin secreted in response to changes in glucose/ATP?
- [g] inc
- glucose converted to glucose-6-phosphate
- glycolysis to ATP in mitcochondria
- ATP/ADP inc in cell
- ATP sens KC detects this
- depolarisation causes VGCC to open
- Ca2+ enters cells
- Ca2+ causes vesicles to release insulin to blood
What are plasma insulin concentration like in the different states?
- inc during absorptive state
- dec during postabsorptive state
What is insulin secreted by? And occurs by?
Calcium-dependent exocytosis from B-islet cells in response to high levels of glucose
What does insulin have to do to induce its effects?
Must bind to specific receptors on plasma membrane of target cell
What is insulin binding like?
- dimerisation
- receptor tyrosine kinase
- autophosphorylation
- effects on intracellular kinase/phosphatases
- effects on key enzymes
What are the actions of insulin?
- carbohydrate metabolism
- lipid metabolism
What is carbohydrate metabolism?
- facilitates glucose entry to muslce, adipose (GLUT)
- stimulates liver to store glucose as glycogen
- dec [glucose] in blood
What is lipid metabolism?
- promotes synthesis of FA in liver (when glycogen saturated)
- = in in lipoproteins in circulation to release FA (triglyceride synthesis in adipocytes)
- inhibits fat breakdown in adipose tissue
- promotes glycerol synthesis from glucose, inc triglyceride synthesis
How does insulin stimulate uptake of insulin?
- inc [glucose] causes insulin release
- binds to insulin RTK
- causes release of glucose transporters to absorb more glucose
What does insulin do on muscle cells?
- glucose and a/a uptake stimulated by insulin
- metabolised to glycogen or lactic acid (to liver)
- a/a to structural proteins
What do insulin sensitising drugs do on skeletal muscle?
Increase glucose utilisation
What does insulin do on liver cells?
- inc uptake of glucose, lactice acid, a/a, FA
- stimulates glycogen synthetase, glucokinase, glucose-6-phosphatase
- metabolised to glycogen or lipoproteins
What does insulin sensitising drugs do in liver?
Reduce gluconeogenesis
What does insulin do on adipose tissue?
- glucose, a/a, lipoproteins uptake stimulated
- metabolised to triglycerides
What does insulin do to restore homeostasis of blood glucose?
- inc rate of g uptake
- in g utilisation and ATP gen
- inc glycogenesis
- inc protein synthesis
- inc fat synthesis
What is glucagon? What is it released from?
- peptide hormone 29AA
- released froma-cells of islets when [glucose] falls
What does glucagon do to restore homeostasis on blood glucose?
- inc glycogenolysis
- inc fats to FA
- inc protein breakdown
- inc gluconeogenesis
What is hypoglycaemia?
- blood glucose < 3mM
- uptake of glucose by dependent tissue not adequate to maintain tissue function
What does hypoglycaemia do to CNS?
- impaired vision
- slurred speech
- staggered walk
- mood change
- confusion
- coma
- death
What does hypoglycaemia do to ANS?
- palpitations
- sweats
- shakiness
- hunger
What is hyperglycaemia?
- diabetes mellitus
- fasting blood glucose > 7 mmol/L
- type 1 - genetics
- type 2 - diet and lifestyle
- gestational - pregnancy - transient
