Diabetes Flashcards
What is glucose?
Ubiquitous energy source stored as glycogen in the body
What are the types of glycaemia and what are the defined levels?
Hypoglycaemia <2.5mmol/L
Fasting normoglycaemia 3-5mmol/L
Post-prandial normoglycaemia 7-8mmol/L
Hyperglycaemia >10mmol/L (sustained)
Describe the homeostasis of hyperglycaemia
Blood glucose rises after food intake or glycogenolysis in the liver
Pancreatic beta cells release insulin
Insulin acts on liver, muscle cells, adipocytes and CNS to increase glucose uptake
Blood glucose returns to normal
Describe the homeostasis of hypoglycaemia
Blood glucose falls following fasting or overnight fast
Pancreatic alpha cells release glucagon
Glucagon acts on liver, muscle cells and adipocytes to stimulate conversion of glycogen to glucose
Blood glucose returns to normal
How is proinsulin converted to insulin?
23 amino acids removed (C-peptide subunit) - leaves A and B chains
Where is insulin produced and stored?
Beta cells of islets of Langerhans
Stored in secretory granules as a crystal structure (complex with zinc)
What is the half life of insulin?
3-5 minutes
Where is insulin metabolised?
The liver
Describe the physiology of the islets of Langerhans
Clusters of alpha, beta, delta, epsilon and pancreatic polypeptide cells
Innervated and vascularised
What hormones are released from the pancreas? What are their functions?
Insulin and glucagon - blood glucose control
Somatostatin and ghrelin - control of growth hormone production, increase appetite and fat storage
Pancreatic polypeptide - Regulation of pancreatic secretions
How is insulin released?
Glucose taken up by beta cells
K-channels close causing depolarisation
Ca2+ channels open
Influx of Ca2+ causes release of insulin from granules
Gut hormones (e.g. GLP-1) released into blood, activation of receptors of beta cells results in insulin release
How does insulin reduce blood glucose?
Increased GLUT-4 presence and activity to increase glucose uptake
Decreased breakdown of glycogen
Increased fat storage and protein production (to make more insulin)
What are the homeostatic mechanisms for blood glucose control in the CNS?
Increase/decrease appetite
Increase/decrease energy use
What are the homeostatic mechanisms for blood glucose control in the GI tract?
Increase/decrease glucose uptake from food
Incretins secreted from GI tract in response to nutrient ingestion, stimulates insulin production in beta cells
What are the homeostatic mechanisms for blood glucose control in the liver?
Increase/decrease endogenous glucose production
Increase/decrease glycogen storage
What are the homeostatic mechanisms for blood glucose control in the Islet cells?
Release of insulin and glucagon
What are the homeostatic mechanisms for blood glucose control in the kidney?
Increase/decrease loss of glucose through reabsorption
What are the homeostatic mechanisms for blood glucose control in the skeletal muscle?
Increase/decrease glucose uptake and utilisation
What are the homeostatic mechanisms for blood glucose control in the adipocytes?
Increase/decrease lipolysis and glucose uptake
Increase decrease leptin
What is the function of leptin?
Signals to hypothalamus when enough fat is stored so appetite is reduced - calorie regulation
What is diabetes?
Hyperglycaemia as a result of little/no insulin production or decreased insulin sensitivity
What are the therapeutic targets for diabetes treatment?
Promoting excretion of glucose through kidneys
Delay glucose absorption from GI tract
Promote insulin release from islet cells
Sensitise targets to endogenous insulin
Replace islet cells
What are the non-medical causes of hypoglycaemia?
Irregular/insufficient food intake
Insulin overdose
Sulfonylurea overdose