Diabetes Flashcards
How is glucose stored
As glycogen (when there is an abundance of glucose)
Glucose storage when maximum level of glycogen is reached
glucose still enters cells via GLUT4 but is broken down to fatty acids and stored as fats
where is glucose stored
liver (mainly) and muscles
mechanism of glucose homeostasis after a meal (4)
increased glucose absorption which may stimulate metabolism
increased glucose concentration in circulation
insulin is released
increased oxygen demand
mechanism of glucose homeostasis in between meals (4)
glucose absorption is minimal
which lowers glucose concentration in circulation
limited metabolism
decreased oxygen demand
What happens when glucose conc increased in blood (6)
increased glucose conc in beta cells of pancreas
= increased ATP conc produced by beta cells
high internal ATP = K+ channels close
= membrane potential is depolarised
= Ca2+ channels open
= beta cells secrete insulin
what is insulin produced by
beta cells
major target of insulin
liver
roles of insulin (4)
promotes uptake and storage of glucose
promotes synthesis of new proteins
promotes use of glucose as metabolic substrate
promotes storage of fat as triglycerides
how does insulin promote uptake and storage of glucose (4)
- insulin activates P13K
- P13K activates protein kinase B (PKB)
- PKB activates GLUT4
- GLUT4 allows entry of glucose into hepatocyte
how does insulin promote synthesis of new proteins (4)
- insulin binds to insulin receptor
- receptor activates P13K
- P13K activates TORC1
- TORC1 activates protein synthesis
Role of glucagon (2)
promotes gluconeogenesis to convert lipids and amino acids in glucose
promotes glucose release from glycogen stores (mainly liver)
what is glucagon produced by
alpha cells
glucagon dominates between meals (fasting state) and increases… (3)
glycogenolysis
gluconeogenesis
ketogenesis
insulin dominates after a meal (fed state) and increases… (4)
glycogen synthesis
protein synthesis
fat synthesis
glucose oxidation
how does insulin promote storage of fat as triglycerides
inactivates lipase which normally converts triglycerides to 3 fatty acids and glycerol
glucose is metabolised to glycerol and free fatty acids enter the adipocyte cell where they combine to form triglycerides
how does glucagon promote glucose release from glycogen stored
signal transduction pathway which is G-protein coupled
this activates cAMP/PKA-dependent signalling pathway
glucagon receptor = G-protein coupled receptor
what is glucagon release stimulated by (3)
hypoglycaemia
vigorous exercise
increased levels of amino acids
Glucagon role during starvation (hypoglycaemia)
- Glycogen stores used to increase glucose levels
- Glucagon stimulates formulation of glucose from lipids and amino acids (gluconeogenesis) by promoting lipid and protein degradation
symptoms of hyperglycaemia
weak tired itchy dry skin frequent urination increased thirst decreased appetite blurry vision fruity breath - ketones present
symptoms of hypoglycaemia
nervous irritability shaky dizzy hunger headache confused increased HR
what is type 1 diabetes
failure of insulin secretion from autoimmune destruction of beta cells
mediated by CD8 cytotoxic T-cells which recognise peptides from beta-cell specific protein and kills it
usually develops in early life
what is type 2 diabetes
insulin present in circulation but glucose conc remains high
usually develops later in life
obesity link in type 2 diabetes (6)
obesity leads to adipokines, free fatty acids and inflammation
= all 3 lead to insulin resistance in tissues
= beta cell compensation
= beta cell failure
= decreased insulin secretion
= type 2 diabetes
what is gestational diabetes
develops during pregnancy but tends to disappear after birth
beta cells cant produce enough insulin to meet the extra needs in pregnancy
possible consequences of gestational diabetes (5)
increased BP jaundice after birth increased risk of T2D development in future premature birth baby growing larger than normal
first line treatment for type 2 diabetes and general pharmacology (3)
metformin
activates AMPK (regulates lipid and glucose metabolism) increases lypolysis in liver and muscles = improves insulin receptor signalling suppresses glucose release from liver
first line treatment for type 1 diabetes and 3 types
insulin
animal (porcine/bovine), human analogue and human