Regulation of glucose Flashcards
Semester 1 year 1
Where are the Islets of Langerhans found?
In endocrine tissue
What are the main secretory Islet of Langerhans cells?
-beta (65%)
-alpha (20%)
-delta (10%)
What other single/grouped endocrine cells are there?
-F (PP/gamma) cells
-ε cells
-enterochromaffin cells
What do beta, alpha, delta, F and ε cells secrete?
-beta = insulin, proinsulin, C peptide, amylin
-alpha = glucagon
-delta = somatostatin
-F = pancreatic polypeptide
-ε = Ghrelin protein
How does humoral communication and control occur in the Islets of Langerhans?
Small arteries enter the Islet core + distribute blood via fenestrated capillaries
How does cell to cell communication occur in the Islets of Langerhans?
-gap junctions between beta and alpha cells
-delta cells send dendrite-like processes to beta cells
What neurons are the islets innervated by?
-adrenergic
-cholinergic
-peptidergic
What is the primary pathway for secretion in beta cells?
-glucose enters cell via GLUT2, is phosphorylated + oxidised to form G6P
-ATP inhibits K+ dependent channel, so membrane depolarises
-causes Ca2+ gated channel to open + Ca2+ to enter down electrochemical grad.
-influx of Ca2+ causes vesicles containing insulin to move + fuse with membrane
-insulin released by exocytosis
What is the secondary pathway for secretion in beta cells?
-acts via G protein coupled receptors
-CCK + acetylcholine move in via G protein coupled receptor
-converted to PKC
-causes fusion of vesicle with membrane + insulin release via exocytosis
What is the third pathway for secretion in beta cells and what inhibits and upregulates it?
-ATP converted to cAMP via adenylyl cyclase
-cAMP converted to PKA
-causes fusion of vesicle with membrane + insulin release via exocytosis
-inhibited by somatostatin + alpha adrenergic agonists
-upregulated by beta adrenergic agonists + glucagon
What regulates insulin secretion?
Islet beta cell receptors
How does high and low blood glucose effect insulin secretion?
-high = stimulates insulin synthesis + secretion
-low = inhibits secretion
What does sympathetic stimulation cause in relation to insulin secretion?
-beta adrenergic stimulation increases secretion
-alpha adrenergic stimulation decreases secretion
What effect does parasympathetic stimulation have on insulin secertion?
Increase secretion
What effect do drugs acting on K+ ATP channels have on insulin secretion?
Increase secretion
What humoral factors can regulate insulin secretion?
GIP (K cells of SI), amylin (beta cells), somatostatin
What is a heterotameter?
Made up of alpha/beta subunits + intracellular tyrosine kinase
What does receptor activation result in?
Initiates a cascade of phosphorylation events to activate or inhibit: PKC, phosphatases, phospholipases, G proteins
Which cells are particularly targeted by insulin?
All body cells targeted, but specifically liver + muscle cells
What is glycogenesis?
Conversion of glucose to glycogen for storage
What is lipogenesis?
Conversion of glucose to fat in fat cells when glycogen stores replenish
What is gluconeogensis?
Production of glucose from non-sugar precursors e.g amino acids
What is glycogenolysis?
Hydrolysis of glycogen to glucose
How does insulin act in liver cells?
-promotes formation of glycogen from glucose (glycogenesis)
-inhibits glycogenolysis + gluconeogenesis
How does insulin act in muscle cells?
-promotes glucose uptake by increasing no. of GLUT4 transporters in membrane
-promotes glycogenesis
-promotes glycolysis + carb oxidation, preventing gluconeogenesis
-promotes protein synthesis + inhibits protein hydrolysis to decrease blood amino acid conc. + increase uptake
How does insulin act in adipocytes?
-increased GLUT4 transporter expression for rapid glucose uptake
-glucose converted to fatty acids + stored as triglycerides
-increased lipoprotein lipase to liberate fatty acids for triglyceride synthesis
-inhibits mobilisation + oxidation of fat stores to decrease circulating fatty + keto acids
What is diabetes mellitus and what are the different types?
-high blood sugar over prolonged periods
-type 1 = pancreatic Islet destruction due to autoimmune response
-type 2 - low insulin production (+ peripheral insulin resistance)
What are the symptoms of type 1 diabetes mellitus?
-hyperglycaemia - decreased uptake into cells
-increased blood FA + keto acid conc.
-increased blood amino acid conc.
-osmotic diuresis - unable to reabsorb water into blood, so large urine vol
-polyuria
-hypotension
-hyperkalaemia - K+ moves out of cells
What is the treatment for type 1 diabetes mellitus?
Insulin replacement therapy
What are the symptoms of type 2 diabetes mellitus?
-increased thirst + hunger
-frequent urination
-weight loss
-fatigue + blurred vision
-headaches
What are they treatments for type 2 diabetes mellitus?
-sulphonyurea drugs - stimulate insulin secretion
-biguanide drugs - upregulate receptors on target tissues
-calorie restriction/weight loss
