The Endocrine Pancreas Flashcards
What does SGLT1 do?
Glucose absorption from gut
What transporters are responsible for glucose reabsorption from the kidney?
SGLT1 and 2
Where are GLUT4 receptors found?
Muscle and adipose tissue
Which of the GLUT transporters are insulin dependant?
GLUT4
What does the affinity of a transporter relate to?
Rate at which glucose moves down the concentration gradient
What does a high/low transporter affinity mean?
Constant movement (high), changeable movement (low)
What are the islets of langerhans?
Clusters of endocrine cells surrounded by the exocrine pancreas
What do the alpha, beta and delta cells in the islets of langerhans secrete?
Alpha = glucagon Beta = insulin Delta = somatostatin
Why is C peptide useful?
Metabolically inert so a good marker for if there’s insulin or not
What vessels supply the pancreas?
Branches of the coeliac, superior mesenteric and splenic arteries
Where do the pancreatic veins drain into?
Portal system
What stimulates insulin secretion?
Plasma glucose, amino acids, glucagon, incretin hormones and PNS
What inhibits insulin secretion?
Somatostatin and alpha adrenergic
What inhibits glucagon secretion?
Plasma glucose and somatostatin
What stimulates glucagon secretion?
Amino acids, beta adrenergic and PNS
How can ACh cause an increase in intracellular [calcium]?
Phospholipase C pathway -> increase in insulin secretion
How can adenylate cyclase increase insulin secretion?
cAMP -> PKA which increase the effect of calcium on the granule exocytosis
What inhibits adenylate cyclase?
Adrenaline
What type of receptors are glucagon and insulin?
Glucagon = GPCR Insulin = tyrosine kinase
What happens when insulin binds to its receptor?
- Translocation of GLUT4 transporter to plasma membrane -> influx of glucose
- glycogen synthesis
- glycolysis
- fatty acid synthesis
- metabolic enzyme activity modulation (gene transcription regulation)
What is the insulin receptor made up of?
Tetrameric- 2 alpha subunits on surface and 2 beta which span the membrane and are bound to IRS proteins
What does IRS stand for?
Insulin receptor substrate
What is acetyl CoA carboxylase inhibited by?
PKA
What are most glucagon actions mediated by?
Adenylate cyclase or production of cAMP -> pKa
What are the [plasma glucose] cutoffs for diabetes?
Random plasma glucose >11.1mmol/L
Fasting plasma glucose >7mmol/L
Oral glucose tolerance test > 11.1 mmol/L
How do you carry out the oral glucose tolerance test?
Give a person 75g glucose and measure blood every half an hour for 2 hours
What is glycemic control?
Balancing hypoglycaemia with hyperglycaemia
What are a good indication of glycemic control?
Glycosylated Hb control
What microvascular complications are common in badly controlled diabetes mellitus?
Damage in capillary beds/ nerves (retinopathy or loss of feeling in legs)
Why is glycaemic control hard in diabetes patients?
- insulin is highest in pancreas and liver in normal people, but when you inject it its diluted by the time it gets to pancreas and liver
- other modulating factors are lost by injecting insulin
What is the incretin effect?
Increase insulin secretion in a person when glucose was administered orally vs IV
Why is the incretin effect a thing?
When glucose is absorbed in the GIT incretin hormones are released
What does incretin act to do?
Boost insulin secretion
What are the two incretin hormones?
Glucagon-like peptide-1 (GLP-1) and GIP
What are the names of drugs used in the treatment of Type 1 diabetes mellitus?
Metformin, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, incretin target drugs
What does metformin do?
Decreases gluconeogenesis
What do sulfonylureas do?
Bind and close KATP channels, depolarise B cells, which releases insulin
What do thiazolidinediones do?
Activate PPARgamma receptors which reduce insulin resistance (dont know how)
How do SGLT2 inhibitors work?
Promote glucose excretion via kidney
How do incretin targeting drugs work?
Potentiate insulin release in response to resting plasma glucose
