Acute regulation of glucose Flashcards
Within what range must plasma [glucose] remain?
3-10 mM
Which of the glucose transporters (SGLT or GLUT) require Na+?
SGLT
Which of the GLUT transporters is insulin responsive?
GLUT-4
What are the most abundant cells in the islets of Langerhans, what do they secrete and where are they located?
Beta cells - centrally located. Insulin.
Where are alpha cells found and what do they secrete?
At the periphery - secreting glucagon.
What do delta cells secrete?
Somatostatin
What do F cells secrete?
Pancreatic polypeptide.
How do beta cells sense glucose (and AA)?
By using it to make ATP.
Which transporter does glucose use to enter beta cells?
GLUT-2 - insulin insensitive and low affinity
What is the effect of a rising [ATP] within the beta cell?
Closes K+ATP channel depolarising the membrane. Ca2+ influx and CICR induce exocytosis of insulin.
Do you get a larger insulin response to oral or IV glucose?
Oral
What sort of insulin response is elicited by IV glucose?
Biphasic
What other pathways may increase insulin exocytosis?
Other secretagogues (incretins) act via cAMP or PLC pathways.
Which G protein pathway antagonises the pathway?
Gi
What is the effect of the parasympathetic nervous system on secretion?
Increases
What is the effect of the sympathetic nervous system on insulin secretion?
Inhibits.
How is insulin produced?
Prohormone
How is insulin processed in the Golgi?
Cleaved to give A and B chains which are linked by disulphide bridges. Inactive C-peptide also produced.
How is C-peptide useful?
As a marker of endogenous insulin production.
What kind of receptor is the insulin receptor?
Tyrosine kinase - TK domains phosphorylate each other and nearby proteins - insulin receptor substrates.
What are the two main pathways of insulin receptor signalling?
PI3K and PKB phophorylate proteins altering activity and inserting (GLUT 4)
MAPK pathway alters gene expression.
What are the effects of insulin on the liver?
Glycogen storage and VLDL production increase while gluconeogenesis and ketone body production are inhibited. No GLUT-4 involved.
What are the effects of insulin on the muscles?
GLUT-4 inserted and favours the use of glucose. Glycogen, triglyceride and protein synthesis increase.
Exercise via adrenaline also induces GLUT-4 and synergises with insulin.
LPL exported to endothelium where it extracts free fatty acids (FFA) from VLDL.
What are the effects of insulin on fat?
GLUT-4 inserted and favours uptake of glucose. Trigylceride storage increased. Export of FFA and glycerol reduced.
What drives the release of glucagon from alpha cells?
Amino acids.
What antagonises the release of glucagon from alpha cells?
Glucose
What happens to glucagon in L cells?
Converted to GLP1 - potent incretin.
What are the effects of glucagon on the liver?
Glucagon receptor linked to Gs. Glycogen breakdown and gluconeogenesis increase. Presence of G6Pase allows glucose export. Fatty acids used as an energy source and for ketone body production.
What are the effects of glucagon on fat and muscle?
At high levels causes: lipolysis in adipocytes, proteolysis (releasing AA for gluconeogenesis) in muscle.
What organ clears glucagon?
Liver
Aside from the pancreas, from where else is somatostatin released?
D cells of stomach, duodenum and pancreas. Release stimulated by lumenal H+ and inhibited by ACh.
What is the function of somatostatin?
Acts on G cells to inhibit the release of gastrin. Also inhibits the release of CCK and secretin (and insulin/glucagon if it can get to the cells).
What is the effect of exercise on glucose homeostasis?
Adrenaline signals via cAMP to enhance:
- Glucose production in the liver (inc. Cori cycle)
- Glycogen breakdown in muscle and GLUT4 insertion
- Fatty acid release from adipocytes
What is the impact of excess glucagon in the type 1 diabetes?
Leads to lipolysis an proteolysis.
Gluconeogenesis and ketogenesis in the liver.
What are plasma insulin levels in type 2 diabetes?
Often high
