L19 Acute Regulation of Glucose Flashcards
What is the role of GLUT-2?
A passive glucose transporter found on the kidney, ileum, liver, and pancreatic beta cells. It is low affinity.
Which passive transporter of glucose is insulin responsive?
GLUT-4 - found on skeletal muscle, heart and adipocytes
Give examples of 2 sodium symport transporters?
SGLT-1 (high affinity and found on the apical brush border of the small intestine and kidney tubules) and SGLT-2 (low affinity found on kidney proximal tubule).
Which glucose transporter is constitutive?
GLUT-1 (Brain, RBC and beta cells)
Which GLUT transporter is used to transport fructose?
GLUT-5
How are the Islets of Langerhan’s arranged?
The arterioles run into the centre of the islets and the capillaries pass out towards the periphery. Beta cells express insulin. Most of the cells are beta cells. Alpha cells are scattered around the outside, not so many of them, and secrete glucagon.
There are a few delta cells producing somatostatin and a few F cells which produce pancreatic polypeptide. Blood flows out and picks up glucagon as it comes out.
How is insulin secreted from beta cells?
- Beta cells have ATP gated potassium channel in the cell membrane. When there is lots ATP present it is not open, potassium doesn’t flow out and the cell doesn’t become hyperpolarised. When lots of ATP around the cell becomes depolarises and then it secretes insulin.
- These cells have GLUT2 transporters and so are sensitive to glucose levels, as the glucose levels rise, they transport more glucose in. They also have amino acid transporters and so are sensitive to amino acid levels. After a meal, there is lots of glucose and amino acids, leading to the production of ATP. The potassium channels are shut, the cells are depolarised and voltage gated calcium channels are triggered and calcium influx is triggered causing the exocytosis of insulin.
What is the difference in response to IV glucose compared to oral glucose?
Eating glucose has a much bigger effect on insulin production than giving IV.
What is an incretin?
A hormone that stimulates a decrease in blood glucose levels.
What is the structure of the insulin receptor?
The insulin receptor dimerises, using disulphide bridges. They are tyrosine kinase receptors. The C terminus is a tyrosine kinase, and will phosphorylate other molecules.
What is the effect of activation of the insulin receptor?
Insulin comes in and binds to the receptor activating the kinase enzyme which can then phosphorylate a number of things. The cells express specific proteins, insulin receptor substrates, who wait around to the phosphorylated by the insulin receptor. Once phosphorylated, they can then go onto do other things. They act as signalling molecules.
After these substrates are phosphorylated there are two pathways:
- Fast pathway - works through PI3K and PKB phosphorylate proteins alerting activity and inserting GLUT4 to the membrane. Controls metabolism.
- Slow pathway: Uses MAPK and alters gene expression, will tend to have longer term responses such as growth and anabolic responses.
Both mediated but Insulin receptor substrates.
What is the effect of insulin on the liver?
Liver: On the membrane of hepatocytes there is GLUT2 and so it always permeable to glucose. It doesn’t have GLUT4 and so all the responses are in terms of metabolic changes. Pathways which favour storages of glycogen are switched on: phosphorylation of glucose to G6P and conversion for G1P to glycogen. Reduce the activity of enzymes going the other way. Favour the movement of glucose down the glycolysis pathway and into the mitochondria for acetyl CoA - this is used for fats. The liver packages this as VLDL, which are used elsewhere. Longer term anabolic pathways are favoured.
What is the effect of insulin on muscle?
Muscles: In the muscle insulin receptors. Have GLUT4, insulin receptors trigger the insertion of GLUT4 into the membrane. The muscle uses glucose as a food substrate and uses it in the TCA cycle for ATP and favour fats storage rather then fatty acids as a food storage. Longer term anabolic process makes new muscle proteins.
What is the effect of insulin on fat?
Fats: Insulin receptor puts GLUT4 in the membrane favouring glucose uptake. It then favours pathways which lead to the production of fatty acids. VLDL made in the liver, are taken up by adipocytes as they increase expression of lipoprotein lipase. This helps to buffer glucose load.
What is GLP1?
Glucagon-like peptide.
Glucagon is released by alpha cells and driven by amino acids and antagonised by glucose. L cells in the small intestine make the same initial product but cleave it in a different way to make different products such as glucagon like peptide a potent incretin, like glucagon.
