regulation of blood glucose levels by pancreatic hormones Flashcards
what is the absorptive state?
- ingested nutrients enter blood stream from GI tract
- these nutrients support energy requirements of the body
- excess nutrients are stored
what is the post-absorptive state?
- no nutrients are entering bloodstream from GI tract
- switch to net catabolism of stores- break down of glycogen, fat and protein
- the post absorptive state must maintain blood glucose levels in absense of absorption from the GI tract (brain normally only uses glucose for energy)
what are the main tissues which store glucose for future use?
liver, skeletal muscle and adipose tissue
what is the main supplier of blood glucose in the post absorptive state?
liver
produces glucose via gluconeogenesis and glycogen breakdown
what cells secrete insulin and glucagon?
pancreatic islets
what cells produce glucagon?
alpha
what cells produce insulin
beta
what type of hormones are glucagon and insulin?
peptide
what happens in the liver when insulin is released in the absorptive state?
- increased glucose uptake
- increased glycolysis
- increased glycogen synthesis
- inhibition of gluconeogenesis
- inhibition of glycogen breakdown
what happens in the skeletal muscle when insulin is released in the absorptive state?
- increased glucose uptake
- increased glycolysis
- increased glycogen synthesis
- inhibition of glycogen breakdown
what happens in adipose tissue when insulin is released in the absorptive state?
- increase glucose uptake
-increased glycolysis - increased triglyceride synthesis
what cells does drugs for type 2 diabetes work on?
beta cells
how does glucose regulate insulin release from beta cells?
- increased uptake and metabolism leads to an increase in ATP:ADP ratio
- increased ratio leads to closure of ATP sensitive K+ channels and membranes depolarise
- depolarisation of membrane leads to opening of voltage gated Ca2+ channels
- results in increased cytosolic promotes secretion of insulin via exocytosis of insulin granules
how does activation of protein kinase B occur?
- Binding of insulin to the insulin receptor leads to receptor auto-phosphorylation
- phosphorylation residues on the IR act as binding sites for insulin receptor substrate proteins
- IR phosphorylates IRS proteins
- phosphoinositide 3-kinase, binds to phosphorylated residue on IRS and converts lipid PIP2 into PIP3
- Binding to PIP3 activated PDK1, which then phosphorylates and activates protein kinase B
- activated PKB mediated many intracellular effects of insulin
how does insulin stimulate glucose uptake into skeletal muscle and adipocytes?
increased the amount of glucose transported called GLUT4 at the cell surface
what does activation of PKB activate?
exocytosis which releases GLUT4
what is the activation of glycogen synthase regulated by?
phosphorylation
what happens when an enzyme is phosphorylated?
it inactivates it
what breaks down glycogen synthase to the inactive form?
glycogen synthase kinase
how does increased glycogen synthesis occur?
- insulin signalling leads to activation of PKB
- PKB phosphorylates and inactivates GSK
- this leads to increase of the active form of glycogen synthase
- increased activity of glycogen synthase increases glycogen synthesis
what is gluconeogenesis regulated by?
transcription factor Fox01
where is Fox01 synthesised?
in the cytosol but moves to the nucleus to perform function
how does insulin inhibit gluconeogenesis in the liver?
PKB phosphorylates Fox01 which prevents it from entering the nucleus
This turns off expression of gluconeogenic genes
how does type 1 diabetes arise?
due to loss of insulin synthesis/ release from pancreatic beta cells
