FEEDING METABOLISM Flashcards
(33 cards)
Insulin blocks what metabolic processes?
Lipolysis and gluconeogeneis
How does glucose enter hepatocyte what processes are induced during feeding metabolism?
High blood glucose allows for transport down conc gradient into hepatocytes (GLUT2)
* glycogenesis, lipogenesis (de novo as well)
Discovery of insulin
Experiments in dogs
* purified from dog pancreas
* treat diabetic dogs from diff. fractions of pancreas
* purify further > use in humans
Blood supply in islets
Larger
* every single beta cell has capillary
* glucose from intestines flows here
* Insulin directed to capillaries > FAST travel
Insulin function
Inhibit liver activity and induce translocation of GLUT4 into muscle and adipose membrane
* glucose uptake
If production of liver glucose does NOT cease in presence of glucose…
sign of T2D
FOXO
Active in fasting state
* triggers transcription of G6P and PKA
What does Insulin do to FOXO
Insulin binds to hepatocytes > cascade
* activation of AKT
* phosphorlyate FOXO proteins
* bound to 14-3-3 molecules
What happens when FOXO is bound to 14-3-3 molecules?
Sequestered into cytoplasm
* out of nucleus > no transcription
More reproduction of AKT
Shutdown PKA signalling via PDE3B
* PDE3B bound to 14-3-3 > will now cleave cAMP and remove
* phosphorylate GSK3 > stimulate glycogen formation
de novo lipogenesis
Storing excess carbs
* glucose enter cell > glycolysis to pyruvate
* TCA cycle makes citrate > Acetyl-CoA
* FA made via FA synthesis
FA synthase
Go around and add 2 carbon units to FA chains until they’re ~16-18 carbons long
Receptor tyrosine kinase
Autophosphorylates tyrosine residues in cytoplasmic side of receptor
* become binding site
* IRS1 binds > become landing platform for PI3K
* specific lipid PIP3 generated (docking site for several kinases)
* eventually lead to activation of AKT
When PIP3 is present in plasma membrane…
PDK1 and AKT recruited to membrane
* double phosphorylation event on AKT > ACTIVATION
AKT phosphorylation can cause changes in…
- Glycogen synthesis
- Antilipolysis
- De novo lipogenesis (ACLY activity)
- Glucose uptake (decrease TBC1D4 activity, GLUT4 translocation)
enteroendocrine cells
In epithelial layer of SI
* sense nutrients in lumen
* release hormones
* go to BRAIN > impact food intake
* go to LIVER > regulate bile secretions
HPA Human Duodenum Enteroendocrine Markers
GCG - glucagon gene (specialised L cells produce GLP1)
* often make 2-3 hormones per cell
Gut hormones control…
Satiety
* on a time scale
* disapear quickly after digestion concluded
Hypothalamus
receives insulin signals directly
* also leptin
Ghrelin
secreted by the stomach
* stimulates food intake
GLP1
goes to hindbrain to inhibit food intake
If you take too much GLP1
excess stimulation of hindbrain -> nausea
Semaglutide
GLP1 mimetic that lasts longer
* AA sub. @ 2nd pos > stops cleavage in blood
* mutation @ 26th pos > contains FA tail, sticks to albumin and stops kidney elimination
* AA sub. @ 34 pos > prevents incorrect FA binding
