USMLE (Fach) / Endocrine (Lektion)

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Synthesis: Preproinsulin (synthesized in RER) → cleavage of "presignal" → proinsulin (stored in secretory granules) → cleavage of proinsulin → exocytosis of insulin and C-peptide equally.

Function: Binds insulin receptors (tyrosine kinase activity), inducing glucose uptake (carrier-mediated transport) into insulin-dependent tissue and gene transcription. - Tyrosine phosphorylation → Phosphoinositide-3 kinase pathway → GLUT4 expression, glycogen, lipid, protein synthesis- Tyrosine phosphorylation → RAS/MAP kinase pathway → cell growth, DNA synthesis

Anabolic effects of insulin: ↑ glucose transport in skeletal muscle and adipose tissue↑ glycogen, triglyceride, protein synthesis↑ Na+ retention (kidneys)↑ cellular uptake of K+ and amino acids↓ glucagon release- Unlike glucose, insulin does not cross placenta.

Insulin-dependent glucose transporters:- GLUT-4: adipose tissue, striated muscle (exercise can also ↑ GLUT-4 expression)Insulin-independent transporters:- GLUT-1: RBCs, brain, cornea, placenta- GLUT-2 (bidirectional): β islet cells, liver, kidney, small intestine- GLUT-3: brain, placenta- GLUT-5 (fructose): spermatocytes, GI tract- SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine

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