normal endo pancreas 1 Flashcards
Islets of LangerhansSympathetic adrenergic input(______-nerve – from coeliac plexus)Parasympathetic, cholinergic input(___nerve)
- Splanchnic 2. Vagus
in ER, proinsulin is exposed to ______ excise C peptide, –> mature insulin. Insulin + C peptide packaged in Golgi into secretory granules : accumulate in the ___-.
- endopeptidases2.cytoplasm
What stimulates insulin secretion? (6)
• ↑ [ glucose ]• ↑ [ free aa ]• ↑ [ GI hormones ] (gastrin, secretin, CCK, GIP) • ↑ [ glucagon ]• Noradrenaline (low conc; α- receptors)• Acetylcholine
What inhibits insulin secretion? (4)
• Decreased [ glucose ]• ↑ [ somatostatin ] • Noradrenaline (high conc; β-adrenergic ) • Adrenaline (β-adrenergic )
What stimulates glucagon secretion? (3)inhibits? (1)
• Decreased [ glucose ]• ↑ [ free aa ]• Adrenaline• Increased [ glucose ]
What stimulates somatostatin? (4)
• Carbohydrates• Proteins• Fats• Decreased pH in duodenum
Insulin-Mediated Glucose Disposal (IMGD)• 85% of IMGD –> ______and _________
skeletal muscle + adipose tissue
GLUT4 (major t/p in muscle) Absence of insulin : •GLUT4 stored in ______ Insulin–> Fusion vesicles and insertion glucose transporters in ________
cytoplasmic vesiclesplasma membraneGLUT4:high affinity, insulin responsive
Effects of insulin on liver•Activates hexokinase –>____glucose (traps it in cell)•Activates glycogen synthesis enzymes e.g. _____and glycogen synthase•Inhibits activity of __________
phosphorylates phosphofructokinase glucose-6-phosphatase
Glycogen Synthase (GS)& Glycogen Phosphorylase (GP)PKA phosphorylates and activates PKB,which activates _____PKA phoshorylates and inactivates ___,:prevents cycling of glucose-1-P–>
Glycogen PhosphorylaseGlycogen Synthaseleads to Glycogen breakdown
Glucagon switches ___Glycogen Phosphorylase• Glucagon activates AC–> cAMP–>______ –> phosphorylase kinase—> GP GPb —> GPa
ON cAMP-dependent kinase (PKA)
Glucagon switches ____GS Glucagon activates PKA –> _____(hence inactivates) GS activates ____ Inhibits _____ Prevents dephosphorylation (hence reactivation) of ___________
OFF Phosphorylates glycogen phosphorylasephosphoprotein phosphataseglycogen synthetase
Insulin switches ON ____ ______ Insulin activates phosphoprotein phosphatase ________ glycogen synthetase Insulin inhibits cAMP-INdependent kinase Prevents____ (hence inactivation) of GS
glycogen synthetaseDephosphorylates phosphorylation
Insulin - ANABOLIC↑ net TAG synthesis:Activates __________Inactivates ___________
acteyl-CoA carboxylasehormone-sensitive lipase (HSL)
Glucagon – CATABOLICStimulates net breakdown of TAG (spares glucose)Inactivates________Activates_________
acteyl-CoA carboxylase hormone-sensitive lipase (HSL)
Glucose metabolism linked to Lipogenesis•Pyruvate enters TCA – citrate can exit for___•Glycolysis generates α-phospho-glycerate : backbone of __•Pentose phosphate pathway generates reduced ______
Fatty acid synthesisTAGcofactors for FA biosynthesis
Glucagon switches __acetyl-CoA carboxylase Glucagon activates PKA ___ a-CoA carboxylase also activates ___ Inhibits _____ ____ Prevents _____(hence reactivation) of a-CoA carboxylase
OFF Phosphorylates glycogen phosphorylasephosphoprotein phosphatasedephosphorylation
Insulin switches __acetyl-CoA carboxylase Insulin activates phosphoprotein phosphatase _______a-CoA carboxylase Insulin __cAMP-independent kinase Prevents _____ of acetyl-CoA carboxylase
ON Dephosphorylatesinhibitsphosphorylation
Hormone-sensitive lipase and futile cycling HSL catalyses rds in fat metabolism (TAG–> DAG +NEFA) ___stimulates FAS, so inhibits TAG metabolism to ___ Insulin ____HSL
Insulinprevent futile cycling inhibits
Hormone-sensitive lipase and futile cycling Glucagon stimulates fat catabolism to spare glucose / promote ____ Glucagon activates PKA ___HSL To spare glucose, ___increase fat metabolism by up-regulating expression of HSL.
gluconeogenesis Phosphorylates glucocorticoids
What % of pancreas is:exocrine (lobules)?ducts? endocrine (Islets of Langerhans) ?
- 80%2. 4%3. 2%