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25 Cards in this Set
- Front
- Back
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Broadly, how is glucose homeostasis maintained? |
By the balance of hormones
Anabolic - insulin, hypoglycemia, Catabolic - glucagon, cortisol, hyperglycemia, |
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What cell types are found in the Islet of Langerhans? What do they secrete? Which is the largest cell type? |
Alpha (largest) - glucagon, outer edges
Beta - insulin, central region Delta - somatostatin Gamma - pancreatic polypeptide |
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What is of interest in the structure of beta cells? |
Extensive ER and Golgi
Many dense core m-bound secretory granules with insulin |
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Briefly, how is insulin synthesised? |
As a larger precursor - preproinsulin
Becomes proinsulin when sp removed in ER C peptide cleaved in secretory granules to form insulin |
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How is insulin released? |
Fusion of the dense core granule membrane with the plasma membrane of the b cell
Requires ATP and Ca2+ |
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What is the stimulus for insulin release? |
Main - glucose conc.
aa Glucagon GI hormones secreted after food ingestion (GIP, CCK, VIP) PS stimulation increases (ACh), S (adrenalin) inhiibts insulin release |
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How does glucose enter B cells |
GLUT-2
An increase in blood [Glucose], leads to an increase in cytosolic [Glucose]Glucose is phosphorylated by glucokinaseStimulates glucose metabolism and ATP/ADP ratio increases Closes ATP sensitive K+ channel in plasma membrane Depolarises cellOpens voltage dependent Ca2+ channel Ca2+ influx elevates cytosolic [Ca2+] which triggers granule exocytosis
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What is the glucose sensor? |
GLUT 2 and glucokinase (5 mM/L)- work together
GLUT - low glucose affinity (20mM), high activity Transports glucose into cell when high glucose |
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What is the mode of insulin? |
Insulin, c-peptide and proinsulin in plasma
Degraded in liver, kidney Binds insulin receptors, internalised and degraded in target tissues |
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What are the triggers for glucagon secretion? |
Low blood glucose
Presence of glucogenic aa (alanine) GI homrones (CCK, VIP) Action of B-adrenergic/cholinergic stimulation |
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What depresses glucagon secretion? |
High blood glucose High free fatty acid in blood High insulin Somatostatin |
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What is the mode of glucagon? |
Plasma - pancreatic glucagon, glycentin, glucagon-like peptides
Degraded by plasma and liver/kidney, 5 min HL Bind receptors, internalised and degraded |
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What is the effect of insulin on target cells? |
Results in receptor dimerisation and aggregation and autophosphorylation and phosphorylation of effector proteins Increases: GTPase, phosphodiesterase, tyrosine kinase Represses gluconeogenic and catabolic enzymes and induction and biosynthesis of anabolic enzymes |
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What is the effect of insulin? |
Promotes anabolism
- increases carb/lipid storage - increases protein synthesis - suppresses catabolism Liver, adipose, muscle |
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What is the effect of glucagon on metabolism? |
Antagonistic
Catabolism of liver glycogen and adipose triglyceride Stimulates hepatic gluconeogenesis Inhibits protein/lipid synth. |
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Why does glucagon not directly affect muscle? |
No receptor present
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Effect of insulin on liver? |
Stimulates glycolysis, glycogen synthesis
Suppresses lipolysis and gluconeogenesis Stimulates FA, tri. synth. - synth. of VLDL |
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Effect of insulin on adipose tissue? |
Trigly. synth. from glycerol-3-phosphate and FA Glucose transport, upregulation of GLUT4 |
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Effect of insulin on muscle? |
Glucose transport, upregulation of GLUT4 Increases glucose metabolism and glycogen synthesis Increases uptake of aa and protein synth. |
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What is the effect of glucagon on liver? |
Stimulates gluconeogenesis (intakes glucogenic aa, production of enzymes)
Decreases glycolysis (lowers PFK-1 activity) Inhibits glycogenesis, stimulates glycogen degradation Inhibits lipogenesis- inhibits acetyl CoA carboxylase Stimulates ketogenesis - influx of fatty acids - B-oxidation producing acetyl-CoA |
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What is the effect of glucagon on adipose tissue? |
Lipolysis by cAMP mediated activated of lipase
FFA exported, oxidised to yield energy Export glycerol for gluconeogenesis in liver |
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How is PFK-2 regulated? |
Bifunctional enzym, 2 separate active sites Phosphorylation by cAMP-dependent protein kinase inhibits synthesis and stimulates degradation of PFK-2 So [F-2,6-BP] decreases, no PFK stim, no glycolysis |
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How is PFK regulated? |
- PKA phosphorylation
- Allosterically by F1,6-BP, ATP and alanine |
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What is the effect of adrenaline? |
Similar to glucagon
Inhihits glycolysis and lipogenesis Stimulates gluconeogenesis |
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What is the effect of calcium on phosphorylase kinase? |
Ca binds calmodulin (delta subunit of enzyme in muscle)
Phosphorylation, via cAMP cascade, results in further activation |
