insulin signalling
TRANSCRIPT
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insulin signalling
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Neuro-anatomy of homeostatic regulation of food intake;opposing actions of AgRP/NPY and POMC/CAR containing
neurons
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!ncreased concentration of glucose in the "lood# after a meal#leads to increased AP production in the pancreatic "-cell and
this in turn reduces $% out&o'# leading to mem"ranedepolarisation( he su"se)uent C*% entry constitutes the
secretion signal
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Release of insulin in response to glucose leads toglucose uptake and storage in the form of glycogen
+in muscle and li,er
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the insulin receptor
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insulin receptor acti,ation and recruitment ofsignalling comple.
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Recruitment of adaptors and eectors through domainsthat "ind phosphotyrosine-containing peptides
01* domain+or P2 domain
phosphotyrosine peptidefrom !R03 +or insulin
receptor
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P! 4-kinase is an important eector for insulinsignalling
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Molecular structure of P! 4-kinase
ATP
P110
PI 3-kinase
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P! 4-kinaseproducts
+rele,ant to
insulin signallingis the production
of P!-4#5#6-P4
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A do'nstream eector of P! 4-kinase is the proteinkinase P$2
P7$* 8 phosphatidyl inositol-dependent protein kinase * 'as so named "ecause theidentity 'as unclear( !t is no' generally agreed that the mOR/Rictor comple. pro,ides
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the protein kinase 2 family
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7etail of the mechanism of acti,ation of proteinkinase 2
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P$2 phosphorylates 9O:O3 and this pre,ents if from going intothe nucleus
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oss of 9o.O3 in the nuclear leads to increased POMCand reduced AgRP e.pression
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P$2 stimulates the mOR path'ay# 'hich also pro,ides aanorectic signal +,ia an as yet unclear path'ay
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Rhe" is a <Pase 'hich# in its <P-"ound state#"inds 9$2P4=
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mOR is a huge atypical protein kinase of 'hich still a lot hasto "e learned
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A lack of glucose "locks the mOR-mediated anorectic signal( his occurs through an increase of 6>-AMP 'hich is produced in
a ? rescue path'ay 'here t'o A7P are com"ined to raisethe le,el of AP
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he glo"al picture of insulin# leptin# glucose andamino-acid Bmediated regulation of food intake ,ia
mOR and AMP$