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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$