1. insulin signalling

2. Neuro-anatomy of homeostatic regulation of food intake; opposing actions of AgRP/NPY and POMC/CART containing neurons

4. Increased concentration of glucose in the blood, after a meal, leads to increased ATP production in the pancreatic b-cell and this in turn reduces K+ outflow, leading to membrane depolarisation. The subsequent C2+ entry constitutes the secretion signal

5. Release of insulin in response to glucose leads to glucose uptake and storage in the form of glycogen (in muscle and liver)

6. the insulin receptor

7. insulin receptor activation and recruitment of signalling complex

8. Recruitment of adaptors and effectors through domains that bind phosphotyrosine-containing peptides SH2 domain (or PTB domain) phosphotyrosine peptide from IRS1 (or insulin receptor)

9. PI 3-kinase is an important effector for insulin signalling

10. Molecular structure of PI 3-kinase ATP P110 PI 3-kinase

11. PI 3-kinase products (relevant to insulin signalling is the production of PI- 3,4,5-P3

12. A downstream effector of PI 3-kinase is the protein kinase PKB PDK2 : phosphatidyl inositol-dependent protein kinase 2 was so named because the identity was unclear. It is now generally agreed that the mTOR/Rictor complex provides the initial phosphorylation

13. the protein kinase B family

14. Detail of the mechanism of activation of protein kinase B

15. PKB phosphorylates FOXO1 and this prevents if from going into the nucleus

16. Loss of FoxO1 in the nuclear leads to increased POMC and reduced AgRP expression

17. PKB stimulates the mTOR pathway, which also provides a anorectic signal (via an as yet unclear pathway)

18. Rheb is a GTPase which, in its GTP-bound state, binds FKBP38

19. mTOR is a huge atypical protein kinase of which still a lot has to be learned

20. A lack of glucose blocks the mTOR-mediated anorectic signal. This occurs through an increase of 5’-AMP which is produced in a « rescue » pathway where two ADP are combined to raise the level of ATP

21. The global picture of insulin, leptin, glucose and amino-acid – mediated regulation of food intake via mTOR and AMPK

22. from PKB to glycogen synthase