Insulin receptor substrate IRS

Leptin makes the cells of liver and muscle more sensitive to insulin. One hypothesis to explain this effect suggests cross-talk between the protein tyrosine kinases activated by leptin and those activated by insulin (Fig. 23-35) common second messengers in the two signaling pathways allow leptin to trigger some of the same downstream events that are triggered by insulin, through insulin receptor substrate-2 (IRS-2) and phos-phoinositide 3-kinase (PI-3K) (Chapter 12). 

FIGURE 23-35 A possible mechanism for cross-talk between receptors for insulin and leptin. The insulin receptor has intrinsic Tyr kinase activity (see Fig. 12-6), and the leptin receptor, when occupied by its ligand, is phosphorylated by a soluble Tyr kinase (JAK). One possible explanation for the observed interaction between leptin and insulin is that both may phosphorylate the same substrate—in the case shown here, insulin receptor substrate-2 (IRS-2). When phosphorylated, IRS-2 activates PI-3K, which has downstream consequences that include inhibition of food intake. IRS-2 serves here as an integrator of the input from two receptors. 

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