Fig. 1.

Focal forebrain IR/IGF1R DKO eliminates signaling by receptor homodimers and hybrids in hippocampus or central amygdala. (A) Focal forebrain IR/IGF1R DKO eliminates homodimers and IR/IGF1R heterodimers and precludes distinct and collateral insulin, IGF-1, and IGF-2 signaling via these receptors. HR, IR/IGF1R hybrid receptors; IRS, insulin receptor substrate. (B) Targeted DKO in forebrain causes dramatic region-specific phenotypes. Hippo-DKO mice show anxiety, learning behavior deficits, and glucose intolerance, while CeA-DKO mice show defective thermogenesis via a previously unknown pathway linking this brain region to interscapular brown adipose tissue function. (C) Axial human brain magnetic resonance image showing bilateral hippocampi (red) and amygdalae (yellow).