Table 1.

A summary of studies using Cre/loxP system to probe physiological roles of InsR signaling in different brain cell types

Name	Cell-type of interests	Cre-driver	Main findings of the InsR KO phenotypes	Physiological importance	Refs
NIRKO	brain-specific	Nestin-Cre	increased food intake in females; mild insulin resistance and dyslipidemia; hypothalamic hypogonadism; loss of insulin stimulated PIP3 signaling Tau hyperphosphorylation; attenuated phosphorylated hepatic STAT3; impaired GLUT4 translocation; brain mitochondrial dysfunction; dopaminergic dysfunction; late-age onset-related anxiety- and depression-like behaviors	Regulation of energy disposal, fuel metabolism, reproduction, brain-liver crosstalk, glucose sensing, brain cholesterol metabolism, mitochondrial function, and dopamine signaling	[5, 6, 42–44, 107, 142]
GIRKO	Astrocyte-specific	GFAP-Cre, GFAP-CreERT2, GLAST-CreERT2	impaired responses to changes in glucose availability; decreased ATP release from astrocytes; anxiety- and depression-like behaviors; longer and irregular estrus cycles; decreased pregnancy rates and reduced litter sizes; dysregulation of the HPG axis	hypothalamic glucose sensing, regulation of systemic glucose metabolism, dopaminergic signaling, ATP exocytosis, HPG axis	[7, 62, 143]
EndoIRKO	Vascular endothelial cells-specific	Cdh5-Cre Slcolc1-CreERT2	delayed onset of insulin signaling in the brain; decreased levels of hypothalamic POMC, increased food intake and obesity; delayed acute hypoglycemic effect of systemic insulin administration and impaired glucose tolerance; Not necessary to maintain insulin sensitivity	Transendothelial insulin delivery; kinetics of insulin signaling	[74, 77, 79]