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. Author manuscript; available in PMC: 2022 Feb 1.
Published in final edited form as: Trends Endocrinol Metab. 2020 Dec 23;32(2):118–129. doi: 10.1016/j.tem.2020.11.008

Table 1.

Canonical and Non-Canonical Metabolic Functions of β-Arrestins Revealed by the Use of Cell-Type Specific Mutant Mouse Models

Cell type Mutant mouse strain Key metabolic phenotypes Likely molecular mechanism(s) References
Phenotypes due to canonical β-arrestin functions
Adipocytes Adipo-βarr2-KO Decrease in adiposity (HFD mice) Improved glucose homeostasis Relative lack of metabolic deficits in response to HFD feeding Lack of βarr2-mdeiated inhibition of β3-adrenergic receptor signaling [34]
Hepatocytes Hep-βarr2-KO Impaired glucose homeostasis Lack of βarr2-mediated inhibition of glucagon receptor signaling [49]
Hep-βarr2-OE Relative lack of metabolic impairments due to HFD feeding Enhanced βarr2-mediated inhibition of glucagon receptor signaling [49]
Phenotypes due to non-canonical β-arrestin functions
Adipocytes Adipo-βarr1-KO Impaired glucose tolerance and insulin sensitivity (HFD mice) Increases myostatin expression in BAT due to the lack of nuclear βarr1activity [51]
Adipo-βarr1-OE Improved glucose tolerance and insulin sensitivity (HFD mice) Reduced myostatin expression in BAT due to enhanced nuclear βarr1 activity [51]
β-Cells Beta-βarr2-KO Impaired insulin release and glucose tolerance (HFD mice) Impaired CAMKII function due to βarr2 deficiency [21]
Beta-βarr2-OE Increased insulin secretion and improved glucose tolerance (HFD mice) Enhanced CAMKII activity (likely mechanism) [21]
Beta-βarr1-KO Reduced efficacy of SU drugs to promote insulin secretion Impaired Epac2 function due to βarr1 deficiency [22]
Skeletal muscle cells SKM-βarr2-KO Slight improvements in glucose and insulin tolerance (HFD mice) Enhanced insulin-induced Akt activation in SKM due to βarr2 deficiency [76]
AgRP neurons AgRP-βarr1-KO Impaired glucose tolerance and insulin sensitivity (HFD mice) Lack of βarr1 prevents insulin from silencing AgRP neurons [83]
AgRP-βarr1-OE Improved glucose homeostasis and insulin tolerance Enhanced insulin sensitivity of AgRP neurons [83]

Abbreviations: SU, sulfonylurea; HFD, high-fat diet; SKM, skeletal muscle; KO, knockout; OE, overexpression.