Table 1.

Summary of the studies highlighting a link between BVR-A alterations and insulin signaling-related pathways in metabolic diseases.

Model	BVR-A Alteration(s)	Insulin Signaling Alteration(s)	Observed Effect(s)	Ref.
Ob/Ob mice	Stimulation of BVR-A kinase activity by KYCCSRK peptide	Increase of IR activation	Rapid glucose clearance from the circulation	[55]
Liver-specific BVRA KO mice	Liver deletion of BVR-A	Reduced GSK3β inhibition	Impaired glucose tolerance and development of fatty liver	[56]
HFD-treated BVRA KO mice	Adipocyte deletion of BVR-A	Decreased Akt activation and reduced GLUT4 levels	High fasting blood glucose levels; adipocytes hypertrophy and reduction of mitochondrial number in white adipose tissue	[57]
BVRA KO mice	Global BVRA deficiency	-	Fatty liver without alteration in glucose metabolism and insulin sensitivity	[58]
Obese subjects	Reduced BVR-A levels in PBMC	Aberrant activation of insulin signalling characterized by: reduced IRSSer307/IRS1 ratio; increased pAktSer473/Akt and increased pGSK3βSer9/GSK3β ratio; increased AS160-mediated GLUT4 translocation	Metabolic syndrome, presence and severity of NAFLD and adipose tissue dysfunction	[59]
Obese subjects	Reduced BVR-A expression in visceral adipose tissue	-	Larger adipocytes size and greater local expression of inflammatory and hypoxia markers	[60]
T2D subjects	Reduced BVR-A levels in PBMC	-	Glyco-metabolic impairment and increased inflammatory condition	[61]

Abbreviations: BVR-A: Biliverdin Reductase A; Ob: obese; IR: Insulin Receptor; KO: Knock-out; GSK3β: glycogen synthase kinase 3 beta; HFD: high fat diet; GLUT4: glucose transporter type 4; PBMC: peripheral blood mononuclear cell; IRS: insulin receptor substrate; NAFLD: non-alcoholic fatty liver disease; T2D: type 2 diabetes.