Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
Kadowaki
Takashi
T
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. kadowaki-3im@h.u-tokyo.ac.jp
Yamauchi
Toshimasa
T
Kubota
Naoto
N
Hara
Kazuo
K
Ueki
Kohjiro
K
Tobe
Kazuyuki
K
D052242:Adiponectin / Q000097:blood* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C475418:ADIPOR1 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface