Adiponectin is a recently identified adipose tissue-derived
protein (
adipocytokine) with important metabolic effects. It is exclusively expressed in adipose tissue and released into the circulation.
Adiponectin expression and/or secretion is increased by
insulin like growth factor-1 and
ionomycin, and decreased by
tumor necrosis factor-alpha,
glucocorticoids,
beta-adrenergic agonists and cAMP. Data for
insulin are somewhat inconclusive. Moreover,
adiponectin expression and secretion are increased by activators of
peroxisome proliferator-activated receptor (
PPAR)-gamma. Besides inhibiting inflammatory pathways, recombinant
adiponectin increases
insulin sensitivity and improves
glucose tolerance in various animal models. This
insulin-sensitizing effect appears to be mostly attributable to enhanced suppression of
glucose production, but beneficial effects on muscle cannot be excluded. In humans, plasma
adiponectin concentrations exceed those of any other
hormone by a thousand times; they decrease with
obesity and are positively associated with whole-body
insulin sensitivity. Therefore, low
adiponectin may contribute to the decrease in whole-body
insulin sensitivity that accompanies
obesity. Furthermore, there is increasing evidence that genetic variants in the
adiponectin gene itself and/or in genes encoding
adiponectin-regulatory
proteins--such as
PPAR-gamma--may be associated with
hypoadiponectinemia,
insulin resistance and
type 2 diabetes. This suggests that
adiponectin may reflect
PPAR-gamma activity in vivo. Finally, reversal or alleviation of
hypoadiponectinemia may represent a target for development of drugs improving
insulin sensitivity and
glucose tolerance.