Impairment of
adiponectin production and function is closely associated with
insulin resistance and
type 2 diabetes, which are linked to
obesity. Studies in animal models have documented the anti-diabetic effects of
tetrahydrocurcumin (
THC). Although several possible mechanisms have been proposed, the contribution of
adiponectin signaling on
THC-mediated
antihyperglycemic effects remains unknown. Here, we report that adiposity, steatosis, and
hyperglycemia were potently attenuated in high-fat diet/
streptozotocin-induced diabetic obese mice after they received 20 and 100 mg/kg
THC for 14 weeks.
THC upregulated UCP-1 in adipose tissue and elevated
adiponectin levels in the circulation.
THC upregulated the AdipoR1/R2-APPL1-mediated pathway in the liver and skeletal muscle, which contributes to improved
insulin signaling,
glucose utilization, and lipid metabolism. Furthermore,
THC treatment significantly (p < 0.05) preserved islet mass, reduced apoptosis, and restored defective
insulin expression in the pancreatic β-cells of diabetic obese mice, which was accompanied by an elevation of AdipoR1 and APPL1. These results demonstrated a potential mechanism underlying the beneficial effects of
THC against
hyperglycemia via the
adiponectin-AdipoR pathway, and thus, may lead to a novel
therapeutic use for
type 2 diabetes.