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Tetrahydrocurcumin Upregulates the Adiponectin-AdipoR Pathway and Improves Insulin Signaling and Pancreatic β-Cell Function in High-Fat Diet/Streptozotocin-Induced Diabetic Obese Mice.

Abstract
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.
AuthorsYi-Zhen Tsai, Mei-Ling Tsai, Li-Yin Hsu, Chi-Tang Ho, Ching-Shu Lai
JournalNutrients (Nutrients) Vol. 13 Issue 12 (Dec 19 2021) ISSN: 2072-6643 [Electronic] Switzerland
PMID34960104 (Publication Type: Journal Article)
Chemical References
  • Adiponectin
  • Hypoglycemic Agents
  • Insulin
  • Receptors, Adiponectin
  • tetrahydrocurcumin
  • Streptozocin
  • Curcumin
Topics
  • Adiponectin (metabolism)
  • Animals
  • Apoptosis (drug effects)
  • Curcumin (analogs & derivatives, pharmacology, therapeutic use)
  • Diabetes Mellitus, Experimental (drug therapy, etiology, metabolism, physiopathology)
  • Diet, High-Fat (adverse effects)
  • Hypoglycemic Agents
  • Insulin (metabolism)
  • Insulin-Secreting Cells (metabolism, physiology)
  • Liver (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phytotherapy
  • Receptors, Adiponectin (metabolism)
  • Signal Transduction (drug effects)
  • Streptozocin
  • Up-Regulation (drug effects)

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