Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice.
OBJECTIVE
This study is designed to investigate whether curcumin reduces excessive hepatic glucose production (HGP) via regulation of second messenger cAMP.


METHODS
High-fat diet (HFD)-fed mice were orally administrated of metformin (200 mg/kg) or curcumin (50 mg/kg) daily for 10 weeks. Meanwhile, we stimulated mouse primary hepatocytes with palmitate (PA).


RESULTS
Curcumin reduced hepatic cAMP accumulation by preserving PDE4B induction, thereby suppressing gluconeogenesis via blocking cAMP/PKA activation. Curcumin reduced lipid deposition by reducing free fatty acid uptake and prevented acetyl CoA accumulation by combating mitochondrial oxidation. As a result from inhibiting acetyl CoA accumulation, curcumin protected pyruvate dehydrogenase (PDH) activity and inhibited pyruvate carboxylase (PC), limiting the shift of mitochondrial pyruvate from oxidation to gluconeogenesis via the carboxylation.


CONCLUSION
Curcumin reduced cAMP accumulation by preserving PDE4B activity and inhibited acetyl CoA production by reducing mitochondrial fatty acid oxidation, thereby restraining pyruvate-driven hepatic glucose production.
['Wang|Zixia|Z|', 'Xu|Dan|D|', 'She|Linlin|L|', 'Zhang|Yirui|Y|', 'Wei|Qingli|Q|', 'Aa|Jiye|J|', 'Wang|Guangji|G|', 'Liu|Baolin|B|', 'Xie|Yuan|Y|']
D000105:Acetyl Coenzyme A D000263:Adenylate Kinase D000818:Animals D003474:Curcumin D000242:Cyclic AMP D017868:Cyclic AMP-Dependent Protein Kinases D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 D059305:Diet, High-Fat D004789:Enzyme Activation D005247:Feeding Behavior D005943:Gluconeogenesis D005947:Glucose D022781:Hepatocytes D006943:Hyperglycemia D050356:Lipid Metabolism D008099:Liver D008297:Male D008813:Mice, Inbred ICR D011766:Pyruvate Carboxylase D011768:Pyruvate Dehydrogenase Complex
Curcumin cAMP Acetyl CoA Gluconeogenesis