Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice.

•Curcumin reduced cAMP accumulation by protecting PDE4B activity from inflammation.•Preserving PDE4B activity reduced cAMP accumulation in response to glucagon response.•Curcumin lowed fasting blood glucose via restraining endogenous glucose production.•Curcumin reduced hepatic acetyl CoA accumulation via limiting fatty acid oxidation.•Reducing hepatic acetyl CoA protected PDH activity and inhibited PC induction.