Figure 12.

Schematic showing that metformin alleviates hyperglycemia-induced endothelial impairment by downregulating autophagy via the Hedgehog pathway. Metformin treatment restores the hyperglycemia-impaired Hh pathway activity. And it is through GLI1, that metformin downregulates hyperglycemia-triggered BNIP3 expression, which subsequently inhibits the association between BNIP3 and BCL2, thus enhancing the binding of BECN1 and BCL2. In this way, hyperglycemia-triggered prolonged autophagy is inhibited by metformin, resulting in the alleviation of hyperglycemia-induced endothelial dysfunction.