Abstract: Aspects of the present disclosure are directed to methods and compositions for facilitating ?-cell regeneration by inhibition of the HIF1?-PFKFB3 pathway. Certain aspects describe methods for treatment and prevention of prediabetes and diabetes, including type 2 diabetes. Also disclosed are methods and compositions for enhancing ?-cell regeneration.

Abstract: A compound of formula I, or a pharmaceutically acceptable salt thereof, wherein —X1, X2 and X3 are each independently where Y is an alkylene, alkenylene or alkynylene group, each of which may be optionally substituted with one or more substituents selected from alkyl, halo, CF3, OH, alkoxy, NH2, CN, NO2 and COOH; W is absent or is O, S or NH; R1, R2, R3 and R4 are each independently selected from H, alkyl, aryl and a protecting group Pi; R7, R8 and R9 are each independently selected from H, alkyl, halo, CF3, OH, alkoxy, CN, NO2 and COOH; —q is 1, 2, 3 or 4; q? is 0, 1, 2 or 3, where q+q? equals 4; p and r are each independently 1, 2, 3, 4 or 5; p? and r? are each independently 0, 1, 2, 3 or 4, where p+p? and r+r? each equal 5; and —n is 0, 1, 2, 3, 4, 5 or 6.