In animal models with obesity and T2DM, hyperinsulinemia promotes profibrogenic signals in HSCs via the stimulation of connective tissue growth factor (CTGF) mRNA transcription, either directly or as a co-factor of transforming growth factor-beta (TGF-β) [45], while results from another study demonstrated that TGF-β-mediated CTGF expression in HSCs requires signal transducer and activator of transcription 3 (STAT3) signaling activation [46]. This evidence concerns the gene CCN2 and type 2 diabetes mellitus.