Emergence of Rheb as a promising therapeutic target in the amelioration of diabetes

Complications of diabetes have continued to escalate as a major public health concern worldwide. The situation keenly demands novel treatment strategies alongside the canonical regimen. Underscoring the molecular mechanisms associated with diabetic cellular pathophysiologies is very crucial in terms of therapeutics development. Ras homologue enriched in brain (Rheb) has recently emerged as a key controller for mechanistic (erstwhile mammalian) target of rapamycin complex 1 (mTORC1). The occurrence of different diseases including diabetes is attributed to augmented mTORC1 activation. Thus, investigation of the potential of Rheb as a therapeutic target has gained much interest recently. However, factors like difficulty in in vivo delivery, off-target effects, bioavailability issues, immunosuppressive effects, disruption of mTORC1-independent pathways involving Rheb, and many more, including the complicated nature of the disease diabetes itself, pose significant challenges in the development of Rheb therapeutics. The present article aims to shed light on the existing contribution of Rheb in the regulation of diabetic consequences and to rationalize its feasibility as a therapeutic target, with special emphasis on microRNA-mediated post-transcriptional regulation.