Furthermore, cholecystokinin-8, a gut hormone that potentiates GSIS, has been shown to increase PPP activity in pancreatic islets53,54; in clinical settings, G6PD deficiency is associated with an increase in the prevalence of T2D (ref. 55) and G6PD activities are reduced in T2D (ref. 56); patients with G6PD deficiency also have reduced insulin response to IVGTT57 and impaired fasting glucose40,51,58,59. Here, INS is linked to type 2 diabetes mellitus.