Islets were isolated as previously described (Melli et al., 2009 (link); Friedman et al., 2014 (link)). Briefly, mice were anesthetized with ketamine/xylazine before cervical dislocation. The pancreas was inflated via the common bile duct by adding ∼3 ml of 0.8 mg/ml Collagenase P (Roche) and 10 µg/ml DNase I (Roche) or CIzyme RI (Vitacyte) in HBSS (Cellgro). Following inflation, the pancreas was removed and incubated at 37°C for 10–11 min for Collagenase P digestion or 17 min for CIzyme RI digestion, and islets were isolated by density centrifugation. Islets were handpicked under a dissecting microscope. For experiments in which islets were analyzed using flow cytometry, single-cell suspensions were generated by digestion with 0.4 Wunsch units/ml Collagenase D (Roche) and 250 µg/ml DNase I (Roche) in HBSS (Cellgro) with 10% FBS (Hyclone) at 37°C for 30 min. Following initial digestion, islets were then incubated in Cell Dissociation Buffer (Sigma-Aldrich) at 37°C for an additional 30 min.