As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.

Key Points: Transplanted kidneys with multiple arteries have similar delayed graft function and 90-day graft failure compared with single-artery kidneys. Deceased donor kidneys with multiple renal arteries have a longer cold ischemia time at transplantation compared with those with single arteries. Kidneys needing spatulation to single anastomoses may experience more delayed graft function than single-artery or other multiartery kidneys. Background: Anatomic abnormalities increase the risk of deceased donor kidney discard, but their effect on transplant outcomes is understudied. We sought to determine the effect of multiple donor renal arteries on early outcomes after deceased donor kidney transplantation. Methods: For this retrospective cohort study, we identified 1443 kidneys from 832 deceased donors with ≥1 kidney transplanted at our center (2006–2016). We compared the odds of delayed graft function and 90-day graft failure using logistic regression. To reduce potential selection bias, we then repeated the analysis using a paired-kidney cohort, including kidney pairs from 162 donors with one single-artery kidney and one multiartery kidney. Results: Of 1443 kidneys included, 319 (22%) had multiple arteries. Multiartery kidneys experienced longer cold ischemia time, but other characteristics were similar between groups. Delayed graft function (50% multiartery versus 45% one artery, P=0.07) and 90-day graft failure (3% versus 3%, P=0.83) were similar between groups before and after adjusting for donor and recipient characteristics. In the paired kidney analysis, cold ischemia time was significantly longer for multiartery kidneys compared with single-artery kidneys from the same donor (33.5 versus 26.1 hours, P<0.001), but delayed graft function and 90-day graft failure were again similar between groups. Conclusions: Compared with single-artery deceased donor kidneys, those with multiple renal arteries are harder to place, but experience similar delayed graft function and early graft failure.

Coronavirus disease 2019 (COVID‐19) has become a pandemic since first being described in January 2020. Clinical manifestations in non‐transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID‐19 infection occurring in pancreas transplant recipients.