TNF and obesity due to melanocortin 4 receptor deficiency: To investigate whether the improved glucose clearance in TKO-IFSD compared with TWT-IFSD mice was due to the improved survival of beta cells in response to intra-islet low-grade inflammation usually observed in obesity, we exposed isolated TWT and TKO islets (S5B Fig) to IL-1β or a combination of IL-1β, IFN-γ, and TNF-α (cytomix) for 24 h and measured apoptosis (Fig 5F).