I n this issue of the JCI, Morioka et al. report on mice with a whole-pancreas knockout of the leptin receptor that exhibit improved glucose tolerance due to enhanced insulin secretion (see the related article beginning on page 2860). At first glance, their findings are very different from those reported in another recent study in which β cell–specific and hypothalamic knockout of the same gene caused obesity and impaired β cell function. The differences, which are understandable when one considers the body weights of the animals studied, provide new insight into the links among insulin, leptin action, and β cell function.