Clocking up GLP-1: considering intestinal rhythms in the incretin effect.

Abstract

Pancreatic β-cells, like many other cells, contain autonomous circadian oscillators, the disruption of which leads to hypoinsulinemia and hyperglycemia in mice (1,2). Rather than slavishly following the master clock located in the suprachiasmatic nuclei, which synchronize internal oscillations with the external light-dark cycle, some peripheral clocks, including the one in the endocrine pancreas, can be reset by alternative clues, such as time-restricted food availability. The way that this food “entrainment” works has remained unclear. GLP-1, an incretin hormone that boosts glucose-dependent insulin secretion, is a candidate messenger that could potentially coordinate peripheral oscillators with the timing of food arrival in the gut. In this issue of Diabetes , Gil-Lozano et al. (3) investigated the influence of the day-night cycle on the GLP-1 axis. To circumvent interference from previous meals, Gil-Lozano et al. fasted rats for 4 h before applying oral glucose tolerance tests (OGTTs) at intervals throughout the day. They observed clear 24-h rhythmicity of plasma GLP-1 concentrations that were in phase with insulin levels. Interestingly, the strongest responses were observed toward the end of the lights-on period—a time when nocturnal rats allowed to consume food freely do not usually eat much. The circadian rhythm of plasma glucose responses had a higher frequency, possibly reflecting the 12-h period reported for hepatic metabolic cycles (4). To test if the observed diurnal rhythm of GLP-1 responses was food entrainable, rats were accustomed to feed only during the dark or the light phase. Dark-fed rats, like their free-feeding counterparts, had a more …