The effect of fasting on sodium-dependent glucose absorption in the mouse proximal small intestine

Abstract

Abstract Caloric restriction and intermittent fasting are known to alter the function of various organs and the mechanisms of glucose metabolism, which affect health outcomes and slow aging. However, it remains unclear how short-term fasting affects glucose absorption function in the small intestine. We studied the effects of the short-term fasting on glucose-induced short-circuit current (Isc) in vitro using an Ussing chamber technique. Glucose-induced Isc by SGLT1 was observed in the ileum, but little or no Isc was observed in the jejunum in ad libitum-fed mice. However, in mice fasted for 24–48 hours, in addition to the ileum, robust glucose-induced Isc was observed over time in the jejunum. An increase in Na+ permeability between epithelial cells was concomitantly observed in the jejunum of fasted mice. Transepithelial glucose flux was assessed using a non-metabolizable glucose analog, 14C-methyl α-D-glucopyranoside glucose (MGP). Regardless of whether fed or fasted, no glucose diffusion mechanism was observed. Fasting increased the SGLT1-mediated MGP flux in the jejunum. In conclusion, fasting resulted in a selective increase in SGLT1 transport activity and Na⁺ selectivity at tight junctions in the jejunum, but not in the ileum. This segment dependent upregulation during fasting is important for efficient glucose absorption after the fast is broken.