Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding

Abstract Fasting is 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 fasting and feeding affects glucose absorption function in the small intestine. We studied the effects of the fasti...

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Main Authors: Chisato Nakamura, Noriko Ishizuka, Kanako Yokoyama, Yuyu Yazaki, Fumiya Tatsumi, Naotaka Ikumi, Wendy Hempstock, Akira Ikari, Yuta Yoshino, Hisayoshi Hayashi
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-38024-w
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author Chisato Nakamura
Noriko Ishizuka
Kanako Yokoyama
Yuyu Yazaki
Fumiya Tatsumi
Naotaka Ikumi
Wendy Hempstock
Akira Ikari
Yuta Yoshino
Hisayoshi Hayashi
author_facet Chisato Nakamura
Noriko Ishizuka
Kanako Yokoyama
Yuyu Yazaki
Fumiya Tatsumi
Naotaka Ikumi
Wendy Hempstock
Akira Ikari
Yuta Yoshino
Hisayoshi Hayashi
author_sort Chisato Nakamura
collection DOAJ
description Abstract Fasting is 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 fasting and feeding affects glucose absorption function in the small intestine. We studied the effects of the fasting and feeding on glucose-induced short-circuit current (I sc ) in vitro using an Ussing chamber technique. Glucose-induced I sc by SGLT1 was observed in the ileum, but little or no I sc was observed in the jejunum in ad libitum-fed mice. However, in mice fasted for 24–48 h, in addition to the ileum, robust glucose-induced I sc was observed over time in the jejunum. The expression of SGLT1 in the brush border membranes was significantly decreased in the jejunum under fed conditions compared to 48 h fasting, as analyzed by western blotting. Additionally, when mice were fed a 60% high glucose diet for 3 days, the increase in glucose-induced I sc was observed only in the ileum, and totally suppressed 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, segment-dependent up- and down-regulation mechanisms during fasting and feeding are important for efficient glucose absorption once the fast is broken. Additionally, these mechanisms may play a crucial role in the small intestine's ability to autoregulate glucose absorption, preventing acute hyperglycemia when large amounts of glucose are ingested.
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spelling doaj.art-dac0b6d5579b492a891fe6f5617f2a692023-07-09T11:11:02ZengNature PortfolioScientific Reports2045-23222023-07-0113111710.1038/s41598-023-38024-wRegulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feedingChisato Nakamura0Noriko Ishizuka1Kanako Yokoyama2Yuyu Yazaki3Fumiya Tatsumi4Naotaka Ikumi5Wendy Hempstock6Akira Ikari7Yuta Yoshino8Hisayoshi Hayashi9Laboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaLaboratory of Biochemistry, Gifu Pharmaceutical UniversityLaboratory of Biochemistry, Gifu Pharmaceutical UniversityLaboratory of Physiology, Graduate School of Nutritional and Environmental Sciences, University of ShizuokaAbstract Fasting is 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 fasting and feeding affects glucose absorption function in the small intestine. We studied the effects of the fasting and feeding on glucose-induced short-circuit current (I sc ) in vitro using an Ussing chamber technique. Glucose-induced I sc by SGLT1 was observed in the ileum, but little or no I sc was observed in the jejunum in ad libitum-fed mice. However, in mice fasted for 24–48 h, in addition to the ileum, robust glucose-induced I sc was observed over time in the jejunum. The expression of SGLT1 in the brush border membranes was significantly decreased in the jejunum under fed conditions compared to 48 h fasting, as analyzed by western blotting. Additionally, when mice were fed a 60% high glucose diet for 3 days, the increase in glucose-induced I sc was observed only in the ileum, and totally suppressed 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, segment-dependent up- and down-regulation mechanisms during fasting and feeding are important for efficient glucose absorption once the fast is broken. Additionally, these mechanisms may play a crucial role in the small intestine's ability to autoregulate glucose absorption, preventing acute hyperglycemia when large amounts of glucose are ingested.https://doi.org/10.1038/s41598-023-38024-w
spellingShingle Chisato Nakamura
Noriko Ishizuka
Kanako Yokoyama
Yuyu Yazaki
Fumiya Tatsumi
Naotaka Ikumi
Wendy Hempstock
Akira Ikari
Yuta Yoshino
Hisayoshi Hayashi
Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
Scientific Reports
title Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
title_full Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
title_fullStr Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
title_full_unstemmed Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
title_short Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
title_sort regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
url https://doi.org/10.1038/s41598-023-38024-w
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