<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut

The small intestine is the initial site of glucose absorption and thus represents the first of a continuum of events that modulate normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabol...

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Autores principales:	Yue Li, Weidong Wang, Hui-Ying Lim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	solute carrier SGLT1 glucose transporter glucose metabolism intestinal absorption Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/0f5a98a6eba442f38362e6a1c99b1727
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spelling	oai:doaj.org-article:0f5a98a6eba442f38362e6a1c99b17272021-11-25T17:56:31Z<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut10.3390/ijms2222124241422-00671661-6596https://doaj.org/article/0f5a98a6eba442f38362e6a1c99b17272021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12424https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The small intestine is the initial site of glucose absorption and thus represents the first of a continuum of events that modulate normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. Using molecular genetic approaches, we investigated the role of <i>Drosophila</i> Solute Carrier 5A5 (dSLC5A5) in regulating glucose homeostasis by mediating glucose uptake in the fly midgut. By genetically knocking down <i>dSLC5A5</i> in flies, we found that systemic and circulating glucose and trehalose levels are significantly decreased, which correlates with an attenuation in glucose uptake in the enterocytes. Reciprocally, overexpression of dSLC5A5 significantly increases systemic and circulating glucose and trehalose levels and promotes glucose uptake in the enterocytes. We showed that dSLC5A5 undergoes apical endocytosis in a dynamin-dependent manner, which is essential for glucose uptake in the enterocytes. Furthermore, we showed that the dSLC5A5 level in the midgut is upregulated by glucose and that dSLC5A5 critically directs systemic glucose homeostasis on a high-sugar diet. Together, our studies have uncovered the first <i>Drosophila</i> glucose transporter in the midgut and revealed new mechanisms that regulate glucose transporter levels and activity in the enterocyte apical membrane.Yue LiWeidong WangHui-Ying LimMDPI AGarticlesolute carrierSGLT1glucose transporterglucose metabolismintestinal absorptionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12424, p 12424 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	solute carrier SGLT1 glucose transporter glucose metabolism intestinal absorption Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	solute carrier SGLT1 glucose transporter glucose metabolism intestinal absorption Biology (General) QH301-705.5 Chemistry QD1-999 Yue Li Weidong Wang Hui-Ying Lim <i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
description	The small intestine is the initial site of glucose absorption and thus represents the first of a continuum of events that modulate normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. Using molecular genetic approaches, we investigated the role of <i>Drosophila</i> Solute Carrier 5A5 (dSLC5A5) in regulating glucose homeostasis by mediating glucose uptake in the fly midgut. By genetically knocking down <i>dSLC5A5</i> in flies, we found that systemic and circulating glucose and trehalose levels are significantly decreased, which correlates with an attenuation in glucose uptake in the enterocytes. Reciprocally, overexpression of dSLC5A5 significantly increases systemic and circulating glucose and trehalose levels and promotes glucose uptake in the enterocytes. We showed that dSLC5A5 undergoes apical endocytosis in a dynamin-dependent manner, which is essential for glucose uptake in the enterocytes. Furthermore, we showed that the dSLC5A5 level in the midgut is upregulated by glucose and that dSLC5A5 critically directs systemic glucose homeostasis on a high-sugar diet. Together, our studies have uncovered the first <i>Drosophila</i> glucose transporter in the midgut and revealed new mechanisms that regulate glucose transporter levels and activity in the enterocyte apical membrane.
format	article
author	Yue Li Weidong Wang Hui-Ying Lim
author_facet	Yue Li Weidong Wang Hui-Ying Lim
author_sort	Yue Li
title	<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
title_short	<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
title_full	<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
title_fullStr	<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
title_full_unstemmed	<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut
title_sort	<i>drosophila</i> solute carrier 5a5 regulates systemic glucose homeostasis by mediating glucose absorption in the midgut
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0f5a98a6eba442f38362e6a1c99b1727
work_keys_str_mv	AT yueli idrosophilaisolutecarrier5a5regulatessystemicglucosehomeostasisbymediatingglucoseabsorptioninthemidgut AT weidongwang idrosophilaisolutecarrier5a5regulatessystemicglucosehomeostasisbymediatingglucoseabsorptioninthemidgut AT huiyinglim idrosophilaisolutecarrier5a5regulatessystemicglucosehomeostasisbymediatingglucoseabsorptioninthemidgut
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<i>Drosophila</i> Solute Carrier 5A5 Regulates Systemic Glucose Homeostasis by Mediating Glucose Absorption in the Midgut

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