TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression

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Abstract: To fulfill their function, pancreatic beta cells require precise nutrient‐sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta‐cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene expression in response to amino acid deprivation. Interestingly, ChIP‐seq analysis showed binding of TFEB to super‐enhancer regions that regulate insulin transcription. Conditional, beta‐cell‐specific, Tfeb‐overexpressing, and Tfeb/Tfe3 double‐KO mice showed severe alteration of insulin transcription, secretion, and glucose tolerance, indicating that TFEB and TFE3 are important physiological mediators of pancreatic function. Our findings reveal a nutrient‐controlled transcriptional mechanism that regulates insulin production, thus playing a key role in glucose homeostasis at both cellular and organismal levels.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression ; day:15 ; month:09 ; year:2023 ; extent:19
The EMBO journal / European Molecular Biology Organization ; (15.09.2023) (gesamt 19)

Creator: Pasquier, Adrien
Pastore, Nunzia
D'Orsi, Luca
Colonna, Rita
Esposito, Alessandra
Maffia, Veronica
De Cegli, Rossella
Mutarelli, Margherita
Ambrosio, Susanna
Tufano, Gennaro
Grimaldi, Antonio
Cesana, Marcella
Cacchiarelli, Davide
Delalleau, Nathalie
Napolitano, Gennaro
Ballabio, Andrea

DOI: 10.15252/embj.2023113928

URN: urn:nbn:de:101:1-2023091515223612442915

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 10:49 AM CEST

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Associated

Pasquier, Adrien
Pastore, Nunzia
D'Orsi, Luca
Colonna, Rita
Esposito, Alessandra
Maffia, Veronica
De Cegli, Rossella
Mutarelli, Margherita
Ambrosio, Susanna
Tufano, Gennaro
Grimaldi, Antonio
Cesana, Marcella
Cacchiarelli, Davide
Delalleau, Nathalie
Napolitano, Gennaro
Ballabio, Andrea

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TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression

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Other Objects (12)

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SIRT5 is important for bacterial infection by regulating insulin secretion and glucose homeostasis

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Checkpoint kinase 2 controls insulin secretion and glucose homeostasis

Non-insulin determinant pathways maintain glucose homeostasis upon metabolic surgery

BACH1 controls hepatic insulin signaling and glucose homeostasis in mice

USF2 and TFEB compete in regulating lysosomal and autophagy genes

TFEB controls vascular development by regulating the proliferation of endothelial cells

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Impact of exercise on glucose homeostasis in different mouse models for impaired insulin sensitivity

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Checkpoint kinase 2 controls insulin secretion and glucose homeostasis

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Impact of exercise on glucose homeostasis in different mouse models for impaired insulin sensitivity

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