Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i>
The insulin−IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells i...
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MDPI AG
2020-03-01
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| Series: | Cells |
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| author | Olha M. Strilbytska Uliana V. Semaniuk Kenneth B. Storey Ihor S. Yurkevych Oleh Lushchak |
| author_facet | Olha M. Strilbytska Uliana V. Semaniuk Kenneth B. Storey Ihor S. Yurkevych Oleh Lushchak |
| author_sort | Olha M. Strilbytska |
| collection | DOAJ |
| description | The insulin−IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in <i>Drosophila melanogaster</i>, namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the <i>Drosophila</i> transcripts for the insulin-like peptides <i>dilp2</i>, <i>dilp5</i>, and <i>dilp6.</i> This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene (<i>tobi</i>). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, <i>Pten</i> knockdown to enhance IIS also activated JAK−STAT signaling in gut tissue by up-regulation of <i>upd2</i>, <i>upd3</i>, and <i>soc36 </i>genes, as well as genes encoding the EGF receptor ligands <i>spitz</i> and <i>vein</i>. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival. |
| first_indexed | 2024-03-12T07:44:23Z |
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| language | English |
| last_indexed | 2024-03-12T07:44:23Z |
| publishDate | 2020-03-01 |
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| series | Cells |
| spelling | doaj.art-4e309a923d874bbbb02a3ec1aa39fa422023-09-02T21:05:45ZengMDPI AGCells2073-44092020-03-019480310.3390/cells9040803cells9040803Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i>Olha M. Strilbytska0Uliana V. Semaniuk1Kenneth B. Storey2Ihor S. Yurkevych3Oleh Lushchak4Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., 76018 Ivano-Frankivsk, UkraineDepartment of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., 76018 Ivano-Frankivsk, UkraineInstitute of Biochemistry, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., 76018 Ivano-Frankivsk, UkraineDepartment of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., 76018 Ivano-Frankivsk, UkraineThe insulin−IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in <i>Drosophila melanogaster</i>, namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the <i>Drosophila</i> transcripts for the insulin-like peptides <i>dilp2</i>, <i>dilp5</i>, and <i>dilp6.</i> This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene (<i>tobi</i>). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, <i>Pten</i> knockdown to enhance IIS also activated JAK−STAT signaling in gut tissue by up-regulation of <i>upd2</i>, <i>upd3</i>, and <i>soc36 </i>genes, as well as genes encoding the EGF receptor ligands <i>spitz</i> and <i>vein</i>. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival.https://www.mdpi.com/2073-4409/9/4/803insulin signaling pathwaymidgutiscprogenitor cellslifespanmetabolismfruit fly |
| spellingShingle | Olha M. Strilbytska Uliana V. Semaniuk Kenneth B. Storey Ihor S. Yurkevych Oleh Lushchak Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i> Cells insulin signaling pathway midgut isc progenitor cells lifespan metabolism fruit fly |
| title | Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i> |
| title_full | Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i> |
| title_fullStr | Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i> |
| title_full_unstemmed | Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i> |
| title_short | Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in <i>Drosophila</i> |
| title_sort | insulin signaling in intestinal stem and progenitor cells as an important determinant of physiological and metabolic traits in i drosophila i |
| topic | insulin signaling pathway midgut isc progenitor cells lifespan metabolism fruit fly |
| url | https://www.mdpi.com/2073-4409/9/4/803 |
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