Suppression of insulin production and secretion by decretin hormones
Abstract/Contents
- Abstract
- Hormones induced by fasting that suppress insulin production and secretion have been postulated from classical studies of humans, but remain unidentified. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in Drosophila entero-endocrine corpora cardiaca (CC) cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia and excess triglycerides. A conserved 15-residue polypeptide encoded by limostatin was sufficient to suppress secretion by insulin-producing cells (IPCs). Targeted knockdown of the G-protein-coupled receptor encoded by CG9918 in IPCs phenocopied limostatin deficiency, nominating CG9918 as a Limostatin receptor. Mammalian Neuromedin U (NMU) receptor 1 is orthologous to CG9918 and expressed in islet cells. NMU-25 inhibits insulin secretion by human islets, but a human NMU mutant variant identified in a cohort with childhood-onset obesity fails to suppress secretion. Thus, Lst and NMU provide a molecular basis for decretin signaling in Drosophila and man.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Alfa, Ronald W |
|---|---|
| Associated with | Stanford University, Neurosciences Program. |
| Primary advisor | Kim, Seung K |
| Thesis advisor | Kim, Seung K |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Goodman, Miriam Beth |
| Thesis advisor | Lewis, Richard (Richard Sheridan) |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Advisor | Goodman, Miriam Beth |
| Advisor | Lewis, Richard (Richard Sheridan) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Ronald W. Alfa. |
|---|---|
| Note | Submitted to the Program in Neuroscience. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Ronald Alfa
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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