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Suppression of Insulin Production and Secretion by a Decretin Hormone
Open accessAbstract
Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia, and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila ortholog of Neuromedin U receptors (NMURs), in insulin-producing cells phenocopied limostatin deficiency and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output.
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“In addition to this, NmU is likely to regulate insulin secretion; the G-protein-coupled NmU receptor 1 (NmUR1) is expressed in pancreatic islets and its simulation dose dependently decreased insulin release.230, 231”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [231]
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“Moreover, knockdown of the fly NmUR orthologue not only reproduced the consequences of limostatin deficiency but also diminished its insulin-suppressing ability.”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [231]
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“A very recent study showed231 that the peptide hormone limostatin, which is expressed in Drosophila melanogaster, also reduces insulin secretion and its absence caused hyperinsulinemia, hypoglycemia and obesity.”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [231]
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Metadata
- Authors
- Alfa, R. W., Park, S., Skelly, K.-R., Poffenberger, G., Jain, N., Gu, X., Kockel, L., Wang, J., Liu, Y., Powers, A. C., & Kim, S. K.
- Affiliations
- Stanford Medicine (US)
- Vanderbilt University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kim, Seung K.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 21
- Issue
- 2
- Pages
- 323-334
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4349554
- OpenAlex
- W2071073520
- Cited by
- 150
- References
- 70
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 10 · 2023: 3 · 2022: 12 · 2021: 19 · 2020: 14 · 2019: 16 · 2018: 11 · 2017: 9 · 2016: 24 · 2015: 9
- FWCI
- 17.79
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-02-06)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5p60dk020593-31)
- Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center
- National Institute of Mental Health (T32MH020016)
- National Institute of General Medical Sciences (R01GM084947)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK020593, U01DK089572, DK-89572, DK072473, DK 20593, UC4DK104211, U01DK072473, P30DK020593)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- insulin secretion, insulin production, neuromedin U, insulin-producing cells, gastrointestinal endocrine cells, nutrient restriction, hyperinsulinemia, hypoglycemia, adiposity, Drosophila, pancreatic beta cells, peptide hormone receptors
- MeSH terms
- Insulin Secretion, Adult, Animals, Child, Preschool, Drosophila, Hormones, Humans, Insulin, Islets of Langerhans, Middle Aged, Neuropeptides, Receptors, Neurotransmitter, Drosophila Proteins, Peptide Hormones, Endocrine Cells, Young Adult
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