Format

Send to

Choose Destination
Cell Metab. 2015 Feb 3;21(2):323-334. doi: 10.1016/j.cmet.2015.01.006.

Suppression of insulin production and secretion by a decretin hormone.

Author information

1
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Neuroscience Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
4
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
5
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
6
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: seungkim@stanford.edu.

Abstract

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.

PMID:
25651184
PMCID:
PMC4349554
DOI:
10.1016/j.cmet.2015.01.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center