
Hindrik Mulder
Principal investigator

Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase
Author
Summary, in English
Glucagon-like peptide 1 (GLP-1), secreted from intestinal L cells, glucose dependently stimulates insulin secretion from β-cells. This glucose dependence prevents hypoglycemia, rendering GLP-1 analogs a useful and safe treatment modality in type 2 diabetes. Although the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear. We investigated how GLP-1 secretion is metabolically coupled in L cells (GLUTag) and in vivo inmice using the insulin-secreting cell line INS-1 832/13 as reference. A membrane-permeable glutamate analog (dimethylglutamate [DMG]), acting downstream of electrogenic transporters, elicited similar alterations in metabolism as glutamine in both cell lines. Both DMG and glutamine alone elicited GLP-1 secretion in GLUTag cells and in vivo, whereas activation of glutamate dehydrogenase (GDH) was required to stimulate insulin secretion from INS-1 832/13 cells. Pharmacological inhibition in vivo of GDH blocked secretion of GLP-1 in response to DMG. In conclusion, our results suggest that nonelectrogenic nutrient uptake and metabolism play an important role in L cell stimulus-secretion coupling. Metabolism of glutamine and related analogs by GDH in the L cell may explain why GLP-1 secretion, but not that of insulin, is activated by these secretagogues in vivo.
Department/s
- Diabetes - Molecular Metabolism
- Neuroendocrine Cell Biology
- Centre for Analysis and Synthesis
- Genomics, Diabetes and Endocrinology
- EXODIAB: Excellence of Diabetes Research in Sweden
Publishing year
2018-03-01
Language
English
Pages
372-384
Publication/Series
Diabetes
Volume
67
Issue
3
Document type
Journal article
Publisher
American Diabetes Association Inc.
Topic
- Endocrinology and Diabetes
Status
Published
Research group
- Diabetes - Molecular Metabolism
- Neuroendocrine Cell Biology
- Genomics, Diabetes and Endocrinology
ISBN/ISSN/Other
- ISSN: 0012-1797