Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase
(2018) In Diabetes 67(3). p.372-384- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2018-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 67
- issue
- 3
- pages
- 13 pages
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:29229616
- scopus:85042590210
- ISSN
- 0012-1797
- DOI
- 10.2337/db16-1441
- language
- English
- LU publication?
- yes
- id
- c233f0c4-c320-49b2-97e6-9aefeff27d51
- date added to LUP
- 2018-03-17 18:54:56
- date last changed
- 2024-06-24 11:30:16
@article{c233f0c4-c320-49b2-97e6-9aefeff27d51, abstract = {{<p>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.</p>}}, author = {{Andersson, Lotta E. and Shcherbina, Liliya and Al-Majdoub, Mahmoud and Vishnu, Neelanjan and Arroyo, Claudia Balderas and Carrara, Jonathan Aste and Wollheim, Claes B. and Fex, Malin and Mulder, Hindrik and Wierup, Nils and Spégel, Peter}}, issn = {{0012-1797}}, language = {{eng}}, month = {{03}}, number = {{3}}, pages = {{372--384}}, publisher = {{American Diabetes Association Inc.}}, series = {{Diabetes}}, title = {{Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase}}, url = {{http://dx.doi.org/10.2337/db16-1441}}, doi = {{10.2337/db16-1441}}, volume = {{67}}, year = {{2018}}, }