Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase

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title = "Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase",
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 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.",
author = "Andersson, {Lotta E.} and Liliya Shcherbina and Mahmoud Al-Majdoub and Neelanjan Vishnu and Arroyo, {Claudia Balderas} and Carrara, {Jonathan Aste} and Wollheim, {Claes B.} and Malin Fex and Hindrik Mulder and Nils Wierup and Peter Sp{\'e}gel",
year = "2018",
month = "3",
day = "1",
doi = "10.2337/db16-1441",
language = "English",
volume = "67",
pages = "372--384",
journal = "Diabetes",
issn = "1939-327X",
publisher = "American Diabetes Association Inc.",
number = "3",