Diabetologia co-auth.: B.Thorens

GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion

Nikhil R Gandasi 1 2Rui Gao 3Lakshmi Kothegala 1Abigail Pearce 4Cristiano Santos 1Samuel Acreman 1 3Davide Basco 5Anna Benrick 1Margarita V Chibalina 3Anne Clark 3Claudia Guida 3Matthew Harris 4Paul R V Johnson 6 7Jakob G Knudsen 8Jinfang Ma 3Caroline Miranda 1 3Makoto Shigeto 3Andrei I Tarasov 3 9Ho Yan Yeung 4Bernard Thorens 5Ingrid W Asterholm 1Quan Zhang 3Reshma Ramracheya 3Graham Ladds 4Patrik Rorsman 10 11 12 13

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Aims/hypothesis: Diabetes mellitus is associated with impaired insulin secretion, often aggravated by oversecretion of glucagon. Therapeutic interventions should ideally correct both defects. Glucagon-like peptide 1 (GLP-1) has this capability but exactly how it exerts its glucagonostatic effect remains obscure. Following its release GLP-1 is rapidly degraded from GLP-1(7-36) to GLP-1(9-36). We hypothesised that the metabolite GLP-1(9-36) (previously believed to be biologically inactive) exerts a direct inhibitory effect on glucagon secretion and that this mechanism becomes impaired in diabetes.