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Introduction and pancreas and stomach (B) were perfused at severe hypoglycemia (glucose 1.5mM). Ach 1 µM, Ach 1 µM + GLP-1 (7-36) 1nM and GLP-1 (7-36) 1nM were sequentially infused (A: n = 6; B: n = 6). L-Arginine 10 mM was infused at the end of all experiments (positive control). Glucagon and SST levels were measured. Total hormone output was calculated. Statistical significance was settled at p0.05. Results: During hypoglycemia, cholinergic stimulation suppresses SST and stimulates glucagon secretion. Active GLP-1 (7-36) overrides cholinergic activity by potentiating SST and suppressing glucagon secretion in the isolated pancreas (A), but GLP-1 (7-36) has no effect if the vagus nerve integrity is preserved (B). Once cholinergic stimulation is discontinued, GLP-1 (7-36) suppresses glucagon and stimulates SST secretion in both preparations. Conclusion: Pancreatic cholinergic activity stimulates glucagon secretion during hypoglycemia through suppression of somatostatin secretion. Cholinergic signaling that is delivered through the gastric intramural autonomic ganglia and/or vagus nerve efferents to the pancreas is crucial for blunting GLP-1 (7-36) activity under hypoglycemia. These findings improve our understanding of GLP-1 physiology and shine light on the requirements to target vagal nerve function in optimizing pancreatic endocrine secretion. Disclosure C.B. Lobato: Research Support; Dexcom, Inc. J.J. Holst: Advisory Panel; Novo Nordisk A/S, Merck Sharp Antag Therapeutics. Funding Danish Diabetes Academy (NNF17SA0031406); "la Caixa" Foundation (LCF/BQ/EU21/11890081).
Lobato et al. (Fri,) studied this question.