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Pancreatic \u03b1 cells secrete glucagon that regulates amino acid catabolism through gluconeogenesis and ureagenesis, yet the mechanisms linking amino acid levels to \u03b1 cell growth and function are not fully understood. Here, we identify glutaminase, the enzyme that catalyzes glutamine catabolism, as a critical \u03b1 cell regulator. Glutaminase is highly enriched in \u03b1 cells across species. \u03b1 cell expression of glutaminase is required for nutrient-dependent mTORC1 activation, suppression of AMPK signaling, and sustained expression of the glutamine transporter SLC38A5. This establishes a feed-forward loop linking glutamine metabolism to amino acid sensing and growth. Reduced glutaminase activity impairs dynamic glucagon secretion in response to low glucose and amino acids. Together, these findings highlight the importance of glutamine metabolism in \u03b1 cell growth and hormone secretion and suggest it may play a role in \u03b1 cell adaptation to hyperaminoacidemia.<\/jats:p>","DOI":"10.64898\/2026.07.09.735845","type":"posted-content","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T20:40:19Z","timestamp":1783975219000},"source":"Crossref","is-referenced-by-count":0,"title":["Glutamine Metabolism Supports \u03b1 cell Mass and Glucagon Secretion"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8991-3882","authenticated-orcid":false,"given":"Anna Marie R.","family":"Schornack","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J.","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism, Department of 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