{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:11:11Z","timestamp":1791231071094,"version":"4.1.0"},"reference-count":122,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alpha cells in the pancreas, traditionally known for their role in secreting glucagon to regulate blood glucose levels, are gaining recognition for their involvement in the pathophysiology of type 1 diabetes (T1D). In T1D, autoimmune destruction of beta cells results in insulin deficiency, which in turn may dysregulate alpha cell function, leading to elevated glucagon levels and impaired glucose homeostasis. This dysfunction is characterized by inappropriate glucagon secretion, augmenting the risk of life-threatening hypoglycemia. Moreover, insulin deficiency and autoimmunity alter alpha cell physiological responses, further exacerbating T1D pathophysiology. Recent studies suggest that alpha cells undergo transdifferentiation and interact with beta cells through mechanisms involving gamma-aminobutyric acid (GABA) signaling. Despite these advances, the exact pathways and interactions remain poorly understood and are often debated. Understanding the precise role of alpha cells in T1D is crucial, as it opens up avenues for developing new therapeutic strategies for T1D. Potential strategies include targeting alpha cells to normalize glucagon secretion, utilizing glucagon receptor antagonists, enhancing GABA signaling, and employing glucagon-like peptide-1 (GLP-1) receptor agonists. These approaches aim to improve glycemic control and reduce the risk of hypoglycemic events in individuals with T1D. This review provides an overview of alpha cell function in T1D, highlighting the emerging focus on alpha cell dysfunction in the context of historically well-developed beta cell research.<\/jats:p>","DOI":"10.3390\/cells13221914","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T06:06:54Z","timestamp":1731996414000},"page":"1914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Decoding the Significance of Alpha Cell Function in the Pathophysiology of Type 1 Diabetes"],"prefix":"10.3390","volume":"13","author":[{"given":"Jordan","family":"Carroll","sequence":"first","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"Chen","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Mittal","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-1617","authenticated-orcid":false,"given":"Joana R. N.","family":"Lemos","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mannat","family":"Mittal","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Juneja","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7115-5945","authenticated-orcid":false,"given":"Amro","family":"Assayed","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khemraj","family":"Hirani","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/S0140-6736(23)00223-4","article-title":"Type 1 diabetes","volume":"401","author":"Quattrin","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"Itc33","DOI":"10.7326\/AITC202203150","article-title":"Type 1 Diabetes Mellitus","volume":"175","author":"Syed","year":"2022","journal-title":"Ann. 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