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Dysregulation of the alpha cell and glucagon release is a hallmark of type 1 diabetes.Impaired regulation of pancreatic peptides, such as somatostatin and neuronostatin, can contribute to alpha cell dysregulation.Alpha cell dysfunction is a progressive phenomenon that is associated with progressive loss of glucagon regulation.Type 1 diabetes is characterized by selective loss of beta cells and insulin secretion, which significantly impact glucose homeostasis. However, this progressive disease is also associated with dysfunction of the alpha cell component of the islet, which can exacerbate hyperglycemia due to paradoxical hyperglucagonemia or lead to severe hypoglycemia as a result of failed counterregulation. In this review, the physiology of alpha cell secretion and the potential mechanisms underlying alpha cell dysfunction in type 1 diabetes will be explored. Because type 1 diabetes is a progressive disease, a synthesized timeline of aberrant alpha cell function will be presented as an attempt to delineate the natural history of type 1 diabetes with respect to the alpha cell.