MedStar Authors catalog › Details for: The Role of the alpha Cell in the Pathogenesis of Diabetes: A World beyond the Mirror. [Review]
The Role of the alpha Cell in the Pathogenesis of Diabetes: A World beyond the Mirror. [Review] Journal: International journal of molecular sciences.Published: 2021; ; ISSN: 1422-0067.UI/PMID: 34502413.Subject(s): *Autocrine Communication | *Diabetes Mellitus, Type 1/me [Metabolism] | *Diabetes Mellitus, Type 2/me [Metabolism] | *Glucagon-Secreting Cells/me [Metabolism] | *Insulin-Secreting Cells/me [Metabolism] | *Paracrine Communication | Animals | Diabetes Mellitus, Type 1/dt [Drug Therapy] | Diabetes Mellitus, Type 1/pa [Pathology] | Diabetes Mellitus, Type 2/dt [Drug Therapy] | Diabetes Mellitus, Type 2/pa [Pathology] | Dipeptidyl-Peptidase IV Inhibitors/tu [Therapeutic Use] | Glucagon-Like Peptide 1/ai [Antagonists & Inhibitors] | Glucagon-Like Peptide 1/me [Metabolism] | Glucagon-Secreting Cells/pa [Pathology] | Glucagon/me [Metabolism] | Humans | Hypoglycemic Agents/tu [Therapeutic Use] | Insulin-Secreting Cells/pa [Pathology]Institution(s): MedStar Washington Hospital CenterDepartment(s): Medicine/Internal MedicineActivity type: Journal Article.Medline article type(s): Journal Article | ReviewDigital Object Identifier: https://dx.doi.org/10.3390/ijms22179504 (Click here) Abbreviated citation: Int. j. mol. sci.. 22(17), 2021 Sep 01; .Abstract: Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (alpha) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic alpha cell mass or dysfunction in glucagon's secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans' islets cytoarchitecture, including alpha cell hyperplasia, pancreatic beta (beta) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to beta cell mass loss. Other abnormalities like alpha cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.