ArticleDiabetologia2022
Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation.
Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Aging Affects Pancreatic α-Cell Function and Promotes Hyperglucagonemia: Implications in Age-Associated Diabetes.Aging cell · 2026Article
- Chronic attenuation of brain leptin signalling is associated with early metabolic dysfunction in lean rats.The Journal of physiology · 2026Article
- Glucagon secretion by pancreatic alpha-cells requires an intact tubulin-cytoskeleton-primary cilium axis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Genetic and clinical investigation of insulin-degrading enzyme in Parkinson's disease within the Chinese Han population.Frontiers in neuroscience · 2026Article
- Effects of Saccharomyces cerevisiae on Pancreatic Alpha and Beta Cells and Metabolic Profile in Broilers.Probiotics and antimicrobial proteins · 2025Article
- Insulin-degrading enzyme confers neuroprotection in Parkinson's disease by inhibiting the Hippo signaling pathway.Cell death & disease · 2025Article
- Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon.Scientific reports · 2025Article
- Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head.Molecular medicine (Cambridge, Mass.) · 2024Article
- Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.iScience · 2024Article
- The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson's Disease Pathogenesis.Nutrients · 2023Review
- Primary Cilia in Pancreatic β- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme.Frontiers in endocrinology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
aims/hypothesisType 2 diabetes is characterised by hyperglucagonaemia and perturbed function of pancreatic glucagon-secreting alpha cells but the molecular mechanisms contributing to these phenotypes are poorly understood. Insulin-degrading enzyme (IDE) is present within all islet cells, mostly in alpha cells, in both mice and humans. Furthermore, IDE can degrade glucagon as well as insulin, suggesting that IDE may play an important role in alpha cell function in vivo.
methodsWe have generated and characterised a novel mouse model with alpha cell-specific deletion of Ide, the A-IDE-KO mouse line. Glucose metabolism and glucagon secretion in vivo was characterised; isolated islets were tested for glucagon and insulin secretion; alpha cell mass, alpha cell proliferation and α-synuclein levels were determined in pancreas sections by immunostaining.
resultsTargeted deletion of Ide exclusively in alpha cells triggers hyperglucagonaemia and alpha cell hyperplasia, resulting in elevated constitutive glucagon secretion. The hyperglucagonaemia is attributable in part to dysregulation of glucagon secretion, specifically an impaired ability of IDE-deficient alpha cells to suppress glucagon release in the presence of high glucose or insulin. IDE deficiency also leads to α-synuclein aggregation in alpha cells, which may contribute to impaired glucagon secretion via cytoskeletal dysfunction. We showed further that IDE deficiency triggers impairments in cilia formation, inducing alpha cell hyperplasia and possibly also contributing to dysregulated glucagon secretion and hyperglucagonaemia. CONCLUSIONS/
interpretationWe propose that loss of IDE function in alpha cells contributes to hyperglucagonaemia in type 2 diabetes.
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