ArticleThe Journal of clinical investigation2014
Autophagy defends pancreatic β cells from human islet amyloid polypeptide-induced toxicity.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 2 of them syntheses that pooled it.
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Inter-organ communication shapes human metabolic tissue states and resolves anti-diabetic drug response modes in a six-tissue microphysiological system.bioRxiv : the preprint server for biology · 2026Article
- Structural and morphological dynamics of "on-path" and "off-path" oligomers of human islet amyloid polypeptide.Protein science : a publication of the Protein Society · 2026Article
- A review of autophagy in the pancreas: normal physiology and pathophysiology.Autophagy reports · 2026Review
- The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders.Metabolism open · 2025Review
- Amylin exacerbates tau pathology in the visual cortex of diabetic mice by impairing lysosomal activity.Genes & diseases · 2025Article
- Bridging Pancreatic Amyloidosis and Neurodegeneration: The Emerging Role of Amylin in Diabetic Dementia.International journal of molecular sciences · 2025Review
- Role of Autophagy in Type 2 Diabetes Mellitus: The Metabolic Clash.Journal of cellular and molecular medicine · 2024Review
- Review
- The overexpression of human amylin in pancreatic β cells facilitate the appearance of amylin aggregates in the kidney contributing to diabetic nephropathy.Scientific reports · 2024Article
- Myocardial infarction elevates endoplasmic reticulum stress and protein aggregation in heart as well as brain.Molecular and cellular biochemistry · 2024Article
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 2024Review
- PRKAA2, MTOR, and TFEB in the regulation of lysosomal damage response and autophagy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.Nature communications · 2024Article
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models.Nature communications · 2023Article
- Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.World journal of gastrointestinal surgery · 2023Article
- Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of β-cell function and glucose metabolism in subjects without diabetes.American journal of physiology. Endocrinology and metabolism · 2023Article
74 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Type 2 diabetes (T2D) is characterized by a deficiency in β cell mass, increased β cell apoptosis, and extracellular accumulation of islet amyloid derived from islet amyloid polypeptide (IAPP), which β cells coexpress with insulin. IAPP expression is increased in the context of insulin resistance, the major risk factor for developing T2D. Human IAPP is potentially toxic, especially as membrane-permeant oligomers, which have been observed to accumulate within β cells of patients with T2D and rodents expressing human IAPP. Here, we determined that β cell IAPP content is regulated by autophagy through p62-dependent lysosomal degradation. Induction of high levels of human IAPP in mouse β cells resulted in accumulation of this amyloidogenic protein as relatively inert fibrils within cytosolic p62-positive inclusions, which temporarily averts formation of toxic oligomers. Mice hemizygous for transgenic expression of human IAPP did not develop diabetes; however, loss of β cell-specific autophagy in these animals induced diabetes, which was attributable to accumulation of toxic human IAPP oligomers and loss of β cell mass. In human IAPP-expressing mice that lack β cell autophagy, increased oxidative damage and loss of an antioxidant-protective pathway appeared to contribute to increased β cell apoptosis. These findings indicate that autophagy/lysosomal degradation defends β cells against proteotoxicity induced by oligomerization-prone human IAPP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.