ArticleDiabetologia2013
Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- The adaptor protein APPL2 controls glucose-stimulated insulin secretion via F-actin remodeling in pancreatic β-cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- APPL2 Negatively Regulates Olfactory Functions by Switching Fate Commitments of Neural Stem Cells in Adult Olfactory Bulb via Interaction with Notch1 Signaling.Neuroscience bulletin · 2020Article
- Hepatic nitric oxide synthase 1 adaptor protein regulates glucose homeostasis and hepatic insulin sensitivity in obese mice depending on its PDZ binding domain.EBioMedicine · 2019Article
- Metabolic regulation through the endosomal system.Traffic (Copenhagen, Denmark) · 2019Review
- Perilipin5 protects against lipotoxicity and alleviates endoplasmic reticulum stress in pancreatic β-cells.Nutrition & metabolism · 2019Article
- Endocrine Adiponectin-FGF15/19 Axis in Ethanol-Induced Inflammation and Alcoholic Liver Injury.Gene expression · 2018Review
- Alternative splicing variant of the scaffold protein APPL1 suppresses hepatic adiponectin signaling and function.The Journal of biological chemistry · 2018Article
- APPL1 prevents pancreatic beta cell death and inflammation by dampening NFκB activation in a mouse model of type 1 diabetes.Diabetologia · 2017Article
- Deletion of β-Arrestin2 in Mice Limited Pancreatic β-Cell Expansion under Metabolic Stress through Activation of the JNK Pathway.Molecular medicine (Cambridge, Mass.) · 2016Article
- Appl1 and Appl2 are Expendable for Mouse Development But Are Essential for HGF-Induced Akt Activation and Migration in Mouse Embryonic Fibroblasts.Journal of cellular physiology · 2016Article
- Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus.American journal of human genetics · 2015Article
- APPL1 acts as a protective factor against podocytes injury in high glucose environment.International journal of clinical and experimental pathology · 2015Article
- APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.Cell reports · 2014Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
aims/hypothesisAdaptor protein, phosphotyrosine interaction, pleckstrin homology domain and leucine zipper containing 1 (APPL1) is an adapter protein that positively mediates adiponectin signalling. Deficiency of APPL1 in the target tissues of insulin induces insulin resistance. We therefore aimed, in the present study, to determine its role in regulating pancreatic beta cell function.
methodsA hyperglycaemic clamp test was performed to determine insulin secretion in APPL1 knockout (KO) mice. Glucose- and adiponectin-induced insulin release was measured in islets from APPL1 KO mice or INS-1(832/13) cells with either APPL1 knockdown or overproduction. RT-PCR and western blotting were conducted to analyse gene expression and protein abundance. Oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential were assayed to evaluate mitochondrial function.
resultsAPPL1 is highly expressed in pancreatic islets, but its levels are decreased in mice fed a high-fat diet and db/db mice compared with controls. Deletion of the Appl1 gene leads to impairment of both the first and second phases of insulin secretion during hyperglycaemic clamp tests. In addition, glucose-stimulated insulin secretion (GSIS) is significantly decreased in islets from APPL1 KO mice. Conversely, overproduction of APPL1 leads to an increase in GSIS in beta cells. In addition, expression levels of several genes involved in insulin production, mitochondrial biogenesis and mitochondrial OCR, ATP production and mitochondrial membrane potential are reduced significantly in APPL1-knockdown beta cells. Moreover, suppression or overexproduction of APPL1 inhibits or stimulates adiponectin-potentiated GSIS in beta cells, respectively. CONCLUSIONS/
interpretationOur study demonstrates the roles of APPL1 in regulating GSIS and mitochondrial function in pancreatic beta cells, which implicates APPL1 as a therapeutic target in the treatment of type 2 diabetes.
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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.