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unige:34529 
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The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation |
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| Published in | Cell Metabolism. 2005, vol. 2, no. 6, p. 373-84 | |
| Abstract | Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis. | |
| Keywords | Animals — Base Sequence — Blotting, Northern — Calcium/metabolism — Cell Line — Cloning, Molecular — DNA, Complementary/metabolism — Diabetes Mellitus, Type 2/metabolism — Disease Models, Animal — Exocytosis — Genes, Reporter — Glucose/chemistry/metabolism — Glutathione Transferase/metabolism — Growth Hormone/metabolism — Hepatocyte Nuclear Factor 1/metabolism — Humans — Immunoblotting — Immunohistochemistry — Immunoprecipitation — Insulin/metabolism/secretion — Insulin-Secreting Cells/metabolism — Insulinoma — Islets of Langerhans/cytology — Membrane Glycoproteins/metabolism — Mice — Mice, Transgenic — Microscopy, Fluorescence — Microscopy, Immunoelectron — Models, Genetic — Molecular Sequence Data — Nucleic Acid Hybridization — Oligonucleotide Array Sequence Analysis — Pancreas/metabolism — Photons — Protein Binding — RNA, Messenger/metabolism — RNA, Small Interfering/metabolism — Rats — Reverse Transcriptase Polymerase Chain Reaction — SNARE Proteins/metabolism — Time Factors — Tissue Distribution — Transcription, Genetic — Two-Hybrid System Techniques | |
| Identifiers | PMID: 16330323 | |
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| Citation (ISO format) | FUKUI, Kenji et al. The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. In: Cell Metabolism, 2005, vol. 2, n° 6, p. 373-84. https://archive-ouverte.unige.ch/unige:34529 |
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