Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

Research output: Contribution to journalJournal articleResearchpeer-review

  • Natalia Gustavsson
  • Ye Lao
  • Anton Maximov
  • Jen-Chieh Chuang
  • Elena Kostromina
  • Joyce J Repa
  • Cai Li
  • George K Radda
  • Thomas C Südhof
  • Weiping Han

Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, have not been established. By analogy to the role of synaptotagmin-1, -2, and -9 in neurotransmission, these other synaptotagmins may serve as Ca(2+) transducers regulating other Ca(2+)-dependent membrane processes, such as insulin secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor controlling insulin secretion in pancreatic beta cells.

Original languageEnglish
JournalNational Academy of Sciences. Proceedings
Volume105
Issue number10
Pages (from-to)3992-7
Number of pages6
ISSN0027-8424
DOIs
Publication statusPublished - 11 Mar 2008

    Research areas

  • Adipose Tissue, Animals, Body Weight, Calcium Signaling, Female, Glucose, Glucose Intolerance, Insulin, Insulin-Secreting Cells, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, NADP, Synaptotagmins, Journal Article, Research Support, Non-U.S. Gov't

ID: 172513294