en
Scientific article
English

Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass

Published inCell metabolism, vol. 14, no. 3, p. 365-377
Publication date2011
Abstract

Decreased β cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human β cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented β cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of β cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic β cell mass.

Keywords
  • Adolescent
  • Amino Acid Sequence
  • Amyloid Precursor Protein Secretases/antagonists & inhibitors/genetics/metabolism
  • Animals
  • Aspartic Acid Endopeptidases/antagonists & inhibitors/genetics/metabolism
  • Blood Glucose/analysis
  • Cells, Cultured
  • Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism
  • Enzyme Inhibitors/pharmacology
  • Female
  • Gene Silencing/drug effects
  • Humans
  • Insulin/metabolism/pharmacology
  • Insulin Resistance
  • Insulin-Secreting Cells/cytology/drug effects/metabolism
  • Membrane Glycoproteins/antagonists & inhibitors/genetics/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Molecular Sequence Data
  • Plasmids
  • RNA, Small Interfering/pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/genetics
  • Species Specificity
  • Substrate Specificity
  • Transfection
Citation (ISO format)
ESTERHÁZY, Daria et al. Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass. In: Cell metabolism, 2011, vol. 14, n° 3, p. 365–377. doi: 10.1016/j.cmet.2011.06.018
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1550-4131
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