title: Effect of insulin analogues on phosphatidyl inositol-3 kinase/Akt signalling in INS-1 rat pancreatic derived β-cells.
abstract: BACKGROUND
  Insulin analogues are largely used for the treatment of diabetic patients, but concerns have been raised about their mitogenic/anti-apoptotic potential. It is therefore important to evaluate these analogues in different cell systems.
  
  
  OBJECTIVE
  The aim of this work was to establish the pharmacological profiles of insulin analogues towards PI-3 kinase/Akt pathway in INS-1 β-pancreatic cells.
  
  
  METHODS
  Bioluminescence Resonance Energy Transfer (BRET), in cell western and caspase 3/7 assays, was used to study the effects of ligands.
  
  
  RESULTS
  Among the five analogues evaluated, only glargine stimulated PI-3 kinase/Akt pathway with higher efficiency than insulin, whereas glargine's metabolite M1 was less efficient. However, glargine did not show higher anti-apoptotic efficiency than insulin.
  
  
  CONCLUSIONS
  Glargine was more efficient than insulin for the activation of PI-3 kinase/Akt pathway, but not for the inhibition of caspase 3/7 activity. Moreover, glargine's metabolite M1 displayed lower efficiency than insulin towards PI-3 kinase/Akt activation and caspase 3/7 inhibition.
authors.affiliation: a Inserm, U1016, Institut Cochin , Paris , France .|b CNRS, UMR8104 , Paris , France .|c Université Paris Descartes, Sorbonne Paris Cité , Paris , France , and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pagesy
authors.affiliation: a Inserm, U1016, Institut Cochin , Paris , France .|b CNRS, UMR8104 , Paris , France .|c Université Paris Descartes, Sorbonne Paris Cité , Paris , France , and.
authors.forename: Yann
authors.initials: Y
authors.lastname: Fardini
authors.affiliation: a Inserm, U1016, Institut Cochin , Paris , France .|b CNRS, UMR8104 , Paris , France .|c Université Paris Descartes, Sorbonne Paris Cité , Paris , France , and.
authors.forename: Tuyet Thu
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: d Sanofi-Aventis , Frankfurt , Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lohmann
authors.affiliation: a Inserm, U1016, Institut Cochin , Paris , France .|b CNRS, UMR8104 , Paris , France .|c Université Paris Descartes, Sorbonne Paris Cité , Paris , France , and.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pierre-Eugene
authors.affiliation: d Sanofi-Aventis , Frankfurt , Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Tennagels
authors.affiliation: a Inserm, U1016, Institut Cochin , Paris , France .|b CNRS, UMR8104 , Paris , France .|c Université Paris Descartes, Sorbonne Paris Cité , Paris , France , and.
authors.forename: Tarik
authors.initials: T
authors.lastname: Issad
mesh_terms: D000818:Animals; D002460:Cell Line; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000069036:Insulin Glargine / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007328:Insulin; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate; D000069036:Insulin Glargine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: BRET; Insulin analogues; PI-3 kinase/Akt signalling; diabetes; pancreatic β-cells