title: Phenylpropenoic acid glucoside augments pancreatic beta cell mass in high-fat diet-fed mice and protects beta cells from ER stress-induced apoptosis.
abstract: METHODS
  A major goal of diabetes therapy is to identify novel drugs that preserve or expand pancreatic beta cell mass. Here, we examined the effect of a phenylpropenoic acid glucoside (PPAG) on the beta cell mass, and via which mechanism this effect is established.
  
  
  RESULTS
  Mice were fed a high-fat and fructose-containing diet to induce obesity and hyperglycemia. PPAG treatment protected obese mice from diet-induced hyperglycemia and resulted in a tripling of beta cell mass. The effect of the phytochemical on beta cell mass was neither due to increased proliferation, as determined by Ki67 immunostaining, nor to neogenesis, which was assessed by genetic lineage tracing. TUNEL staining revealed suppressed apoptosis in PPAG-treated obese mice. In vitro, PPAG protected beta cells from palmitate-induced apoptosis. It protected beta cells against ER stress by increasing expression of antiapoptotic B-cell lymphoma 2 (BCL2) protein without affecting proapoptotic signals.
  
  
  CONCLUSIONS
  We identified an antidiabetic phytochemical that protects pancreatic beta cells from ER stress and apoptosis induced by high-fat diet/lipotoxicity. At the tissue level, this led to a tripling of beta cell mass. At the molecular level, the protective effect of the phytochemical was mediated by increasing BCL2 expression in beta cells.
authors.affiliation: Cell Differentiation Lab, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Iris
authors.initials: I
authors.lastname: Mathijs
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Da Cunha
authors.forename: Eddy
authors.initials: E
authors.lastname: Himpe
authors.forename: Laurence
authors.initials: L
authors.lastname: Ladriere
authors.forename: Nireshni
authors.initials: N
authors.lastname: Chellan
authors.forename: Candice R
authors.initials: CR
authors.lastname: Roux
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joubert
authors.forename: Christo
authors.initials: C
authors.lastname: Muller
authors.forename: Miriam
authors.initials: M
authors.lastname: Cnop
authors.forename: Johan
authors.initials: J
authors.lastname: Louw
authors.forename: Luc
authors.initials: L
authors.lastname: Bouwens
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005632:Fructose / Q000009:adverse effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008082:Lipotropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications / Q000209:etiology; D010666:Phenylpropionates / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C000591224:2-(glucopyranosyloxy)-3-phenylpropenoic acid; D005960:Glucosides; D007004:Hypoglycemic Agents; D008082:Lipotropic Agents; D010666:Phenylpropionates; D019253:Proto-Oncogene Proteins c-bcl-2; D005632:Fructose
keywords: Beta cell apoptosis; Beta cell regeneration; Lipotoxicity; Type 2 diabetes