title: Adiponectin counteracts cytokine- and fatty acid-induced apoptosis in the pancreatic beta-cell line INS-1.
abstract: OBJECTIVE
  Pancreatic beta-cell apoptosis is a common feature of Type 1 and Type 2 diabetes and leptin exerts an anti-apoptotic function in these cells. The beta-cell line INS-1 was used to test the hypothesis that the adipocyte hormone adiponectin might mediate an anti-apoptotic effect comparable to leptin.
  
  
  METHODS
  Apoptosis was induced by culturing cells with a cytokine combination (interleukin-1beta/interferon-gamma) or palmitic acid in absence or presence of leptin or the globular domain of adiponectin (gAcrp30), respectively.
  
  
  RESULTS
  INS-1 cells had a prominent sensitivity towards cytokine- and fatty acid-induced apoptosis, resulting in about three- and six-fold increases in caspase 3 activation and DNA fragmentation, respectively. gAcrp30 strongly (50-60%) inhibited palmitic acid-induced apoptosis, with a weaker effect against cytokine-induced apoptosis (35%). The same result was observed for leptin with both adipokines being non-additive. Reduction of apoptosis by an inhibitor of IkappaB-kinase (IKK) indicated the involvement of the nuclear factor (NF)-kappaB pathway in both cytokine- and fatty acid-induced apoptosis, however, leptin and gAcrp30 were unable to block NF-kappaB activation. Cytokine- and fatty-acid-induced suppression of glucose/forskolin-stimulated insulin secretion was completely prevented through the action of gAcrp30, whereas leptin was only effective against lipotoxicity-mediated beta-cell dysfunction.
  
  
  CONCLUSIONS
  Our data show that gAcrp30 partially rescues beta cells from cytokine- and fatty-acid-induced apoptosis and completely restores autoimmune- and lipotoxicity-induced dysfunction of insulin-producing cells. We suggest that gAcrp30 exerts its anti-apoptotic function without modulating NF-kappaB activation. This novel beta cell protective function of gAcrp30 might serve to counteract autoimmune- and lipotoxicity-induced beta-cell destruction.
authors.affiliation: Department of Clinical Biochemistry and Pathobiochemistry, German Diabetes Research Institute, Düsseldorf, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Rakatzi
authors.forename: H
authors.initials: H
authors.lastname: Mueller
authors.forename: O
authors.initials: O
authors.lastname: Ritzeler
authors.forename: N
authors.initials: N
authors.lastname: Tennagels
authors.forename: J
authors.initials: J
authors.lastname: Eckel
mesh_terms: D052242:Adiponectin; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D051550:I-kappa B Kinase; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D019308:Palmitic Acid / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats
chemical_list: D052242:Adiponectin; D016207:Cytokines; D005227:Fatty Acids; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D020738:Leptin; D016328:NF-kappa B; D005576:Colforsin; D019308:Palmitic Acid; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005947:Glucose