title: No non-redundant function of suppressor of cytokine signaling 2 in insulin producing β-cells.
abstract: The members of the Suppressor of Cytokine Signaling (SOCS) protein family mainly modulate the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. SOCS-1 and SOCS-3 have already been shown to influence growth and apoptosis of pancreatic beta cells. We hypothesized that SOCS-2, which is expressed in pancreatic islets, also contributes to β-cell physiology. We tested this hypothesis in vivo in SOCS-2-/- knockout mice and in vitro in Ins-1E rat insulinoma cells. We found that SOCS-2-/- mice have normal islet insulin secretion and unchanged glucose and insulin tolerance compared to wildtype controls. SOCS-2-/- are bigger than wildtype mice but body weight-corrected β-cell mass and islet morphology were normal. Growth hormone-induced proliferation of Ins-1E cells was not affected by either siRNA-mediated SOCS-2 knockdown or stable SOCS-2 overexpression. Interleukin-1β mediated cell death in vitro was unchanged after SOCS-2 knockdown. Similarly, autoimmune destruction of beta cells in vivo after multiple low-dose injections of streptozotocin (STZ) was not altered in SOCS-2-/- mice. In summary, SOCS-2-/- knockout mice have a normal function of insulin-producing pancreatic β-cells, a fully adapted beta cell mass and a normal morphology of the endocrine islets. Based on in vitro evidence, the increased β-cell mass in the mutants is likely due to indirect adaptive mechanisms and not the result of altered growth hormone signaling within the β-cells. Immune mediated β-cell destruction is also not affected by SOCS-2 ablation in vitro and in vivo.
authors.affiliation: Ludwig-Maximilians University, Munich, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Puff
authors.forename: Petra
authors.initials: P
authors.lastname: Dames
authors.forename: Michaela
authors.initials: M
authors.lastname: Weise
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Klaus
authors.initials: K
authors.lastname: Parhofer
authors.forename: Andreas
authors.initials: A
authors.lastname: Lechner
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D055785:Gene Knockdown Techniques; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013311:Streptozocin; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D001786:Blood Glucose; D034741:RNA, Small Interfering; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D013311:Streptozocin