title: The effect of G-CSF and AMD3100 on mice treated with streptozotocin: Expansion of alpha-cells and partial islet protection.
abstract: Administration of streptozotocin (STZ) is one of the most used experimental models of diabetes (STZ-DT). STZ induces beta-cell damage in pancreatic islets. It is known that hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow to damaged tissues. In this work, we evaluated the effects of the hematopoietic mobilizers G-CSF (250μg/kg; for five consecutive days) and AMD3100 (5mg/kg; single s.c injection) in mice treated with STZ (175mg/kg). Mice injected with STZ showed a significant reduction in the number and area of islets and in the number of beta- and alpha-cells. Concurrently, they had hyperglycemia (blood glucose over 300mg/dl) associated with very low levels of insulin in plasma. The number and area of islets from STZ-DT mice treated with G-CSF and/or AMD3100 were similar to the controls. However, these mice had neither a reduction of hyperglycemia nor an improvement in the insulin levels. Analysis of islet cellularity showed a large reduction in beta-cells with a significant expansion of alpha-cells. These results indicate that G-CSF and AMD3100 induce partial protection of islet tissues and expansion of alpha-cells in mice treated with STZ but do not protect beta-cells from the damage induced by this compound.
authors.affiliation: Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela; Facultad de Ciencias, Universidad Central de Venezuela, Caracas 1080, Venezuela.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Gomez
authors.affiliation: Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela.
authors.forename: Dylana
authors.initials: D
authors.lastname: Diaz-Solano
authors.affiliation: Servicio de Anatomopatología, Hospital José María Vargas, Caracas 1080, Venezuela.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gledhill
authors.affiliation: Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela.
authors.forename: Olga
authors.initials: O
authors.lastname: Wittig
authors.affiliation: Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela. Electronic address: jcardier@ivic.gob.ve.
authors.forename: Jose
authors.initials: J
authors.lastname: Cardier
mesh_terms: D000818:Animals; D001596:Benzylamines; D001786:Blood Glucose; D000080027:Cyclams; D003921:Diabetes Mellitus, Experimental; D050416:Glucagon-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006943:Hyperglycemia / Q000209:etiology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D051379:Mice; D013311:Streptozocin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001596:Benzylamines; D001786:Blood Glucose; D000080027:Cyclams; D006571:Heterocyclic Compounds; D007328:Insulin; D016179:Granulocyte Colony-Stimulating Factor; D013311:Streptozocin; C088327:plerixafor
keywords: AMD3100; Alpha-cells; Beta-cells; Diabetes; G-CSF; Streptozotocin