title: Protective effects of epoxypukalide on pancreatic β-cells and glucose metabolism in STZ-induced diabetic mice.
abstract: Diabetes is a consequence of a decrease on functional β-cell mass. We have recently demonstrated that epoxypukalide (Epoxy) is a natural compound with beneficial effects on primary cultures of rat islets. In this study, we extend our previous investigations to test the hypothesis that Epoxy protects β-cells and improves glucose metabolism in STZ-induced diabetic mice. We used 3-months old male mice that were treated with Epoxy at 200 μg/kg body weight. Glucose intolerance was induced by multiple intraperitoneal low-doses of streptozotocin (STZ) on 5 consecutive days. Glucose homeostasis was evaluated measuring plasma insulin levels and glucose tolerance. Histomorphometry was used to quantify the number of pancreatic β-cells per islet. β-cell proliferation was assessed by BrdU incorporation, and apoptosis by TUNEL staining. Epoxy treatment significantly improved glucose tolerance and plasma insulin levels. These metabolic changes were associated with increased β-cell numbers, as a result of a two-fold increase in β-cell proliferation and a 50% decrease in β-cell death. Our results demonstrate that Epoxy improves whole-body glucose homeostasis by preventing pancreatic β-cell death due to STZ-induced toxicity in STZ-treated mice.
authors.affiliation: a Instituto de Genética y Biología Molecular (University of Valladolid-CSIC) ; Valladolid , Spain.|f These authors contributed equally to this work.
authors.forename: Jose F
authors.initials: JF
authors.lastname: López-Acosta
authors.affiliation: a Instituto de Genética y Biología Molecular (University of Valladolid-CSIC) ; Valladolid , Spain.|f These authors contributed equally to this work.
authors.forename: Pablo
authors.initials: P
authors.lastname: Villa-Pérez
authors.affiliation: a Instituto de Genética y Biología Molecular (University of Valladolid-CSIC) ; Valladolid , Spain.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Fernández-Díaz
authors.affiliation: b Svo Endocrinología y Nutrición HCUVA; Centro de Investigación de Endocrinología y Nutrición (University of Valladolid); Valladolid , Spain.
authors.forename: Daniel de Luis
authors.initials: Dde L
authors.lastname: Román
authors.affiliation: c Departamento de Química Orgánica ; Instituto Universitario de Bioorgánica "Antonio González" -CIBICAN; University of La Laguna; San Cristóbal de La Laguna , Spain.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Díaz-Marrero
authors.affiliation: d Instituto de Productos Naturales y Agrobiología (CSIC) ; La Laguna , Tenerife , Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Cueto
authors.affiliation: e Facultad de Ciencias Ambientales y Bioquimica ; University of Castilla-La Mancha ; Toledo , Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Perdomo
authors.affiliation: a Instituto de Genética y Biología Molecular (University of Valladolid-CSIC) ; Valladolid , Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Cózar-Castellano
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051379:Mice
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D007783:Lactones; C044995:11,12-epoxypukalide; D005947:Glucose
keywords: diabetes; epoxypukalide; hypoglycaemic agent; pancreatic β-cells