Your browser doesn't support javascript.
loading
Laforin and malin knockout mice have normal glucose disposal and insulin sensitivity.
DePaoli-Roach, Anna A; Segvich, Dyann M; Meyer, Catalina M; Rahimi, Yasmeen; Worby, Carolyn A; Gentry, Matthew S; Roach, Peter J.
Afiliação
  • DePaoli-Roach AA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hum Mol Genet ; 21(7): 1604-10, 2012 Apr 01.
Article em En | MEDLINE | ID: mdl-22186021
Lafora disease is a fatal, progressive myoclonus epilepsy caused in ~90% of cases by mutations in the EPM2A or EPM2B genes. Characteristic of the disease is the formation of Lafora bodies, insoluble deposits containing abnormal glycogen-like material in many tissues, including neurons, muscle, heart and liver. Because glycogen is important for glucose homeostasis, the aberrant glycogen metabolism in Lafora disease might disturb whole-body glucose handling. Indeed, Vernia et al. [Vernia, S., Heredia, M., Criado, O., Rodriguez de Cordoba, S., Garcia-Roves, P.M., Cansell, C., Denis, R., Luquet, S., Foufelle, F., Ferre, P. et al. (2011) Laforin, a dual-specificity phosphatase involved in Lafora disease, regulates insulin response and whole-body energy balance in mice. Hum. Mol. Genet., 20, 2571-2584] reported that Epm2a-/- mice had enhanced glucose disposal and insulin sensitivity, leading them to suggest that laforin, the Epm2a gene product, is involved in insulin signaling. We analyzed 3-month- and 6-7-month-old Epm2a-/- mice and observed no differences in glucose tolerance tests (GTTs) or insulin tolerance tests (ITTs) compared with wild-type mice of matched genetic background. At 3 months, Epm2b-/- mice also showed no differences in GTTs and ITTs. In the 6-7-month-old Epm2a-/- mice, there was no evidence for increased insulin stimulation of the phosphorylation of Akt, GSK-3 or S6 in skeletal muscle, liver and heart. From metabolic analyses, these animals were normal with regard to food intake, oxygen consumption, energy expenditure and respiratory exchange ratio. By dual-energy X-ray absorptiometry scan, body composition was unaltered at 3 or 6-7 months of age. Echocardiography showed no defects of cardiac function in Epm2a-/- or Epm2b-/- mice. We conclude that laforin and malin have no effect on whole-body glucose metabolism and insulin sensitivity, and that laforin is not involved in insulin signaling.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicemia / Resistência à Insulina / Ubiquitina-Proteína Ligases / Fosfatases de Especificidade Dupla Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: Hum Mol Genet Assunto da revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicemia / Resistência à Insulina / Ubiquitina-Proteína Ligases / Fosfatases de Especificidade Dupla Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: Hum Mol Genet Assunto da revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos