Targeted deletion of Insm2 in mice result in reduced insulin secretion and glucose intolerance.
J Transl Med
; 16(1): 297, 2018 10 25.
Article
em En
| MEDLINE
| ID: mdl-30359270
ABSTRACT
BACKGROUND:
Neurogenin3 (Ngn3) and neurogenic differentiation 1 (NeuroD1), two crucial transcriptional factors involved in human diabetes (OMIM 601724) and islet development, have been previously found to directly target to the E-boxes of the insulinoma-associated 2 (Insm2) gene promoter, thereby activating the expression of Insm2 in insulin-secretion cells. However, little is known about the function of Insm2 in pancreatic islets and glucose metabolisms.METHODS:
Homozygous Insm2-/- mice were generated by using the CRISPR-Cas9 method. Glucose-stimulated insulin secretion and islet morphology were analyzed by ELISA and immunostainings. Expression levels of Insm2-associated molecules were measured using quantitative RT-PCR and Western blots.RESULTS:
Fasting blood glucose levels of Insm2-/- mice were higher than wild-type counterparts. Insm2-/- mice also showed reduction in glucose tolerance and insulin/C-peptide levels when compared to the wild-type mice. RT-PCR and Western blot analysis revealed that expression of Insm1 was significantly increased in Insm2-/- mice, suggesting a compensatory response of the homolog gene Insm1. Similarly, transcriptional levels of Ngn3 and NeuroD1 were also increased in Insm2-/- mice. Moreover, Insm2-/- female mice showed a significantly decreased reproductive capacity.CONCLUSIONS:
Our findings suggest that Insm2 is important in glucose-stimulated insulin secretion and is involved in the development pathway of neuroendocrine tissues which are regulated by the transcription factors Ngn3, NeuroD1 and Insm1.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Deleção de Genes
/
Intolerância à Glucose
/
Secreção de Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China