Cell coupling regulates Ins1, Pdx-1 and MafA to promote insulin secretion in mouse pancreatic beta cells

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• 作者：Kai-Chiang Yang^a ; ^b ; ^c ; Zhi Qi^a ; ^d ; Goichi Yanai^a ; Yasumasa Shirouza^a ; Dai-Hua Lu^b ; Hsuan-Shu Lee^b ; ^e ; ^{benlee@ntu.edu.tw"" rel=""nofollow} ; Shoichiro Sumi^a ; ^{sumi@frontier.kyoto-u.ac.jp"" rel=""nofollow}
• 关键词：Beta-cell ; Glucose-stimulated insulin secretion ; Cell coupling
• 刊名：Process Biochemistry
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：46
• 期：9
• 页码：1853-1860
• 全文大小：515 K

文摘

The intracellular contact between pancreatic β-cells plays an important role in functional insulin secretion. We propose cell coupling may regulate glucose-stimulated insulin gene expression. MIN-6, a murine β-cell line, was cultured on the Lipidure-coat dish for cell clusters formation. The responses to glucose-stimulation between monolayers and clusters were compared. The coupling of β-cells was evaluated by immunohistochemical (IHC) staining. After the establishment of cell coupling was confirmed, the transcription factors of insulin gene expression were assessed by RT-PCR. Results showed that in addition to secrete insulin in a glucose-regulated manner, MIN-6 clusters had biphasic insulin secretion. Relative to monolayer, clusters have higher stimulation-index and lower constitutive insulin release. IHC staining showed the connexin 36 highly expressed in clusters. Compared with monolayers, the mRNA expression of insulin 1 (Ins1) and homeodomain transcription factor pancreatic/duodenal homebox-1 (Pdx-1) of clusters were downregulated in low glucose level. On the contrary, these gene expressions were upregulated when clusters cultured in high glucose environment. The V-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA) was relative highly expressed in clusters under high glucose condition. This study reveals that cell coupling regulates glucose-stimulated insulin gene expression to promote insulin secretion in mouse β-cells.