Effect of upregulation of NeuroD in insulin-producing liver cells.

NeuroD (BETA2), a bHLH transcription factor is known to be involved in early pancreatic endocrine as well as neuronal differentiation. NeuroD is known to regulate distinct sets of molecules that are important for survival and differentiation of pancreatic cells. We assessed whether forced expression of NeuroD, can induce maturation of FAO-ins liver cells to β-like cells. To test this we stably transfected NeuroD into these cells that constitutively secrete insulin. Transfected cells showed enhanced expression of preproinsulin mRNA, elevated insulin content and cumulative insulin secretion. There was an up-regulation of expression of the genes for the transcription factor Foxa2, L-type Ca2+ channels subunit α 1C and α 1D and secretory granular protein chromogranin A. These FAO-ins-hNd cells show increased insulin secretion in response to calcium and theophylline, but not glucose. However, secretion of insulin remained constitutive rather than regulated. These studies demonstrate that NeuroD alone may not be sufficient to induce regulated insulin release in insulin-producing liver cells.