Insulin regulation of glucokinase gene expression: evidence against a role for sterol regulatory element binding protein 1 in primary hepatocytes.

Liver key genes for carbohydrate and lipid homeostasis are regulated by insulin and glucose. The sterol regulatory-element binding protein-1c (SREBP-1c) has emerged as a mediator of insulin effects on gene transcription, particularly on glucokinase (GK). In this paper, we show that despite stimulation of GK promoter transcription by overexpression of mature SREBP-1c, insulin induced GK transcription at least 4h ahead of accumulation of mature SREBP-1c in the nucleus.

In vivo functional characterization of the aldolase B gene enhancer.

A 400-bp intronic enhancer fragment in conjunction with the proximal promoter of the aldolase B gene provided correct tissue-specific expression in transgenic mice together with hormonal regulation in the liver. We investigated in vivo and in cultured cells the contribution of the intronic regulatory sequences and their interaction with the promoter elements in controlling aldolase B gene expression. Transgene activity was completely abolished by disruption of the two hepatocyte nuclear factor 1 (HNF1) binding sites in the enhancer, whereas mutation of one HNF1 site had no effect in the liver but strongly decreased activity in the kidney.