Functional analysis of the glucose response element of the rat glucagon receptor gene in insulin-producing INS-1 cells

Identification of a novel human glucagon receptor promoter: Regulation by cAMP and PGC-1α

“…3A). Portois et al have demonstrated that rat glucagon receptor promoter constructs are active in the pancreatic islet cell line, INS-1, and have also shown that transcriptional activity is increased by high glucose through two palindromic E-boxes (Portois et al, 2002). This is consistent with our previous findings that high glucose upregulates glucagon receptor mRNA expression both in cultured pancreatic islets and hepatocytes .…”

“…Both the mouse and the rat glucagon receptor promoters have been well characterized (Burcelin et al, 1995;Geiger et al, 2000Geiger et al, , 2001aPortois et al, 1999) and the glucose response of the rat promoter has also been extensively studied (Portois et al, , 2000(Portois et al, , 2002Svoboda et al, 1999) whereas the mechanism by which cAMP downregulates glucagon receptor expression has not been defined. The structure of the rat and mouse glucagon receptor genes has been found to be very similar, except that the rat gene only has one functional promoter, whereas the mouse gene has two active promoters separated by a large 3.8 kb intron (Burcelin et al, 1995;Geiger et al, 2000;Portois et al, 1999).…”

Glucagon receptors

“…Indeed, deletion or mutation of this sequence abolishes glucose regulation. In subsequent studies, only the most 5E box of the glucose response element was found to be crucial for the glucose transcriptional effect, and USF1/USF2 transcription factors were shown to be part of the DNA binding proteins involved [113]. In addition, an accessory factor binding site was identified in the DNA region just upstream from the glucose response element [113].…”

“…In subsequent studies, only the most 5E box of the glucose response element was found to be crucial for the glucose transcriptional effect, and USF1/USF2 transcription factors were shown to be part of the DNA binding proteins involved [113]. In addition, an accessory factor binding site was identified in the DNA region just upstream from the glucose response element [113]. Comparable studies, in which partial sequences of the human GR gene promoter have been fused to luciferase and expressed in HepG2 hepatoma cells, have shown that the activity of the proximal promoter, but not that of the distal promoter, is inhibited by cAMP [44].…”

Betatrophin is correlated with glucagon and insulin release rather than insulin resistance marker in type 2 diabetes mellitus Iraqi women

“…Glucagon receptor is upregulated in β-cells in response to rising concentrations of glucose. 30 This may have essential biological consequences in diabetes as fasting and postprandial glucagon levels are raised because of a loss of negative control by insulin. 31 In T2DM, hyperglucagonemia is one of the numerous factors that participate in changing β-cell function along with islet inflammation and lipotoxicity.…”