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

Mortensen, Ole Hartvig; Dichmann, Darwin S.; Abrahamsen, Niels; Grunnet, Niels; Nishimura, Erica

doi:10.1016/j.gene.2007.01.023

Cited by 6 publications

(11 citation statements)

References 41 publications

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“…Fasting glucagon values were significantly higher after the LCD compared with the HCD, which may be caused by an increased intake of protein combined with insulin-independent reduction of the glucose during the LCD (14,15). Elevated glucagon concentrations may downregulate glucagon receptors, thus leading to decreased glucagon sensitivity (16). Although this remains speculative, it could contribute to the attenuated glycemic response to glucagon observed in this study.…”

Section: Discussionmentioning

confidence: 76%

Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study

et al. 2016

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Section: Discussionmentioning

confidence: 76%

Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study

et al. 2016

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“…The most proximal exon, separated from the first coding exon by an intron of 3.2 kb, is spliced out in liver and less frequently in heart [41]. However, in the mouse [42] and human [43,44] genes, only a single untranslated exon located 4 kb upstream from the first coding exon has been identified. Furthermore, a single promoter region, located upstream from the most distal untranslated exon, has been defined in the rat GR gene [41], whereas both a proximal and a distal promoter, located upstream from the first coding exon and from the single untranslated exon, respectively, have been described in the mouse [45] and human [44] genes.…”

Section: Solubilization and Physical Characterization Of The Gr Proteinmentioning

confidence: 99%

“…However, in the mouse [42] and human [43,44] genes, only a single untranslated exon located 4 kb upstream from the first coding exon has been identified. Furthermore, a single promoter region, located upstream from the most distal untranslated exon, has been defined in the rat GR gene [41], whereas both a proximal and a distal promoter, located upstream from the first coding exon and from the single untranslated exon, respectively, have been described in the mouse [45] and human [44] genes. Structurally, these promoters lack consensus TATA and CAAT boxes, are GC rich and contain several putative Sp1 binding sites, as many promoters of housekeeping genes [46].…”

Section: Solubilization and Physical Characterization Of The Gr Proteinmentioning

confidence: 99%

“…Structurally, these promoters lack consensus TATA and CAAT boxes, are GC rich and contain several putative Sp1 binding sites, as many promoters of housekeeping genes [46]. Other interesting features include, in the rat promoter (between -545 and -527), a glucose response element consisting of a highly palindromic sequence of 19 nucleotides, centered on two E boxes (CACGTG and CAGCTG) separated by three nucleotides [41]; and in the proximal human promoter (between -1062 and -354), several CRE, C/EBPa and AP-1 elements, known to be involved in cAMP regulation of gene expression [44]. In situ hybridization to metaphase chromosome preparations have mapped the human GR gene to chromosome 17q25 [40], but the chromosomal localization of the gene in other species has not been determined.…”

Section: Solubilization and Physical Characterization Of The Gr Proteinmentioning

confidence: 99%

“…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]. In these studies, peroxisome proliferatoractivated receptor g coactivator 1a was also found to abolish cAMP-induced down-regulation of GR mRNA.…”

Section: Regulation Of Expression Of the Gr In Target Cellsmentioning

confidence: 99%

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Glucagon receptors

Authier

Desbuquois

2008

Cell. Mol. Life Sci.

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Glucagon is a pancreatic peptide hormone that, as a counterregulatory hormone for insulin, stimulates glucose release by the liver and maintains glucose homeostasis. First described as a glucagon binding entity functionally linked to adenylyl cyclase, the glucagon receptor is a member of the family B receptors within the G protein coupled superfamily of seven transmembrane-spanning receptors. During the past decade, considerable progress has been made in the identification of the molecular determinants of the glucagon receptor that are important for ligand binding and signal transduction, in the development of glucagon analogs and of nonpeptide small molecules acting as receptor antagonists, and in the characterization of the mechanisms involved in the regulation of expression of the glucagon receptor gene. In the present review, the current knowledge of glucagon receptor structure, function and expression is described, with emphasis on the metabolic fate of glucagon and on the endocytosis and cell itinerary of both ligand and receptor.

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Glucagon for hypoglycaemia treatment in type 1 diabetes

Ranjan

Schmidt

Nørgaard

2020

Diabetes Metabolism Res

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To achieve strict glycaemic control and avoid chronic diabetes complications, individuals with type 1 diabetes (T1D) are recommended to follow an intensive insulin regimen. However, the risk and fear of hypoglycaemia often prevent individuals from achieving the treatment goals. Apart from early insulin suspension in insulin pump users, carbohydrate ingestion is the only option for preventing and treating non‐severe hypoglycaemic events. These rescue treatments may give extra calories and cause overweight. As an alternative, the use of low‐dose glucagon to counter hypoglycaemia has been proposed as a tool to raise glucose concentrations without adding extra calories. Previously, the commercially available glucagon formulations required reconstitution from powder to a solution before being injected subcutaneously or intramuscularly—making it practical only for treating severe hypoglycaemia. Several companies have developed more stable formulations that do not require the time‐consuming reconstitution process before use. As well as treating severe hypoglycaemia, non‐severe and impending hypoglycaemia can also be treated with lower doses of glucagon. Once available, low‐dose glucagon can be either delivered manually, as an injection, or automatically, by an infusion pump. This review focuses on the role and perspectives of using glucagon to treat and prevent hypoglycaemia in T1D.

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

Cited by 6 publications

References 41 publications

Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study

Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study

Glucagon receptors

Glucagon for hypoglycaemia treatment in type 1 diabetes

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