Regulation of glucagon receptor expression

Nishimura, Erica; Abrahamsen, Niels; Hansen, Lone; Lundgren, Karsten; Madsen, Ole

doi:10.1046/j.1365-201x.1996.35258000.x

Cited by 13 publications

(10 citation statements)

References 6 publications

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“…Desensitization of receptors by chronic stimulation is frequently observed, as it has been reported for the glucagon receptor in glucagonoma carrying rats [48]. Thus, it is of interest that chronic administration of GLP‐1 both in vivo and in vitro may not lead to desensitization.…”

Section: Discussionmentioning

confidence: 90%

Foetal proglucagon processing in relation to adult appetite control: lessons from a transplantable rat glucagonoma with severe anorexia

Jensen

Larsen

Karlsen

et al. 2011

Diabetes Obesity Metabolism

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We have previously reported severe anorexia abruptly induced in rats 2-3 weeks after they have been transplanted subcutaneously with the glucagonoma MSL-G-AN. Vagotomy did not affect the time of onset and severity of anorexia, and the anorectic state resembles hunger with strongly elevated neuropeptide Y (NPY) mRNA levels in the nucleus arcuatus. We now show that circulating levels of bioactive glucagon-like peptide-1 (GLP-1) (7-36amide) start to increase above control levels exactly at the time of onset of anorexia. At this time-point, bioactive glucagon as well as total glucagon precursors and GLP-1 metabolites are already vastly elevated compared to controls. We further show that intravenous administration of very high concentrations of GLP-1 to hungry schedule-fed rats causes anorexia in a dose-dependent manner, which is blocked by the GLP-1 receptor antagonist exendin (9-39). GLP-1 (7-36amide) has a well-characterized anorectic effect but also causes taste aversion when administered centrally. The anorectic effect is blocked in rats treated neonatally by monosodium glutamate (MSG). We show that MSG treatment does not prevent the MSL-G-AN-induced anorexia, thereby suggesting a different type of anorectic function. We show a very strong component of taste aversion as anorectic rats, when presented to novel or known alternative food items, will resume normal feeding for 1 day, and then redevelop anorexia. We hypothetize that the anorexia in MSL-G-AN tumour-bearing rats correlates with a foetal processing pattern of proglucagon to both glucagon and GLP-1 (7-36amide), and is due to taste aversion. The sudden onset is characterized by a dramatic increase in circulating levels of biologically active GLP-1 (7-36amide), suggesting eventual saturation of proteolytic inactivation of its N-terminus.

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Section: Discussionmentioning

confidence: 90%

Foetal proglucagon processing in relation to adult appetite control: lessons from a transplantable rat glucagonoma with severe anorexia

Jensen

Larsen

Karlsen

et al. 2011

Diabetes Obesity Metabolism

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“…In rats bearing glucagon-secreting tumors, liver GR mRNA level is decreased, suggesting a negative, pretranslational effect of circulating glucagon on the expression of the GR gene [110]. Other in vivo regulators of the expression of the GR gene include thyroid status, which modulates GR mRNA level differentially in liver, brown adipose tissue and white adipose tissue [111], and cold exposure, which downregulates GR mRNA level in brown adipose tissue in a sympathetic nervous system-dependent manner [112].…”

Section: Regulation Of Expression Of the Gr In Target Cellsmentioning

confidence: 96%

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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“…The expression of the glucagon receptor gene (Gcgr) in islet cells and hepatocytes increases in response to a rise in ambient glucose (297). Conversely, exposure to chronically elevated glucagon levels decreases expression.…”

Section: B Tissue Distribution Of the Glucagon Receptormentioning

confidence: 99%

Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease

Sandoval

D’Alessio

2015

Physiological Reviews

380

345

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The preproglucagon gene (Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set of neurons within the nucleus of the solitary tract. Gcg encodes multiple peptides including glucagon, glucagon-like peptide-1, glucagon-like peptide-2, oxyntomodulin, and glicentin. Of these, glucagon and GLP-1 have received the most attention because of important roles in glucose metabolism, involvement in diabetes and other disorders, and application to therapeutics. The generally accepted model is that GLP-1 improves glucose homeostasis indirectly via stimulation of nutrient-induced insulin release and by reducing glucagon secretion. Yet the body of literature surrounding GLP-1 physiology reveals an incompletely understood and complex system that includes peripheral and central GLP-1 actions to regulate energy and glucose homeostasis. On the other hand, glucagon is established principally as a counterregulatory hormone, increasing in response to physiological challenges that threaten adequate blood glucose levels and driving glucose production to restore euglycemia. However, there also exists a potential role for glucagon in regulating energy expenditure that has recently been suggested in pharmacological studies. It is also becoming apparent that there is cross-talk between the proglucagon derived-peptides, e.g., GLP-1 inhibits glucagon secretion, and some additive or synergistic pharmacological interaction between GLP-1 and glucagon, e.g., dual glucagon/GLP-1 agonists cause more weight loss than single agonists. In this review, we discuss the physiological functions of both glucagon and GLP-1 by comparing and contrasting how these peptides function, variably in concert and opposition, to regulate glucose and energy homeostasis.

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Regulation of glucagon receptor expression

Cited by 13 publications

References 6 publications

Foetal proglucagon processing in relation to adult appetite control: lessons from a transplantable rat glucagonoma with severe anorexia

Foetal proglucagon processing in relation to adult appetite control: lessons from a transplantable rat glucagonoma with severe anorexia

Glucagon receptors

Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease

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