The Effect of Glucagon on the Metabolic Rate of Rats

Davidson, I. W. F.; Salter, James; Best, C. H.

doi:10.1093/ajcn/8.5.540

Cited by 61 publications

(36 citation statements)

References 8 publications

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“…However, in vivo, propranolol, a nonspecific ␤-adrenergic receptor antagonist (85), blocks the effect of glucagon on BAT thermogenesis, suggesting an important indirect role mediated through the adrenergic nervous system as well. Coadministration of glucagon and epinephrine additively stimulate energy expenditure, yet the effect of glucagon is still present in adrenalectomized rats (77), dissociating glucagon action from epinephrine levels per se. One speculation is that glucagon interacts with the SNS at other tissues (e.g., the CNS).…”

Section: B Glucagonmentioning

confidence: 99%

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

Sandoval

D’Alessio

2015

Physiological Reviews

376

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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Section: B Glucagonmentioning

confidence: 99%

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

Sandoval

D’Alessio

2015

Physiological Reviews

376

345

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“…Early studies by Davidson et al . 88,89 showed that pharmacological infusion of glucagon increased oxygen consumption in rats. This effect was mirrored by a report in human study participants, in whom infusion of a pharmacological dose of glucagon increased resting energy expenditure during acute insulin deficiency produced by the additional infusion of somatostatin.…”

Section: Beyond Glucose Homeostasismentioning

confidence: 99%

The metabolic actions of glucagon revisited

et al. 2010

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The initial identification of glucagon as a counter-regulatory hormone to insulin revealed this hormone to be of largely singular physiological and pharmacological purpose. Glucagon agonism, however, has also been shown to exert effects on lipid metabolism, energy balance, body adipose tissue mass and food intake. The ability of glucagon to stimulate energy expenditure, along with its hypolipidemic and satiating effects, in particular, make this hormone an attractive pharmaceutical agent for the treatment of dyslipidemia and obesity. Studies that describe novel preclinical applications of glucagon, alone and in concert with glucagon-like peptide 1 agonism, have revealed potential benefits of glucagon agonism in the treatment of the metabolic syndrome. Collectively, these observations challenge us to thoroughly investigate the physiology and therapeutic potential of insulin's long-known opponent.

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“…The physiological role of glucagon as a glucoregulatory hormone has overshadowed evidence that it may contribute to energy homeostasis. Its ability to increase metabolic rate was described in the 1960s ; however, this pathway has not been well studied, in all likelihood because of fears that the hyperglycaemic effects of glucagon would be detrimental and outweigh improvements in metabolism. The effects of glucagon on metabolism have been comprehensively reviewed elsewhere , although it is clear that activation of the GCGR promotes increased energy expenditure, making it highly likely that the actions of OXM at this receptor are not trivial.…”

Section: Ways To Boost the Actions Of Glp‐1r: Glucagon And Co‐agonistsmentioning

confidence: 99%

Glucagon‐Like Peptide‐1 Receptor in the Brain: Role in Neuroendocrine Control of Energy Metabolism and Treatment Target for Obesity

Lockie

2013

J Neuroendocrinology

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The central glucagon-like peptide (GLP)-1 receptor mediates a number of metabolic processes, including feeding, body weight and glucose homeostasis. More recently, roles in energy expenditure and reward pathway modulation have been described. GLP-1 receptor agonism promotes insulin release and is currently used to treat type 2 diabetes humans, with a common side effect being weight loss. It is likely that many of these metabolic effects are mediated by GLP-1Rs located in the central nervous system, throughout areas known to be important in control of energy homeostasis. The physiological role of the GLP-1 receptor signalling in each of these brain nuclei is becoming clearer and the GLP-1 system appears to act as an integrator of peripheral energy availability and effector of metabolic regulation. This makes it an attractive target for obesity therapies, with excellent pre-clinical efficacy seen in molecules combining GLP-1 receptor agonism with glucagon receptor agonism. This review discusses what is known about the functions of the GLP-1 receptor in the central nervous system, and highlights the ways that this system may be targeted for development of new obesity therapeutics.

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The Effect of Glucagon on the Metabolic Rate of Rats

Cited by 61 publications

References 8 publications

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

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

The metabolic actions of glucagon revisited

Glucagon‐Like Peptide‐1 Receptor in the Brain: Role in Neuroendocrine Control of Energy Metabolism and Treatment Target for Obesity

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