The contribution of renal and external mechanisms to hypokalemia induced by glucagon

Pettit, George W; Vick, Robert L.; Kastello, Michael D.

doi:10.1016/0014-2999(77)90264-3

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…Different states of potassium balance, ranging from hyper‐ to hypokalaemia, have been described with glucagon administration . During glucagon infusion, an initial rise in potassium levels, attributed to increased outflow of potassium from the liver, at least in part attributable to glycogenolysis, was seen in animal studies . A drop in potassium levels then follows as a result of intracellular flux under rising opposing insulin, an effect blunted in pancreatectomized animals.…”

Section: Glucagon Actionsmentioning

confidence: 99%

Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use

Taleb

Haidar

Messier

et al. 2016

Diabetes Obesity Metabolism

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The role of glucagon in the pathophysiology of diabetes has long been recognized, although its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that the incorporation of glucagon into artificial pancreas systems has the potential to further decrease hypoglycaemic risk and improve overall glucose control; however, the potential long-term safety and benefits also need to be investigated given the recognized systemic effects of glucagon. In the present report, we review the available animal and human data on the physiological functions of glucagon, as well as its pharmacological use, according to dosing and duration (acute and chronic). Along with its main role in hepatic glucose metabolism, glucagon affects the cardiovascular, renal, pulmonary and gastrointestinal systems. It has a potential role in weight reduction through its central satiety function and its role in increasing energy expenditure. Most of the pharmacological studies investigating the effects of glucagon have used doses exceeding 1 mg, in contrast to the mini-boluses used in the artificial pancreas. The available data are reassuring but comprehensive human studies using small but chronic glucagon doses that are close to the physiological ranges are lacking. We propose a list of variables that could be monitored during long-term trials of the artificial pancreas. Such trials should address the questions about the risk-benefit ratio of chronic glucagon use.

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Section: Glucagon Actionsmentioning

confidence: 99%

Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use

Taleb

Haidar

Messier

et al. 2016

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…This result suggests that glucagon increased urinary potassium excretion by a direct stimulation of potassium secretion and that glucagon could play a role in the regulation of potassium homeostasis. A few old studies had already explored the possible influence of glucagon on plasma-K and potassium excretion, but provided ambiguous results, possibly because of the confounding influence of plasma insulin, glucose, and amino acid concentrations (39,49,113,144), and of simultaneous changes in urine flow rate that also influence potassium handling in the CD (111,142). Actually, a possible contribution of insulin to the glucagon-induced rise in potassium excretion cannot be excluded.…”

Section: Possible Role Of the ␣-Cell And Glucagon In Potassium Homeostasismentioning

confidence: 99%

“…If glucagon is indeed involved in the regulation of potassium homeostasis by promoting urinary potassium excretion, it implies that the ␣-cell, responsible for glucagon secretion in pancreatic islets, should be sensitive to extracellular potassium concentration and should stimulate glucagon secretion in response to increases in plasma-K. Several studies 20 -40 years ago explored the hypothesis that changes in potassium concentration could stimulate glucagon secretion in several species, including humans, or in isolated perfused pancreas (39,49,52,97,113,144). They provided conflicting results.…”

Section: Possible Role Of the ␣-Cell And Glucagon In Potassium Homeostasismentioning

confidence: 99%

Glucagon actions on the kidney revisited: possible role in potassium homeostasis

Bankir

Bouby

Blondeau

et al. 2016

American Journal of Physiology-Renal Physiology

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It is now recognized that the metabolic disorders observed in diabetes are not, or not only due to the lack of insulin or insulin resistance, but also to elevated glucagon secretion. Accordingly, selective glucagon receptor antagonists are now proposed as a novel strategy for the treatment of diabetes. However, besides its metabolic actions, glucagon also influences kidney function. The glucagon receptor is expressed in the thick ascending limb, distal tubule, and collecting duct, and glucagon regulates the transepithelial transport of several solutes in these nephron segments. Moreover, it also influences solute transport in the proximal tubule, possibly by an indirect mechanism. This review summarizes the knowledge accumulated over the last 30 years about the influence of glucagon on the renal handling of electrolytes and urea. It also describes a possible novel role of glucagon in the short-term regulation of potassium homeostasis. Several original findings suggest that pancreatic α-cells may express a "potassium sensor" sensitive to changes in plasma K concentration and could respond by adapting glucagon secretion that, in turn, would regulate urinary K excretion. By their combined actions, glucagon and insulin, working in a combinatory mode, could ensure an independent regulation of both plasma glucose and plasma K concentrations. The results and hypotheses reviewed here suggest that the use of glucagon receptor antagonists for the treatment of diabetes should take into account their potential consequences on electrolyte handling by the kidney.

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Disorders of Potassium Metabolism

Bourgoignie¹,

Oster²,

Pérez³

et al. 1991

Therapy of Renal Diseases and Related Disorders

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The contribution of renal and external mechanisms to hypokalemia induced by glucagon

Cited by 4 publications

References 16 publications

Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use

Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use

Glucagon actions on the kidney revisited: possible role in potassium homeostasis

Disorders of Potassium Metabolism

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