title: Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use.
abstract: 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.
authors.affiliation: Metabolic diseases unit, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.|Department of Biomedical Sciences, Faculty of Medicine, Édouard-Montpetit, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: Taleb
authors.affiliation: Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montréal, Québec, Canada.|Division of Endocrinology, Department of Medicine, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Haidar
authors.affiliation: Metabolic diseases unit, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
authors.forename: Virginie
authors.initials: V
authors.lastname: Messier
authors.affiliation: Metabolic diseases unit, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.|Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gingras
authors.affiliation: Montreal Children's Hospital, Department of Pediatrics, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Legault
authors.affiliation: Metabolic diseases unit, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.|Montreal Diabetes Research Center, Montréal, Québec, Canada.|Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005934:Glucagon / Q000008:administration & dosage*; D006728:Hormones / Q000008:administration & dosage*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007332:Insulin Infusion Systems; D019397:Pancreas, Artificial
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon
keywords: external artificial pancreas; glucagon; glycaemic control; hypoglycaemia; type 1 diabetes