Mechanism of inhibitory effect of glucagon on gastrointestinal motility and cause of side effects of glucagon

Abstract

Glucagon is commonly used during gastrointestinal examinations for the temporary inhibition of gastroduodenal movements. Three preparations of glucagon are now clinically available: those prepared by extraction from the pancreas (GL-P), by chemical synthesis (GL-S), and by genetic recombination (GL-G). The aim of this study was examine the mechanism of the inhibitory effect of glucagon on gastrointestinal motility and the cause of its side effects by comparing three glucagon preparations. In four conscious dogs, gastrointestinal contractions were monitored by means of chronically implanted force transducers. Each glucagon preparation (GL-P [15 microg/kg], GL-S [5, 15, 45 microg/kg], GL-G [15 microg/kg]), scopolamine butylbromide (0.4 mg/ kg), or saline was administered intravenously 20 min after the termination of spontaneous phase III contractions, and blood samples were taken at 5- to 10-min intervals. Barium was administered into the stomach 10 min after the infusion of each drug. The arrival of a barium meal in the stomach immediately stimulated gastrointestinal contractions, and the barium meal was expelled into the duodenum and jejunum from the stomach. Intravenous injection of 15 microg GL-S first stimulated duodenal contractions that propagated to the jejunum, followed by strong inhibition of the barium-induced gastrointestinal contractions. This inhibitory effect of glucagon and the activity of the glucagon-induced duodenal contractions were dose-related. The inhibitory effects of GL-G and GL-S were stronger than that of GL-P. Blood glucose and plasma insulin concentrations were raised after intravenous injection of each glucagon preparation, but there was no difference among the three preparations and no dose relationship. The inhibitory effects of glucagon depend on the material purity and dose, and the inhibitory mechanism was independent of any effect on carbohydrate metabolism. Glucagon administration caused phase III-like contractions in the duodenum and jejunum, which may be responsible for the side effects of glucagon.

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

“…However, the glucocentric view of glucagon overshadows the other beneficial effects that it could serve beyond glucose management . Glucagon acts on the brain to decrease food intake (Salter, 1960;de Castro et al, 1978;Billington et al, 1991); it increases energy expenditure through stimulation of brown fat thermogenesis (Joel, 1966;Kuroshima and Yahata, 1979;Doi and Kuroshima, 1982), inhibits gastric motility (Watanabe et al, 1982;Mochiki et al, 1998;Shibata et al, 2001), decreases fat accumulation via stimulation of lipolysis and inhibition of lipid synthesis (Caren and Corbo, 1960;Salter et al, 1960;Paloyan and Harper, 1961;Amatuzio et al, 1962;De Oya et al, 1971;Eaton, 1973), can improve cardiac performance (Whitehouse and James, 1966;726 Glick et al, 1968;Laraia et al, 1968;Lucchesi, 1968;Katz et al, 1969), and stimulates autophagy (Deter and De Duve, 1967;Arstila and Trump, 1968;Guder et al, 1970;Deter, 1971). Collectively, these nonglycemic effects render glucagon an interesting candidate for pharmacological management of body weight.…”

The influence of duodenally-delivered Shakuyakukanzoto (Shao Yao Gan Cao Tang) on duodenal peristalsis during endoscopic retrograde cholangiopancreatography: a randomised controlled trial

“…Administration of an anti-cholinergic drug may, however, cause potentially serious complications, including cardiovascular events, urinary retention and ocular hypertension [4]. Glucagon may also be used to reduce peristalsis, but while it has fewer adverse effects on the cardiovascular system, it may induce hyperglycaemia [15]. Therefore, these drugs are not recommended for participants with cardiac disease, glaucoma, prostatic hyperplasia or diabetes mellitus [4, 15].…”

“…Glucagon may also be used to reduce peristalsis, but while it has fewer adverse effects on the cardiovascular system, it may induce hyperglycaemia [15]. Therefore, these drugs are not recommended for participants with cardiac disease, glaucoma, prostatic hyperplasia or diabetes mellitus [4, 15]. …”

Inhalable Sustained-Release Formulation of Glucagon: In Vitro Amyloidogenic and Inhalation Properties, and In Vivo Absorption and Bioactivity

“…Nanosphere recovery, encapsulation efficiency and drug content were calculated using Eqs. (1), (2) and (3), respectively. The GLG/ NS were dissolved in acetonitrile, to which 0.01 M HCl was added to preferentially precipitate the polymer.…”

“…Glucagon has been clinically used for premedication in barium enemas and clinical treatment of hypoglycemia (2). Recently, glucagon replacement therapy for patients with pancreatectomy has attracted attention since the lack of pancreatic hormones, including glucagon, sometimes causes hepatic dysfunctions and metabolic disorders of lipids and amino acids (3)(4)(5).…”