Gut glucagon-like immunoreactants (GLIs) and other enteric glucagon-like peptides.

Abstract

The term glucagon was coined by Kimball and an immunoreactant in common with glucagon (gut Murlin (1923) to describe a hyperglycaemic subGLIs). The extensive similarities between the stance which they had partially purified from an sequences of glucagon, VIP, secretin, and GIP have extract of bovine pancreas. In 1953, Staub et al. been discussed elsewhere in these proceedings. The crystallised a pancreatic hyperglycaemic glycofour peptides have very similar spectra of biological genolytic factor (HGF), for which they accepted the effects: secretin, glucagon, and VIP stimulate name glucagon in 1955 (Staub et al., 1955). The lipolysis, VIP and glucagon activate glycogenolysis, amino-acid sequence of porcine glucagon was and all of the peptides are insulin-releasing in one published in 1956 by Bromer et al. With the excepsystem or another (see Marks and Turner, 1977 for tion of guinea pig glucagon, all mammalian glua review). These effects are probably all exerted via cagons so far isolated have the same 29 amino-acid stimulation of adenyl cyclase but involve binding of sequence as porcine glucagon (Sundby, 1976). the peptides to separate receptors on the cell surface. Avian glucagons differ from porcine glucagon; for The physiology of secretin, VIP, and GIP is described example turkey glucagon differs by having a serine elsewhere in these proceedings so the remainder of residue at position 28 instead of asparagine, and this section is restricted to the gut glucagon-like duck glucagon by also having a threonine at position immunoreactants (gut GLIs). 16 instead of serine (Fig. 1). In the mammals studied so far, glucagon has been located mainly in the Gut glucagon-like immunoreactants pancreas, where it is synthesised in the A cells of the islets of Langerhans (Bussolati et al., 1971). A well The term gut glucagon-like immunoreactant is used characterised gastric glucagon has, however, been for any gut peptide which reacts with an antilocated in A-like cells in the canine gastric mucosa glucagon serum to prevent the binding of radio(Vranic et al., 1976). iodinated glucagon to the antibodies in the serum. The first description of a substance in the gastroThe existence of gut GLIs and the pattern of their intestinal tract with glucagon-like activities was secretion by the intestine was shown in the 1960s, the demonstration by Sutherland and de Duve largely by Unger and co-workers (1968). They react (1948) of a hyperglycaemic-glycogenolytic factor in with only one type of anti-glucagon serum, variously the canine upper gastrointestinal tract. This presentaknown as non-specific, cross-reacting, or N terminal tion summarises our knowledge of those glucagonspecific (see immunochemistry below). like peptides which have been isolated from enteric Long-chain triglycerides and glucose have been tissues since this first report. shown to release gut GLIs, as has the ingestion of Enteric peptides can be considered to be glucagonmixed meals (see Bloom and Polak, 1977 for a like if (1) they have chemical similarities to glucagon review). Plasma levels of gut GLI after an oral load (secretin, VIP, GIP, and gut GLIs); (2) they exert are above normal in subjects in whom the absorption biological effects similar to those of glucagon of focdstuffs by the upper small intestine is reduced, (secretin, VIP, GIP, and gut GLIs); or (3) they have either by malabsorption such as is found in coeliac