Glucagon‐like peptides activate hepatic gluconeogenesis

Abstract

Piscine (anglerfish, catfish, coho salmon) glucagon-like peptides (GLPs), applied at 3.5 nM, stimulate (1.1-1.9-fold) flux through gluconeogenesis above control levels in isolated trout and salmon hepatocytes. Human GLP-1 and GLP-2 also activate gluconeogenesis, but to a lesser degree than their piscine counterparts. Minor increases of substrate oxidation are noticed at times of peak gluconeogenic activation through GLPs. These hormones, which are derived from the same precursor peptide as glucagon are more potent activators of gluconeogenesis than glucagon when applied at equimolar concentrations, and do not appear to employ cAMP or cGMP as the intraceilular messenger in hepatic tissue.

Absence of insulinotropic glucagon‐like peptide‐I(7–37) receptors on isolated rat liver hepatocytes

“…GLP-l(7-37) at 10 =a M has been shown to maximally stimulate cAMP formation in B.cells [7,9]; higher concentratiol~ of the peptide result in less cAMP generation due to a homologous desensitization of the B-cell receptor [9]. The data presented in this study clearly show that GLP-I(7-37) does not stimulate, in the rat, hepatic glycogenolysis (measured by phosphorylase activation) or glueoneogenesis (measured by the conversion of [=4C]lactate to [t~C]$1ucose), GLP-i(7-37) also does not increase the intracellular second messengers cAMP and Ca =" in rat liver, These data are not consistent with those ['ound in fish where GLP-I functions as a metabolic hormone [27] and activates hepatic gluconeogenesis [13]. These discrepancies in observa.…”

“…In fish hepatocytes GLPs stimulate gluconeogenesis, but they do not employ cAMP as an intracellular messenger [13], In rat liver the larger amino terminally-extended peptide GLP-I (1-371 does not alter glucagon-mediated production of cAMP [14] nor does it stimulate insulin release at all [1] or only weakly [15]. Because the short …”

Metabolic and endocrine functions of glucagon-like peptides — evolutionary and biochemical perspectives

“…Second, should the C-terminal amino acids be important in receptor binding in fish systems, as was postulated for mammalian tGLP-1, it is crucial to analyze GLP/receptor interactions in homologous systems. Our own research with hepatocytes from various species suggests the first alternative, since catfish, anglerfish, and salmon GLPs (as well as tGLP-ls), although differing substantially in their C-terminal amino acid sequences, are freely interchangeable and similarly effective in activating glycogenolysis as well as gluconeogenesis in fish hepatocytes (Mommsen et al 1987; Mommsen and Moon…”

Glucagon‐like peptide‐1(7–36) amide is a new incretin/enterogastrone candidate

“…Mammalian proglucagon exhibits several pairs of dibasic amino acid residues which are potential processing sites for enzymes [8]. In the A-cell of the pancreas proglucagon is predominantly processed into proglucagon( 1-30) (also called glicentin-related pancreatic peptide (GRPP) [9]), proglucagon which is identical with glucagon, the hexapeptide proglucagon (64)(65)(66)(67)(68)(69) [ 101 and the carboxy-terminal fragment proglucagon (72-l58) [ 1 I]. The carboxyterminal fragment contains the sequences of glucagonlike peptide-I and glucagon-like peptide-2 but is not further processed in the pancreas [I 13 (Fig.…”