Disease relevance of Miniglucagon

• Pretreatment with pertussis toxin abolished the effects of miniglucagon on insulin release [1].
• In Zajdela hepatoma cells (ZHC) the plasma membrane Ca2+ pump displayed no sensitivity to glucagon (19-29) (mini-glucagon), whereas in hepatocyte this metabolite of glucagon evoked a biphasic regulation of the Ca2+ pump system via a cholera toxin-sensitive G protein [2].
• None of the peptides significantly affected refractive error in eyes with unrestricted vision, although changes in anterior and posterior eye growth were observed in response to glucagon, oxyntomodulin, GLP-1, and miniglucagon [3].
• This bypass allows miniglucagon to act as an insulin-like component, a characteristic which makes this peptide of particular interest from a pathophysiological and pharmacological point of views in understanding and treating metabolic diseases, such as the type 2 diabetes [4].

High impact information on Miniglucagon

• These results indicate that glucagon(19-29), obtained by proteolytic cleavage of glucagon, is likely to be the active peptide involved in the inhibition of the liver Ca2+ pump [5].
• It has been recently shown that the physiological processing of glucagon into its C-terminal (19-29) fragment, miniglucagon, by cardiac cells was essential for the contractile positive inotropic effect of the hormone [6].
• In the present study, we assessed the effects of miniglucagon on Ca2+ homeostasis in embryonic chick ventricular myocytes [6].
• Using confocal and electron microscopy analysis, we observed that miniglucagon is colocalized with glucagon in mature secretory granules of alpha-cells [7].
• Miniglucagon (glucagon 19-29): a novel regulator of the pancreatic islet physiology [7].

Anatomical context of Miniglucagon

• We concluded that miniglucagon is a novel local regulator of the pancreatic islet physiology and that any abnormal inhibitory tone exerted by this peptide on the beta-cell would result in an impaired insulin secretion, as observed in type 2 diabetes [7].
• Using the rat isolated-perfused pancreas, we investigated the inhibitory effect of miniglucagon on insulin secretion and evaluated the existence of an inhibitory tone exerted by this peptide inside the islet [7].
• Endopeptidase from rat liver membranes, which generates miniglucagon from glucagon [8].
• Immunoreactivity was found in liver, pancreas, and heart, which are glucagon and miniglucagon target tissues, and in gastric mucosa and kidney [8].
• Using the MIN6 B-cell line, we investigated the hypothesis that miniglucagon, the C-terminal () fragment processed from glucagon and present in pancreatic A cells, modulates insulin release, and we analyzed its cellular mode of action [1].

Associations of Miniglucagon with other chemical compounds

• The increase in 45Ca2+ uptake induced by depolarizing agents (glucose or extracellular K+), by glucagon, or by the Ca2+channel agonist Bay K-8644 was blocked by miniglucagon at the doses active on insulin release [1].
• We show that, at concentrations ranging from 0.01 to 1000 pM, miniglucagon dose-dependently (ID50 = 1 pM) inhibited by 80-100% the insulin release triggered by glucose, glucagon, glucagon-like peptide-1-(7-36) amide (tGLP-1), or glibenclamide, but not that induced by carbachol [1].
• Bacitracin inhibited this processing of glucagon into miniglucagon [9].

Gene context of Miniglucagon

• Miniglucagon (MG)-generating endopeptidase, which processes glucagon into MG, is composed of N-arginine dibasic convertase and aminopeptidase B [10].
• Glucagon-like peptide 1 (7-36) amide and glucagon (19-29) (10(-10)-10(-7) M) were without effect [11].
• It is concluded that miniglucagon is a highly potent and efficient inhibitor of insulin release by closing, via hyperpolarization, voltage-dependent Ca2+ channels linked to a pathway involving a pertussis toxin-sensitive G protein [1].
• Miniglucagon (MG), the C-terminal glucagon fragment, processed from glucagon by the MG-generating endopeptidase (MGE) at the Arg17-Arg18 dibasic site, displays biological effects opposite to that of the mother-hormone [10].
• In purified endosomal fractions, miniglucagon endopeptidase was undetectable as evaluated by immunoblotting, and immunoprecipitation with antibodies to insulin-degrading enzyme, cathepsins B and D, or furin failed to remove the endosomal neutral glucagonase activity [12].

Analytical, diagnostic and therapeutic context of Miniglucagon

• Incubation of glucagon with heart cells led to its rapid conversion into miniglucagon, as measured by radioimmunoassay [9].
• These results demonstrate a useful and convenient method to assay gene therapy products circulating in blood using a glucagon 19-29 tagging vector [13].

References