Abstract
Miniglucagon, or glucagon-[19-29], is partially processed from glucagon in its target tissues where it modulates the glucagon action. In the islets of Langerhans, the glucagon-producing A cells contain miniglucagon at a significant level (2-5% of the glucagon content). We studied a possible control of insulin release by miniglucagon using as a model the MIN6 cell line. Miniglucagon, in the 10(-14) to 10(-9) M range, inhibited insulin release induced by glucose, glucagon, tGLP-1, or glibenclamide by 85-100% with an IC50 close to 1 pM. While no change in the cyclic AMP content was noted, Ca2+ influx was reduced in parallel with the inhibition of insulin release. Use of pharmacological modulators of L-type voltage-sensitive Ca2+ channels and bacterial toxins indicates that miniglucagon blocks insulin release by closing this type of channel via a pertussis toxin-sensitive G protein. Miniglucagon is a novel, possibly physiologically relevant, local regulator of islet function.
MeSH terms
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
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Animals
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Calcium / metabolism*
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Calcium Channels / drug effects
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Calcium Channels / physiology
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Calcium Channels, L-Type
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / physiology
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Glucagon / pharmacology*
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Glucagon / physiology
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Glucagon-Like Peptide 1
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Glucagon-Like Peptides
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Glucose / pharmacology
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Glyburide / pharmacology
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Homeostasis
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Insulin / metabolism*
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Insulin Secretion
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Islets of Langerhans / drug effects
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Islets of Langerhans / metabolism
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Islets of Langerhans / physiology*
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Kinetics
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Peptide Fragments / pharmacology*
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Peptide Fragments / physiology
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Peptides / pharmacology
Substances
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Calcium Channels
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Calcium Channels, L-Type
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Insulin
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Peptide Fragments
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Peptides
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Glucagon-Like Peptides
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glucagon (19-29)
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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Glucagon-Like Peptide 1
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Glucagon
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Glucose
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glucagon-like peptide 1 (7-37)
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Glyburide
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Calcium