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Miniglucagon: A Local Regulator of Islet Physiology
Author(s) -
DALLE STÉPHANE,
BLACHE PHILIPPE,
LENGUYEN DUNG,
BRIGAND LAURENCE,
BATAILLE DOMINIQUE
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb11171.x
Subject(s) - glucagon , islet , insulin , glibenclamide , pertussis toxin , regulator , chemistry , medicine , endocrinology , biology , g protein , biochemistry , receptor , diabetes mellitus , gene
A bstract : 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 IC 50 close to 1 pM. While no change in the cyclic AMP content was noted, Ca 2+ influx was reduced in parallel with the inhibition of insulin release. Use of pharmacological modulators of L‐type voltage‐sensitive Ca 2+ 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.