title: In vivo effects of glucose and insulin on secretion and gene expression of glucagon in rats.
abstract: We investigated the effects of insulin and glucose on the control of secretion and gene expression of glucagon in vivo in rats. Animals were studied during 1) a 48-h period of either glucose infusion (hyperglycemia plus hyperinsulinemia; HG-HI rats) or insulin infusion (euglycemia plus hyperinsulinemia; EG-HI rats), and 2) a prolonged postinfusion period in both groups. In HG-HI rats, elevation of plasma insulin and glucose concentrations by about 7 and 5 times, respectively, resulted in a decline in glucagon levels, which fell significantly within 6 h and remained low thereafter, whereas these levels were unchanged in EG-HI rats. Glucagon messenger RNA levels and pancreatic glucagon content were not significantly affected in either HG-HI or EG-HI rats. After cessation of infusions, hypoglycemia occurred in both group of rats. In HG-HI rats, hypoglycemia lasted for about 36 h without any surge in the plasma glucagon level, whereas in EG-HI rats it was transient (approximately 1 h) and stimulated glucagon secretion. In both groups the pancreatic alpha-cell was unresponsive to arginine during the postinfusion period. In conclusion, although a role of intraislet insulin cannot be excluded, glucagon gene expression is insensitive to changes in plasma glucose and insulin concentrations. In contrast, hyperglycemia/hyperinsulinemia, not hyperinsulinemia alone, lowers glucagon secretion and affects the alpha-cell responsiveness to hypoglycemia.
authors.affiliation: Laboratoire de Physiopathologie de la Nutrition, Centre National de la Recherche Scientifique URA 307, Université, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Magnan
authors.forename: J
authors.initials: J
authors.lastname: Philippe
authors.forename: N
authors.initials: N
authors.lastname: Kassis
authors.forename: M C
authors.initials: MC
authors.lastname: Laury
authors.forename: L
authors.initials: L
authors.lastname: Pénicaud
authors.forename: M
authors.initials: M
authors.lastname: Gilbert
authors.forename: A
authors.initials: A
authors.lastname: Ktorza
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D005934:Glucagon; D001120:Arginine; D005947:Glucose