title: Effect of the new imidazoline derivative S-22068 (PMS 847) on insulin secretion in vitro and glucose turnover in vivo in rats.
abstract: We have investigated the possible mechanisms underlying the antihyperglycaemic effect of the imidazoline derivative S-22068. In vitro, in the presence of 5 mmol/l glucose, S-22068 (100 micromol/l) induced a significant and sustained increase in insulin secretion from isolated, perifused, rat islets and a marked sensitization to a subsequent glucose challenge (10 mmol/l). S-22068 (100 micromol/l was able to antagonize the stimulatory effect of diazoxide on 86Rb efflux from preloaded islets incubated in the presence of 20 mmol/l glucose. Experiments were also performed to investigate whether S-22068 can alter glucose turnover and peripheral insulin sensitivity in vivo in mildly diabetic rats and obese, insulin resistant, Zucker rats. Neither glucose production nor individual tissue glucose utilization was modified by S-22068 in either group of rats. Similar results were obtained whether the studies were performed under basal conditions or during euglycaemic/hyperinsulinemic clamps. The results suggest that S-22068 exerts part of its antihyperglycaemic effect by promoting insulin secretion without alteration of peripheral insulin sensitivity.
authors.affiliation: Laboratoire de Physiopathologie de la Nutrition, Groupe Endocrinologie Métabolique, ESA 7059, Université Paris 7-Denis Diderot, France.
authors.forename: A
authors.initials: A
authors.lastname: Pelé-Tounian
authors.forename: S L
authors.initials: SL
authors.lastname: Chan
authors.forename: F
authors.initials: F
authors.lastname: Rondu
authors.forename: G
authors.initials: G
authors.lastname: Le Bihan
authors.forename: M H
authors.initials: MH
authors.lastname: Giroix
authors.forename: A
authors.initials: A
authors.lastname: Lamouri
authors.forename: E
authors.initials: E
authors.lastname: Touboul
authors.forename: B
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: D
authors.initials: D
authors.lastname: Manechez
authors.forename: P
authors.initials: P
authors.lastname: Renard
authors.forename: B
authors.initials: B
authors.lastname: Guardiola-Lemaître
authors.forename: J J
authors.initials: JJ
authors.lastname: Godfroid
authors.forename: L
authors.initials: L
authors.lastname: Pénicaud
authors.forename: N G
authors.initials: NG
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Ktorza
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D007093:Imidazoles; D007328:Insulin; D010879:Piperazines; D012414:Rubidium Radioisotopes; C116061:S 22068; D005947:Glucose; D003981:Diazoxide