title: Sulphonylurea effects on insulin secretion in islets desensitized to glucose.
abstract: Prolonged, continuous exposure of the islets of Langerhans to high glucose concentrations results in desensitization of the beta cell to glucose stimulation. This study tested the ability of a sulphonylurea to stimulate insulin secretion in this setting. Normal isolated rat islets were cultured for 18-20 h in RPMI-1640 with 300 mg/dl glucose to induce desensitization or with 100 mg/dl as a control. Islets were then placed into a perifusion system and perifused with 60 mg/dl glucose followed by a stimulus. After preincubation at 300 mg/dl, a significant 50% suppression of glucose-induced insulin secretion compared with secretion in the control group preincubated at 100 mg/dl glucose was observed (p less than 0.025-0.001). This confirmed the occurrence of desensitization to glucose in this in vitro model. In contrast, stimulation of insulin secretion by glyburide (500 ng/ml) was unaffected compared with control. We also tested whether glyburide corrects the defective response to glucose stimulation in glucose-desensitized islets. Control islets (preincubated at 100 mg/dl) were stimulated with 300 mg/dl glucose or with this glucose concentration plus glyburide. Peak incremental insulin responses were similar (0.81 +/- 0.07 and 0.77 +/- 0.12 microU/ml.islet). After preincubation at 300 mg/dl, perifusion with 300 mg/dl glucose alone or with glyburide was associated with smaller, but similar, peak insulin responses (0.53 +/- 0.13 and 0.62 +/- 0.06 microU/ml.islet). In conclusion, islets in which the insulin-secretory response is compromised by desensitization to glucose are nevertheless completely responsive to the direct stimulatory effects of a sulphonylurea. However, the sulphonylurea does not correct the defect in glucose-induced insulin secretion.
authors.affiliation: Department of Medicine, Harbor-UCLA Medical Center, Torrance 90509.
authors.forename: D B
authors.initials: DB
authors.lastname: Zhou
authors.forename: E
authors.initials: E
authors.lastname: Ipp
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004361:Drug Tolerance; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007328:Insulin; D005947:Glucose; D005905:Glyburide