title: Abnormal B-cell function in rats with non-insulin-dependent diabetes induced by neonatal streptozotocin: effect of in vivo insulin, phlorizin, or vanadate treatments.
abstract: Neonatal rats treated with streptozotocin on day 5 after birth (n5-STZ model) exhibited, when fully grown, a frank basal hyperglycemia (17.4 +/- 0.7 vs. 6.6 +/- 0.2 mmol/L in nondiabetic rats), a specific failure of glucose-induced insulin release, and hyperresponse to arginine. To investigate whether or not chronic correction of the hyperglycemia can improve the defects on insulin secretion, we tested diverse maneuvers, all of which aimed to lower chronically the hyperglycemia. Insulin secretion was studied with the isolated perfused pancreas preparation. A 16-day subcutaneous insulin therapy (approximately 10 U/kg/day) unevenly correcting the plasma glucose levels (10.8 +/- 1.6 mmol/L) did not improve the lack of insulin response to glucose while the arginine-induced insulin release returned to values close to normal. A 28-day intraperitoneal phlorizin infusion (50 mg/kg/day0 or a 20-day oral vanadate administration (40 mg/kg/day) caused near normalization of the basal plasma glucose level in the treated n5-STZ rats (7.8 +/- 0.5 and 8.2 +/- 0.5 mmol/L, respectively). Nevertheless, these treatments did not correct the insulin secretion in response to glucose nor the hyperresponsiveness to arginine. Furthermore, we investigated whether or not glucopenia in vitro could restore the glucose-induced insulin release in this diabetic model. After a 50 min glucose-free period, the insulin response to a subsequent glucose stimulation still did not materialize. These observations suggest that in the present n5-STZ diabetic model, (a) hyperresponsiveness to arginine cannot be solely regarded as a residual effect of hyperglycemia; (b) the return to normal values of insulin release in response to arginine after insulin therapy, despite a still prevailing mild hyperglycemia, suggests that exogenous insulin per se may regulate to some extent the diabetic B cells; and (c) near normalization of the basal glucose levels is not a sufficient condition to obtain improvement of the B-cell response to glucose, such a finding being consistent with the concept that stringent normalization of glycemia is a prerequisite.
authors.affiliation: Laboratoire de Physiologie du Développement, CNRS URA 160, Université Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Serradas
authors.forename: D
authors.initials: D
authors.lastname: Bailbé
authors.forename: O
authors.initials: O
authors.lastname: Blondel
authors.forename: B
authors.initials: B
authors.lastname: Portha
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010695:Phlorhizin / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014638:Vanadates; D001120:Arginine; D010695:Phlorhizin; D005947:Glucose