Long-term gliclazide treatment improves the in vitro glucose-induced insulin release in rats with Type 2 (non-insulin-dependent) diabetes induced by neonatal streptozotocin
Open Access
- 1 August 1989
- journal article
- research article
- Published by Springer Nature in Diabetologia
- Vol. 32 (8) , 577-584
- https://doi.org/10.1007/bf00285331
Abstract
Neonatal rats treated with streptozotocin on the day of birth (n0-STZ) or on day 5 (n5-STZ) exhibited when fully grown a very mild or frank basal hyperglycaemia respectively and a specific failure of insulin release in response to glucose. To determine whether short (1 day) or long-term (30 days) gliclazide treatment modifies the pancreatic insulin content and the B-cell response to secretagogues, diabetic rats were given oral gliclazide (10 mg/kg per day) and compared to control diabetic and non-diabetic rats. Insulin secretion in the isolated perfused pancreas was studied the day after the last gliclazide administration. In severely hyperglycaemic n5-STZ rats (plasma glucose levels >16 mmol/l) long-term gliclazide treatment did not lower the plasma glucose values, did not affect the pancreatic insulin stores, nor did it significantly modify the insulin release in vitro in response to glucose or arginine. In moderately hyperglycaemic n5-STZ rats (plasma glucose levels <16 mmol/l) the plasma glucose levels declined progressively reaching 8 mmol/l as a mean at the end of the gliclazide therapy. In the n5-STZ rats responsive to gliclazide the pancreatic insulin stores were increased twofold as compared to values in untreated n5-STZ rats, however, this difference did not reached significance and the pancreatic in sulin stores in the responsive gliclazide treated rats remained depleted by 76% compared to normal insulin stores. In the n0-STZ rats (very mild hyperglycaemia) the long-term gliclazide treatment did not significantly modify the plasma glucose levels or the pancreatic insulin stores. After the 30-day gliclazide therapy in both the n5-STZ gliclazide responder group and the n0-STZ group: (1) the in vitro glucose-induced insulin secretion was increased three to fivefold, (2) the response to arginine which was basically increased in the untreated diabetic rats was again amplified two to threefold, (3) the insulin release in response to gliclazide was unchanged. In conclusion, long-term gliclazide therapy augments stimulated insulin secretion in these two rat models of Type 2 (non-insulin-dependent) diabetes and does not induce any refractoriness to acute sulfonylurea stimulation. The improvement of B-cell function observed here was not related to the concomitant variations of hyperglycaemia and/or pancreatic insulin contentKeywords
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