Linogliride fumarate, an oral hypoglycemic agent, improves oral glucose tolerance in a rat model of non‐insulin‐dependent diabetes mellitus (NIDDM)

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Abstract
Linogliride fumarate, a structurally novel oral hypoglycemic compound, was tested in the neonatal streptozotocin‐induced rat model of non‐insulin‐dependent diabetes mellitus (NIDDM) [Weir et al.: Diabetes 30:590–595, 1981], and its antihyperglycemic effects were compared to those of representative first and second generation sulfonylureas. Two‐day‐old male Sprague‐Dawley rats (STZ) were injected with the beta cell toxin, streptozotocin (90 mg/kg i.p.); male littermates injected with citrate buffer served as controls (CTL). By 8 weeks of age, blood glucose of fed STZ rats was significantly elevated compared to that of CTL animals (>300 mg/dl vs.30 = 12.5 mg/kg) was approximately six times as potent as tolbutamide (ED30 = 72.1 mg/kg) in improving oral glucose tolerance in STZ rats, while glyburide (0.5–2.5 mg/kg p.o.) and glipizide (2.5 mg/kg) were ineffective. This rat model of NIDDM may be useful for evaluating new hypoglycemic compounds.