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

✍ Scribed by Carol S. Marchione; Robert W. Tuman

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 472 KB
• Volume: 17
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430170208

✦ Synopsis

Marchione, C.S., and R.W. Tuman: Linogliride fumarate, an oral hypoglycemic agent, improves oral glucose tolerance in a rat model of non-insulin-dependent diabetes mellitus (NIDDM). Drug Dev. Res. 17:161-168, 1989. Linogliride fumarate, a structurally novel oral hypoglycemic compound, was tested in the neonatal streptozotocininduced rat model of non-insulin-dependent diabetes mellitus (NIDDM) [Weir et al.: Diabetes 30:590-595, 19811, 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 mgfkg Lp.); 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 mgidl vs. <110 mg/dl, respectively) and, in response to an oral glucose (1 g/kg) challenge, 18 hr fasted STZ rats exhibited marked glucose intolerance. Linogliride fumarate (1 0-1 00 mgikg p.0.) significantly lowered blood glucose in 18 hr fasted STZ rats and produced a dose-dependent improvement of oral glucose tolerance. Linogliride fumarate (ED30 = 12.5 mgikg) was approximately six times as potent as tolbutamide (EDso = 72.1 rngikg) in improving oral glucose tolerance in STZ rats, while glyburide (0.5-2.5 mg/kg p.0.) and glipizide (2.5 mg/kg) were ineffective. This rat model of NIDDM may be useful for evaluating new hypoglycemic compounds.