β-Cell function and islet morphology in normal, obese, and obese β-cell mass-reduced Göttingen minipigs

Herein, we bridge β-cell function and morphology in minipigs. We hypothesized that different aspects of β-cell dysfunction are present in obesity and obesity with reduced β-cell mass by using pulsatile insulinsecretion as an early marker. Measures for β-cell function (glucose and argininestimulation plus baseline and glucose-entrained pulsatile insulinsecretion) and islet morphology were studied in long-term (19–20 mo) obese (n = 5) and obese β-cell-reduced [nicotinamide + streptozotocin (STZ), n = 5] minipigs and normal controls, representing different stages in the development toward type 2 diabetes. Acute insulin response (AIR) to glucose and argininewere, surprisingly, normal in obese (0.3 g/kg glucose: AIR = 246 ± 119 vs. 255 ± 61 pM in control; 67 mg/kg arginine: AIR = 230 ± 124 vs. 214 ± 85 pM in control) but reduced in obese-STZ animals (0.3 g/kg glucose: AIR = 22 ± 36, P < 0.01; arginine: AIR = 87 ± 92 pM, P < 0.05 vs. control). Baseline pulsatile insulinsecretion was reduced in obese (59 ± ...