Measurements of insulin responses as predictive markers of pancreatic β-cell mass in normal and β-cell-reduced lean and obese Göttingen minipigs in vivo

At present, the best available estimators of β-cell mass in humans are those based on measurement of insulin levels or appearance rates in the circulation. In several animal models, these estimators have been validated against β-cell mass in lean animals. However, as many diabetic humans are obese, a correlation between in vivo tests and β-cell mass must be evaluated over a range of body weights to include different levels of insulin sensitivity. For this purpose, obese (n = 10) and lean (n = 25) Gottingen minipigs were studied. β-Cell mass had been reduced (n = 16 lean, n = 5 obese) with a combination of nicotinamide (67 mg/kg) and streptozotocin (125 mg/kg), acute insulin response (AIR) to intravenous glucose and/or arginine was tested, pulsatile insulin secretion was evaluated by deconvolution (n = 30), and β-cell mass was determined histologically. AIR to 0.3 (r2 = 0.4502, P < 0.0001) or 0.6 g/kg glucose (r2 = 0.6806, P < 0.0001), 67 mg/kg arginine (r2 = 0.5730, P < 0.001), and maximum insulin concent...