Pancreatic hypersensitivity to glucose by young obese Zucker rats (fa/fa)

Insulin secretory response to glucose was investigated in 5- to 6-week-old male Zucker obese (fa/fa) and lean (Fa/Fa) rats using a pancreatic perfusion procedure. Blood glucose response to fasting was studied in lean and obese animals over 24 hours. Plasma glucose was slightly elevated in pentobarbital-anesthetized obese rats. However, plasma insulin was 4.6 times greater than that of leans. A hypoglycemic glucose stimulus (75 mg/dL) caused pancreata from obese animals to release 6 times more insulin than lean animals. Stimuli of 125 mg/dL (normoglycemic) and 600 mg/dL (hyperglycemic) caused hypersecretion of 8 and 5 times, respectively. Hypersecretion was not accounted for solely by the twofold increase in pancreatic insulin content. Obese animals had steeper decreases in plasma glucose than lean controls during seven to 13 hours of fasting. Hypersecretion by pancreata from young obese rats to physiological levels of glucose may result in hyperphagia in order to maintain normoglycemia.