Defective Insulin Secretory Response to Glucose in the New Zealand Obese Mouse: Improvement with Restricted Diet

Insulin and glucose tolerance tests, and tests of the plasma insulin response to injected glucose were compared in C57B ad libitum fed mice (control strain), NZO ad libitum fed mice, C57B mice with obesity due to induced hyperphagia following gold thioglucose administration, and NZO mice whose weight had been reduced to that of the control strain by dietary restriction. The ad libitum fed NZO mice showed impaired glucose tolerance, increased insulin resistance, basal hyperinsulinemia arid absent rise in plasma insulin in response to glucose injection. The gold thioglucose-treated mice also showed impaired glucose tolerance and insulin resistance, but they demonstrated a rise in plasma insulin in response to glucose injection. The NZO mice whose diet had been restricted showed variable glucose tolerance, improved but not normal insulin sensitivity, and a significant rise in plasma insulin in response to injected glucose. It is concluded that thepancreatic islets of obese NZO mice, although very responsive to arginine, are insensitive to glucose, and with- weight reduction sensitivity to glucose returns.