Changing pattern of prevalence of insulin resistance in Psammomys obesus, a model of nutritionally induced type 2 diabetes

Psammomys obesus (a desert gerbil, nicknamed the "sand rat") with innate in sulin resistance was transferred to a high-energy (HE) diet at a young (8 t o 20 weeks) and older (38 to 45 weeks) age. The young Psammomys progressed to in vivo insulin resistance, followed by pronounced hyperglycemia and hyp erinsulinemia, as described previously. Analysis of the time dependency of these changes in response to the HE diet showed that the increase in serum glucose preceded the increase in insulin and plateaued earlier, reverting t o normal together with insulin in the older Psammomys. Implants releasing i nsulin 2 IU/24 h did not induce appreciable hypoglycemia, a decrease in fre e fatty acids (FFAs), or a suppression of hepatic phosphoenolpyruvate carbo xykinase (PEPCK) activity in young animals after 5 hours, despite a markedl y increased circulating insulin. However, in the older Psammomys, the exoge nous hyperinsulinemia produced a significant decline in serum glucose and F FA and a suppression of hepatic PEPCK activity. A euglycemic-hyperinsulinem ic clamp confirmed that hepatic glucose production (HGP) was lower in older Psammomys versus the young and was almost completely abolished by insulin (from 5.6 +/- 0.6 to 0.2 +/- 0.1 mg . min(-1) . kg(-1) v 10.9 +/- 0.8 to 3. 9 +/- 0.5 mg . min(-1) . kg(-1)). This indicates that HGP, rather than gluc ose underutilization, was the main contributor to the hyperglycemia and tha t the hepatic insulin resistance in Psammomys is attenuated with age. In re lation to the human condition, these findings point out that while the type 2 diabetes prevalence in Western populations generally increases with age, the excessive nutritional intake in high-risk populations produces a patte rn of diabetes prevalence that tapers off with age. As such, the nutritiona lly induced diabetes in Psammomys represents a similar model for a differin g pattern of the age-related prevalence of diabetes. Copyright (C) 1999 by W.B. Saunders Company.