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

Abstract

Psammomys obesus (a desert gerbil, nicknamed the "sand rat") with innate insulin resistance was transferred to a high-energy (HE) diet at a young (8 to 20 weeks) and older (38 to 45 weeks) age. The young Psammomys progressed to in vivo insulin resistance, followed by pronounced hyperglycemia and hyperinsulinemia, 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 to normal together with insulin in the older Psammomys. Implants releasing insulin 2 IU/24 h did not induce appreciable hypoglycemia, a decrease in free fatty acids (FFAs), or a suppression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity in young animals after 5 hours, despite a markedly increased circulating insulin. However, in the older Psammomys, the exogenous hyperinsulinemia produced a significant decline in serum glucose and FFA and a suppression of hepatic PEPCK activity. A euglycemic-hyperinsulinemic 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 x min(-1) x kg(-1) v 10.9 +/- 0.8 to 3.9 +/- 0.5 mg x min(-1) x kg(-1)). This indicates that HGP, rather than glucose underutilization, was the main contributor to the hyperglycemia and that the hepatic insulin resistance in Psammomys is attenuated with age. In relation 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 pattern of diabetes prevalence that tapers off with age. As such, the nutritionally induced diabetes in Psammomys represents a similar model for a differing pattern of the age-related prevalence of diabetes.