Basal glucose turnover in Psammomys obesus. An animal model of type 2 (non-insulin-dependent) diabetes mellitus.

The aim of this study was to examine whole-body glucose turnover and glucose uptake into individual tissues in Psammomys obesus. The animals were classified according to the level of circulating glucose and insulin in the fed state: group A was normoglycaemic and normoinsulinaemic (glucose < 8.0 mmol/l), insulin < 150 mU/l), group B was normoglycaemic and hyperinsulinaemic (glucose < 8.0 mmol/l, insulin > or = 150 mU/l), and group C was hyperglycaemic and hyperinsulinaemic (glucose > or = 8.0 mmol/l, insulin 150 mU/l). The animals were deprived of food for 6 h, after which they were anaesthetized and cannulated, using the jugular vein for infusions and the carotid artery for blood sampling. Whole-body glucose turnover was measured using a primed-continuous infusion of 6-[3H]-glucose and saline to quantitatively assess hepatic glucose production (HGP), glucose disposal (Rd), and the metabolic clearance rate of glucose (MCR). Following the 2-h infusion period, the glucose metabolic index (Rg') of individual tissues was measured using a fixed-dose bolus of 2-deoxy-[14C] glucose. Under the steady-state conditions of the experiment, HGP was assumed to be equal to Rd, and both variables were found to be significantly correlated to the fasting glucose concentration (r=0.534, P<0.05, n=19). On the other hand, MCR was found to be inversely correlated to the fasting plasma glucose concentration (r=0.670 P < 0.01, n=19). When the animals were divided into three groups as described above, HGP in group C animals was significantly elevated compared with group A (20.8 +/- 2.6 vs 12.7 +/- 0.6 mg.kg-1.min-1; P < 0.05), and MCR showed a tendency to be lower in group C than group A, although the difference was not statistically significant. HGP and MCR were not significantly different between groups A and B. Measurement of the glucose metabolic index in individual tissues showed that group C animals had significantly higher Rg' values in muscles and adipose tissues compared with those in group A (P < 0.05). In addition, Rg' in group B white gastrocnemius and soleus were significantly higher than in group A despite similar rates of HGP and levels of glycaemia. These findings suggest that an early increase in skeletal muscle glucose uptake and hyperinsulinaemia can be demonstrated in group B Psammomysobesus before significant hyperglycaemia.