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 g lucose uptake into individual tissues in Psammomys obesus. The animals were classified according to the level of circulating glucose and ins ulin in the fed state: group A was normoglycaemic and normoinsulinaemi c (glucose <8.0 mmol/l, insulin <150 mU/l), group B was normoglycaemic and hyperinsulinaemic (glucose <8.0 mmol/l, insulin greater than or e qual to 150 mU/l), and group C was hyperglycaemic and hyperinsulinaemi c (glucose greater than or equal to 8.0 mmol/l, insulin greater than o r equal to 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 gl ucose turnover was measured using a primed-continuous infusion of 6-[H -3]-glucose and saline to quantitatively assess hepatic glucose produc tion (HGP), glucose disposal (Rd), and the metabolic clearance rate of glucose (MCR). Following the 2-h infusion period, the glucose metabol ic index (Rg') of individual tissues was measured using a fixed-dose b olus of 2-deoxy-[C-14]glucose. Under the steady-state conditions of th e experiment, HGP was assumed to be equal to Rd, and both variables we re found to be significantly correlated to the fasting glucose concent ration (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 animal was significantly elevated c ompared 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 M CR were not significantly different between groups A and B. Measuremen t of the glucose metabolic index in individual tissues showed that gro up C animals had significantly higher Rg' values in muscles and adipos e 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. Thes e findings suggest that an early increase in skeletal muscle glucose u ptake and hyperinsulinaemia can be demonstrated in group B Psammomysob esus before significant hyperglycaemia.