A CROSS-SECTIONAL AND SHORT-TERM LONGITUDINAL CHARACTERIZATION OF NIDDM IN PSAMMOMYS-OBESUS

The present study was undertaken to examine the cross-sectional and short-term longitudinal changes in glucose and insulin concentrations as well as measure the enzymatic activity of PEPCK and glycogen synthase in our Psammomys obesus colony. In the cross-sectional study, blood samples were taken from one group of animals at 19 weeks of age (n = 37) in the fed state and following a 4-h fast. In a separate group of 19-week-old animals (n = 69), samples were taken 1 h following an OGTT (1 g/kg body weight) in Psammomys subjected to a 16-h fast. In the longitudinal study, blood samples were taken from one group of animals in the fed state at 7, 11, 15 and 19 weeks of age. All of the cross-sectional data have described the classic inverted U-shaped curve (Starling's curve of the pancreas) in the relationship between glucose and insulin levels. This trend was also reflected by Psammomys subjected to the OGTT; a mild impairment in glucose tolerance was associated with an increase in the insulin response and a further impairment in glucose tolerance was associated with a reduction in the insulin response. Similar results were obtained following a 4-h fast. The short-term longitudinal glucose and insulin data revealed that of the 37 animals examined over the 12-week period, 16 progressed along the inverted U-shaped curve described by the cross-sectional data. Of the other animals, 8 remained unchanged, 7 were unclassifiable and 6 hyperglycaemic Psammomys developed normoglycaemia at the expense of elevated insulin levels. Psammomys were divided into four separate groups based on their glucose and insulin levels in the fed state at age 19 weeks: group A were normoglycaemic (4.5 +/- 0.2 mmol/l) and normoinsulinaemic (81 +/- 15 mU/l); group B were normoglycaemic (5.3 +/- 0.3 mmol/l) and hyperinsulinaemic (267 +/- 19 mU/l); group C were hyperglycaemic (16.9 +/- 1.4 mmol/l) and hyperinsulinaemic (356 +/- 29 mU/l); group D were hyperglycaemic (20.4 +/- 1.4 mmol/l) and normoinsulinaemic (92 +/- 56 mU/l). Analysis of liver and soleus muscle tissue revealed that active glycogen synthase activity was reduced in the hyperglycaemic Psammomys (C and D). Total glycogen synthase activity (in liver and muscle) and PEPCK activity (in liver) were not different between groups A-D. These findings add to those already published which suggest Psammomys is an ideal animal model for the study of NIDDM.