Very low density lipoprotein metabolism after insulin over-treatment and during a euglycaemic clamp

The disturbance of very low density lipoprotein (VLDL) metabolism that occurs as a result of intensive insulin treatment and during a euglycaemic clamp have been investigated in a rat model. Normal rats were maintained with fed blood glucose levels below 5 mmol l-1 for 8 weeks by subcutaneous insulin injections (normal fed levels 5.8 +/- 0.4 (SD) mmol l-1). Glucose requirement to maintain a glucose clamp was significantly reduced (116 +/- 3 mumol min-1 kg-1 (SE) vs. 173 +/- 5 mumol min-1 kg-1, P less than 0.001), compared with weight-matched normal control rats. In the fasting state (blood glucose 3.5 +/- 0.2 mmol l-1 vs. 3.9 +/- 0.1 mmol l-1, NS) plasma non-esterified fatty acid levels were reduced. Fasting VLDL-triglyceride turnover, measured by bolus injection of 14C-VLDL, was also lower (3.17 +/- 0.12 mumol min-1 kg-1 vs. 3.50 +/- 0.07 mumol min-1 kg-1, P less than 0.05). Despite decreased turnover, insulin over-treated rats had normal plasma triglyceride concentrations indicating a removal defect. At the end of a 3-h euglycaemic clamp, plasma triglyceride concentrations and VLDL-triglyceride turnover were decreased in both normal control and insulin over-treated animals, and turnover remained significantly lower in the insulin over-treated rats (2.59 +/- 0.13 mumol min-1 kg-1 vs. 3.08 +/- 0.10 mumol min-1 kg-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)