The Role of microsomal triglyceride transfer protein and dietary cholesterol in chylomicron production in diabetes

Aims/hypothesis. The aim of this study was to examine factors involved in c hylomicron production in the streptozotocin diabetic rat, our hypothesis be ing that the synthesis of the chylomicron is abnormal in diabetes. Methods. Diabetic rats (n = 20) were paired with control rats (n = 20). Cho lesterol emulsion was given by gavage and the lymph duct was cannulated. Ly mph was collected for 4 h. Chylomicrons were prepared from the lymph by ult racentrifugation. Lymph apolipoprotein B48 was isolated by gradient gel ele ctrophoresis and quantified by densitometric scanning. Intestinal microsoma l triglycerol transfer protein mRNA was measured by solution hybridisation nuclease protection, using a rat specific [P-32]-labelled cRNA probe. Results. Serum triglyceride and cholesterol were greatly increased in diabe tic compared with control animals (258 +/- 77 and 8.9 +/- 6.3 mg/ml vs 1.04 +/- 0.37 and 0.54 +/- 0.03 mg/ml, p < 0.0001). Lymph chylomicron triglycer ide and cholesterol were also higher in diabetic rats (29.4 +/- 27.3 and 0. 28 +/- 0.3 mg/h vs 16.8 +/- 10.6 and 0.18 +/- 0.09 mg/h, p < 0.05). Lymph c hylomicron ago B48 was Similar in the two groups. Intestinal microsomal tri glycerol transfer protein mRNA was higher in the diabetic rats (12.6 +/- 3. 2 vs 3.8 +/- 3.0 amol/mu g RNA, p < 0.0001) and there was a positive correl ation between lymph triglyceride and microsomal triglycerol transfer protei n mRNA in the whole group (r = 0.65, p < 0.01). Conclusion/interpretation. The study shows that microsomal triglycerol tran sfer protein mRNA is raised in diabetes without an increase in apolipoprote in B48 in the lymph suggesting that microsomal triglycerol transfer protein regulates chylomicron triglyceride content but not particle number.