Intestinal microsomal triglyceride transfer protein in type 2 diabetic and non-diabetic subjects: the relationship to triglyceride-rich postprandial lipoprotein composition.
BACKGROUND
Microsomal triglyceride transfer protein (MTP) is responsible for the assembly of the triglyceride-rich lipoproteins (TRLs) and is increased in diabetic animal models. Human intestinal MTP expression has not been previously reported. This study examined the relationship between intestinal MTP gene expression and postprandial TRL composition in diabetic and non-diabetic subjects. Since the MTP promoter region has a sterol response element the effect of statins on intestinal MTP mRNA was analysed.


METHODS
Twenty-seven diabetic and 24 non-diabetic subjects were examined. Duodenal biopsies were taken during gastroscopy and MTP mRNA was measured by RNase protection assay. Postprandial lipoprotein composition was determined.


RESULTS
Diabetic subjects had significantly higher MTP mRNA than non-diabetic subjects. Statin therapy was associated with lower MTP mRNA in both groups. In the untreated diabetic patients compared to the untreated non-diabetic patients MTP mRNA was 25.0 +/- 25.1 amol/microg versus 13.1 +/- 5.6 amol/microg total RNA (p < 0.05). In the statin-treated diabetic group compared to statin-treated non-diabetic group MTP mRNA was 17.7 +/- 8.6 amol/microg versus 5.8 +/- 4.1 amol/microg total RNA (p < 0.05). In the whole group there was a positive correlation between the MTP mRNA and postprandial chylomicron cholesterol/B48 (r = 0.36, p < 0.01).


CONCLUSIONS
This is the first study to demonstrate increased MTP expression in diabetic subjects. MTP mRNA expression was lower in statin-treated patients confirming the suggestion that the insulin and sterol response elements of the MTP gene are important regulators of MTP transcription in diabetes. Our results show that MTP plays a central role in regulating the cholesterol content of the chylomicron particle.
Phillips
Catherine
C
Department of Diabetes and Endocrinology, Trinity College Dublin and The Adelaide and Meath Hospital, Diabetes Research Foundation, Clontra, Shankill, Dublin, Ireland.
Mullan
Karen
K
Owens
Daphne
D
Tomkin
Gerald H
GH
D001706:Biopsy; D002352:Carrier Proteins / Q000096:biosynthesis*; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D002352:Carrier Proteins; D002914:Chylomicrons; D008074:Lipoproteins; D012333:RNA, Messenger; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol; D012260:Ribonucleases