Intestinal microsomal triglyceride transfer protein in type 2 diabetic and non-diabetic subjects: The relationship to triglyceride-rich postprandial lipoprotein composition

• Published in: Atherosclerosis Vol. 187; no. 1; pp. 57 - 64
• Main Authors: Phillips, Catherine, Mullan, Karen, Owens, Daphne, Tomkin, Gerald H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.07.2006; Elsevier
• Subjects: Apo B100; Apo B48; Associated diseases and complications; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biopsy; Blood and lymphatic vessels; Cardiology. Vascular system; Carrier Proteins - biosynthesis; Case-Control Studies; Cholesterol - metabolism; Chylomicrons - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Gene Expression Regulation; Humans; Intestines - metabolism; Lipoproteins - chemistry; Lipoproteins - metabolism; Male; Management. Various non-drug treatments. Langerhans islet grafts; Medical sciences; Microsomal triglyceride transfer protein (MTP); Middle Aged; Postprandial Period; Ribonucleases - metabolism; RNA, Messenger - metabolism; Statins; Triglyceride-rich lipoproteins; Triglycerides - metabolism; Type 2 diabetes; apo B48; Type 2 diabetes; TRLs; Triglyceride-rich lipoproteins; Microsomal triglyceride transfer protein (MTP); VLDL; apo B100; MTP; D2; Statins; Endocrinopathy; Animal model; Pancreatic hormone; Lipids; Cardiovascular disease; Esterases; Lipoprotein; Small intestine; Vascular disease; Particle; Chylomicron; Atherosclerosis; Apo B48; Endoscopy; Human; Duodenum; Digestive system; Enzyme; Postprandial; Metabolic diseases; Statin derivative; Gastroscopy; Gene expression; Triglyceride; Insulin; Cholesterol; Treatment; Biopsy; Hydrolases; Pancreatic ribonuclease; Comparative study; Apo B100; Antilipemic agent; Sterol
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2005.08.020

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. 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. 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/μg versus 13.1 ± 5.6 amol/μg 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/μg versus 5.8 ± 4.1 amol/μg 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). 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.