Tremblay A.J.,Center Hospitalier Of Luniversite Laval Chul Research Center |
Tremblay A.J.,Laval University |
Lamarche B.,Laval University |
Kelly I.,Proteomic Center |
And 5 more authors.
Diabetes, Obesity and Metabolism | Year: 2014
Aim: To investigate the effects of sitagliptin therapy on the kinetics of triglyceride-rich lipoprotein (TRL) apolipoprotein (apo)B-48, VLDL apoB-100, apoE and apoC-III in patients with type 2 diabetes. Methods: Twenty-two subjects with type 2 diabetes were recruited in this double-blind crossover study, during which the subjects received sitagliptin (100 mg/day) or placebo for a 6-week period each. At the end of each phase of treatment, the in vivo kinetics of the different apolipoproteins were assessed using a primed-constant infusion of l-[5,5,5-D3]leucine for 12 h, with the participants in a constantly fed state. Results: Sitagliptin therapy significantly reduced fasting plasma triglyceride (-15.4%, p = 0.03), apoB-48 (-16.3%, p = 0.03) and free fatty acid concentrations (-9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% ± 0.8 vs. sitagliptin: 6.6% ± 0.7, p < 0.0001) and plasma glucose levels (-13.5%, p = 0.001), without any significant effect on insulin levels. Kinetic results showed that treatment with sitagliptin significantly reduced the pool size of TRL apoB-48 by -20.8% (p = 0.03), paralleled by a reduction in the production rate of these particles (-16.0%, p = 0.03). The VLDL apoB-100 pool size was also significantly decreased by sitagliptin therapy (-9.3%, p = 0.03), mainly because of a reduction in the hepatic secretion of these lipoproteins, although this difference did not reach statistical significance (-9.2%, p = 0.06). Conclusions: Treatment with sitagliptin for 6 weeks reduced triglyceride-rich apoB-containing lipoprotein levels by reducing the synthesis of these particles. © 2014 John Wiley & Sons Ltd.
Couture P.,Institute of Nutrition and Functional Foods |
Couture P.,Proteomic Center |
Tremblay A.J.,Institute of Nutrition and Functional Foods |
Tremblay A.J.,Proteomic Center |
And 4 more authors.
Journal of Lipid Research | Year: 2014
Insulin resistance (IR) is associated with elevated plasma levels of triglyceride-rich lipoproteins (TRLs) of intestinal origin. However, the mechanisms underlying the overaccumulation of apolipoprotein (apo)B-48-containing TRLs in individuals with IR are not yet fully understood. This study examined the relationships between apoB-48- containing TRL kinetics and the expression of key intestinal genes and proteins involved in lipid/lipoprotein metabolism in 14 obese nondiabetic men with IR compared with 10 insulin-sensitive (IS) men matched for waist circumference. The in vivo kinetics of TRL apoB-48 were assessed using a primed-constant infusion of L-[5,5,5-D 3 ]leucine for 12 h with the participants in a constantly fed state. The expression of key intestinal genes and proteins involved in lipid/ lipoprotein metabolism was assessed by performing realtime PCR quantifi cation and LC-MS/MS on duodenal biopsy specimens. The TRL apoB-48 pool size and production rate were 102% ( P < 0.0001) and 87% ( P = 0.01) greater, respectively, in the men with IR versus the IS men. On the other hand, intestinal mRNA levels of sterol regulatory element binding factor-2, hepatocyte nuclear factor-4 - , and microsomal triglyceride transfer protein were signifi cantly lower in the men with IR than in the IS men. These data indicate that IR is associated with intestinal overproduction of lipoproteins and signifi cant downregulation of key intestinal genes involved in lipid/lipoprotein metabolism. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.