Abstract

Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was also increased in sera from pre-diabetic rats and this promoted β-cell death. Lowering apoCIII with an oligonucleotide antisense during a phase of the pre-diabetic period prolonged the time to onset of T1D. In order to find other ways to lower apoCIII we in this study tested non-alcoholic red wine with medium and high concentrations of polyphenols and the lipid-lowering drug, fenofibrate, both reported to decrease the expression of apoCIII by activating peroxisome proliferator-activated receptors. Pre-diabetic BB-rats were treated orally for one month prior to the expected onset of diabetes with the two different wines or fenofibrate. None of the treatments prevented or prolonged the time to onset of diabetes and the expression of apoCIII was unaffected in this animal model for T1D. However, it must be emphasized that this does not exclude that other species can show a response to these substances.

Highlights

  • Serum levels of the pro-inflammatory apolipoprotein CIII are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII

  • We have previously shown that lowering apoCIII by antisense treatment during the prediabetic phase prolongs the time to onset of disease [3]

  • In this study we wanted to examine whether red wine containing polyphenols or the lipid-lowering drug, fenofibrate, both reported to decrease apoCIII, have any effect on the debut of diabetes

Read more

Summary

Introduction

Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was increased in sera from pre-diabetic rats and this promoted β-cell death. Increased levels of apolipoprotein CIII (apoCIII) in sera from patients with type-1 diabetes mellitus (T1D) have been shown to promote Ca2+-induced β-cell apoptosis [1]. We have decreased the endogenous levels of apoCIII by antisense treatment between the age of 12 to 40 days, when they are still in the pre-diabetic phase, and that significantly prolonged the time to onset of diabetes [3].

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call