Lab Anim Res.  2018 Sep;34(3):126-131. 10.5625/lar.2018.34.3.126.

Neither polyphenol-rich red wine nor fenofibrate affects the onset of type-1 diabetes mellitus in the BB rat

Affiliations
  • 1The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden. Lisa.juntti-berggren@ki.se

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.

Keyword

Apolipoprotein CIII; red wine; fenofibrate; diabetes

MeSH Terms

Animals
Apolipoprotein C-III
Apoptosis
Diabetes Mellitus*
Fenofibrate*
Humans
Models, Animal
Peroxisome Proliferator-Activated Receptors
Polyphenols
Rats
Rats, Inbred BB*
Wine*
Apolipoprotein C-III
Fenofibrate
Peroxisome Proliferator-Activated Receptors
Polyphenols

Figure

  • Figure 1 Age at diabetes onset and body weight at the end of the treatments. Pre-diabetic rats were treated with water (white), non-alcohol containing red wine with medium (black) or high (grey) levels of polyphenols from 30–60 days of age. A) Age at onset of diabetes. B) Body weight at the end of the treatments. Data are presented as mean SEM (n= 9, 3 and 5, respectively).

  • Figure 2 Age at diabetes onset and body weight at the end of the treatment with fenofibrate. Pre-diabetic rats were treated with vehicle (white) or a daily dose of 100 mg/kg fenofibrate (black) from 30 to 60 days of age. A) Age at onset of diabetes. B) Body weight at the end of the treatment. Data are presented as mean SEM (n=4).

  • Figure 3 Expression of apoCIII and PPARα in liver. Expression of apoCIII after treatment with A) water (white) or wine with high content of polyphenols (black) and B) vehicle (white) or fenofibrate (black). C) Expression of PPARα after treatment with water (white) or wine with high content of polyphenols (black). Data are presented as mean SEM (n=3–4)


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