In a previous study, the administration of a grape seed procyanidin extract (GSPE) in female Wistar rats improved insulin resistance, reduced insulin production, and modulated apoptosis biomarkers in the pancreas. Considering that pharmacokinetic and pharmacodynamic parameters in females are different from these parameters in males, the aim of the present study was to evaluate the effects of GSPE on male Wistar cafeteria-induced obese rats. The results have confirmed that the cafeteria model is a robust model mimicking a prediabetic state, as these rats display insulin resistance, increased insulin synthesis and secretion, and increased apoptosis in the pancreas. In addition, GSPE treatment (25？mg/kg of GSPE for 21 days) in male rats improves insulin resistance and counteracts the cafeteria-induced effects on insulin synthesis. However, the administration of the extract enhances the cafeteria-induced increase in Bax protein levels, suggesting increased apoptosis. This result contradicts previous results from cafeteria-fed female rats, in which GSPE seemed to counteract the increased apoptosis induced by the cafeteria diet. 1. Introduction Procyanidins are the second most abundant natural phenolic after lignin, and they are widely distributed in fruits, berries, beans, nuts, cocoa, and wine [1]. They are potent antioxidants that possess biological properties that may protect against cardiovascular diseases [1]. They participate in glucose homeostasis [2] and modulate insulin synthesis, secretion, and degradation [3]. Moreover, changes in β-cell insulin production may also be due to variations in the number of insulin-producing cells. β-cell mass adapts to increased metabolic demands caused, for example, by obesity, pregnancy, or insulin resistance. However, when β-cells are unable to compensate for increased insulin demand, there is a decrease in β-cell mass characteristic of the onset of type 2 diabetes mellitus (T2DM) [4]. Procyanidins modulate apoptotic and proliferation processes, mainly reported in cancerous cell lines [5]. Moreover, they protect cells from diverse drug- or chemical-induced toxic assaults by decreasing apoptosis and inducing cell growth [5]. However, there is little information available regarding their effects on β-cells. Other studies by our research group have reported that procyanidins modulate proliferation and apoptosis of the pancreatic β-cell line INS-1E under altered conditions [6]. Procyanidins also alter the protein and/or gene expression of factors involved in apoptosis in Zucker fatty rats [7]. Obesity has become a
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