Background: Patients with type 2 diabetes mellitus (T2DM) have a higher incidence of cardiovascular (CV) events. The ingestion of high-glycemic index (GI) diets, specially sweetened beverage consumption, has been associated with the development of T2DM and CV disease. Objective: We investigated the effects of the intake of a sweetened beverage, obtained from natural carbohydrates containing pinitol (PEB) compared to a sucrose-enriched beverage (SEB) in the context of impaired glucose tolerance (IGT) and diabetes. Methods: The study was divided in three different phases: (1) a discovery phase where the plasma proteomic profile was investigated by 2-DE (two-dimensional electrophoresis) followed by mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight—MALDI-TOF/TOF) in healthy and IGT volunteers; (2) a verification phase where the potential mechanisms behind the observed protein changes were investigated in the discovery cohort and in an additional group of T2DM volunteers; and (3) the results were validated in a proof-of-concept interventional study in an animal model of diabetic rats with complementary methodologies. Results: Six weeks of pinitol-enriched beverage (PEB) intake induced a significant increase in two proteins involved in the insulin secretion pathway, insulin-like growth factor acid labile subunit (IGF1BP-ALS; 1.3-fold increase; P
= 0.200) and complement C4A (1.83-fold increase; P
= 0.007) in IGT subjects but not in healthy volunteers. Changes in C4A were also found in the serum samples of Zucker diabetic fatty (ZDF) rats after four weeks of PEB intake compared to basal levels (P
= 0.042). In addition, an increased expression of the glucose transporter-2 (GLUT2) gene was observed in the jejunum (P
= 0.003) of inositol-supplemented rats when compared to sucrose supplementation. This change was correlated with the observed change in C4A (P
= 0.002). Conclusions: Our results suggest that the substitution of a common sugar source, such as sucrose, by a naturally-based, pinitol-enriched beverage induces changes in the insulin secretion pathway that could help to reduce blood glucose levels by protecting β-cells and by stimulating the insulin secretion pathway. This mechanism of action could have a relevant role in the prevention of insulin resistance and diabetes progression.
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