Effects of a Carob-Pod-Derived Sweetener on Glucose Metabolism

Abstract

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.

Supplementation with a Carob (Ceratonia siliqua L.) Fruit Extract Attenuates the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice

“…An important finding is that supplementation with CSAT+ ® decreases the glycemic status and the HOMA-IR, suggesting improved insulin sensitivity. These results are in agreement with previous studies that report increased insulin sensitivity in response to carob treatment both in experimental animals [20] and in humans [18,19,46]. However, other authors have reported that carob consumption in combination with a glucose load increases plasma glucose and serum insulin responses in humans [47].…”

“…Among them the fruit of carob tree, (Ceratonia siliqua L.), may be a good candidate since several studies have reported that it exerts beneficial effects improving the glycemic status [18][19][20][21], the lipid profile [22][23][24][25][26], and attenuating the cardiovascular alterations associated with MetS [23,27,28]. Its therapeutic effects are attributed to several bioactive compounds that are present not only in the pulp but also in the pod and the seeds of the carob fruit.…”

The Healing-Promoting Properties of Selected Cyclitols—A Review

“…Lambert et al [37] evaluated the effect of having a drink containing natural DP from carob pods compared to a sucrose-enriched drink with a glycaemia profile in healthy volunteers, insulin resistance sufferers and type 2 diabetes. Six weeks of taking of DP-enriched beverage resulted in increased production of proteins involved in the insulin secretion pathway only in people with insulin resistance, not in healthy ones [37]. When assessing carbohydrate metabolism in rats, they proposed a new mechanism to improve this metabolism by administering DP.…”

“…It causes an increase in the amount of complement protein C4A after having a large amount of glucose, correlating with the concentration of C-peptide, which indicates increased secretion of insulin. In addition, C4A protein has a protective effect on β cells of pancreatic islets [37,56].…”

High Sugar-Fat Diet Induces Metabolic-Inflammatory Disorders Independent of Obesity Development

“…The association between obesity and the development of diseases due to the adipose tissue dysfunction is well characterized [16] [17] [18] [19]. However, since the rates of chronic diseases are increasing also in non-obese individuals [20] [21], to clarify the direct effect of nutrients on these illnesses will allow future interventions. The aim of this study was to evaluate the impact of high sugar-fat diet in the development of metabolic-inflammatory disorders in non-obese animals.…”