Controlling post-prandial hyperglycemia and hyperlipidemia, particularly by regulating the activity of digestive enzymes, allows managing type 2 diabetes and obesity. The aim of this study was to assess the effects of TOTUM-63, a formulation of five plant extracts (Olea europaea L., Cynara scolymus L., Chrysanthellum indicum subsp. afroamericanum B.L.Turner, Vaccinium myrtillus L., and Piper nigrum L.), on enzymes involved in carbohydrate and lipid absorption. First, in vitro inhibition assays were performed by targeting three enzymes: α-glucosidase, α-amylase, and lipase. Then, kinetic studies and binding affinity determinations by fluorescence spectrum changes and microscale thermophoresis were performed. The in vitro assays showed that TOTUM-63 inhibited all three digestive enzymes, particularly α-glucosidase (IC₅₀ of 13.1 µg/mL). Mechanistic studies on α-glucosidase inhibition by TOTUM-63 and molecular interaction experiments indicated a mixed (full) inhibition mechanism, and higher affinity for α-glucosidase than acarbose, the reference α-glucosidase inhibitor. Lastly, in vivo data using leptin receptor-deficient (db/db) mice, a model of obesity and type 2 diabetes, indicated that TOTUM-63 might prevent the increase in fasting glycemia and glycated hemoglobin (HbA1c) levels over time, compared with the untreated group. These results show that TOTUM-63 is a promising new approach for type 2 diabetes management via α-glucosidase inhibition.

In vitro experiments using rodent skeletal muscle cells suggest that neuregulin 1 (NRG1) is involved in glucose metabolism regulation, although no study has evaluated the role of NRG1 in systemic glucose homeostasis. The purpose of this study was to investigate the effect of chronic and acute NRG1 treatment on glucose homeostasis in db/db mice. To this aim, glucose tolerance tests were performed in 8-week-old male db/db mice after treatment with NRG1 (50μg.kg^-1) or saline 3 times per week for 8 weeks. In other experiments, glucose tolerance and pyruvate tolerance tests were performed in db/db mice 15 minutes after a single NRG1 (50μg.kg^-1) or saline injection. Liver, adipose tissue, hypothalamus and skeletal muscle were also collected 30 minutes after acute NRG1 (50μg.kg^-1) or saline treatment, and the phosphorylation status of the ERBB receptors, AKT (on Ser473) and FOXO1 (on Ser256) was assessed by western blotting. Chronic treatment (8 weeks) with NRG1 improved glucose tolerance in db/db mice. Acute treatment also lowered glycemia and insulinemia during glucose or pyruvate tolerance tests. NRG1 acute injection induced activation of ERBB3 receptors and phosphorylation of AKT and FOXO1 only in liver. Altogether, this study shows that acute and chronic NRG1 treatments improve glucose tolerance in db/db mice. This effect could be mediated through inhibition of hepatic gluconeogenesis.

Tennis tournaments often involve playing several consecutive matches interspersed with short periods of recovery. The objective of this study was firstly to assess the impact of several successive tennis matches on the physical performance of competitive players and secondly to evaluate the potential of sports drinks to minimize the fatigue induced by repeated matches. This was a crossover, randomized controlled study. Eight male regionally-ranked tennis players participated in this study. Players underwent a series of physical tests to assess their strength, speed, power and endurance following the completion of three tennis matches each of two hours duration played over three consecutive half-days (1.5éday period for each condition). In the first condition the players consumed a sports drink before, during and after each match; in the second, they drank an identical volume of placebo water. The results obtained were compared with the third `resté condition in which the subjects did not play any tennis. Main outcomes measured were maximal isometric strength and fatigability of knee and elbow extensors, 20-m sprint speed, jumping height, specific repeated sprint ability test and hand grip strength. The physical test results for the lower limbs showed no significant differences between the three conditions. Conversely, on the upper limbs the EMG data showed greater fatigue of the triceps brachii in the placebo condition compared to the rest condition, while the ingestion of sports drinks attenuated this fatigue. This study has demonstrated for the first time that, when tennis players are adequately hydrated and ingest balanced meals between matches, then no large drop in physical performance is observed even during consecutive competitive matches. ClinicalTrials.gov: NCT01353872.