Impaired postprandial glucose handling increases the risk of developing insulin resistance in individuals with overweight or obesity. Anthocyanins have been shown to improve postprandial glucose metabolism in both human and in vitro studies; however, mechanistic insights are often derived from models using supraphysiological doses or non-physiological conditions, limiting their relevance to human physiology. Integrating ex-vivo human plasma into cell models offers a more translational approach to understanding anthocyanin bioactivity.

Purpose Explore the effect of short-term supplementation with anthocyanin-rich New Zealand blackcurrant (NZBC) extract on postprandial glucose responses to a high-carbohydrate drink and potential regulatory mechanisms in skeletal muscle.

Methods This study used a combination of in-vivo and in-vitro methods. In study 1, Fifteen overweight (BMI > 25 kg•m²) sedentary individuals participated in a double-blinded, randomised controlled trial. Participants supplemented with 0 mg, 300 mg, 600 mg, and 900 mg NZBC extract per day (CurraNZ^®) for 7-days, and glucose tolerance was assessed on day 7 (n = 15), and again on day 8 (n = 13). In study 2, GLUT4 translocation was determined in L6-GLUT4myc myotubes in vitro treated first with a supraphysiological dose (10 µg•mL^-1) of NZBC extract and subsequently with culture medium conditioned with fasting human plasma derived from participants in study 1 after 7 days of 900 mg•d⁻¹ NZBC supplementation (n = 4). L6-GLUT4myc myotubes were plasma starved for 3 h before incubation for 40 min in medium containing 10 µg•mL^-1 NZBC extract, or 2-20% fasting human plasma, after which GLUT4 translocation was determined via colorimetric assay.
Results Plasma glucose and insulin concentrations increased following high carbohydrate test drink ingestion (main effect of time, P < 0.001). No effect of NZBC dose was observed on 2hr postprandial glucose on day 7 or day 8. However, in response to short-term supplementation with 900 mg•d^-1 NZBC extract, mean insulin concentrations were significantly greater compared to placebo (NZBC: 40.6 (35.1 – 46.9) µU•mL^-1, Placebo: 28.9 (24.6 – 34.3)  µU•mL^-1, P = 0.011). Incubation with a supraphysiological dose of NZBC extract caused a time-dependent increase in cell surface GLUT4myc abundance (1.89-fold increase vs. baseline, P < 0.001). Similarly, medium conditioned with fasted human plasma from NZBC-supplemented participants increased GLUT4myc abundance at both 10% (1.88-fold increase, P < 0.001) and 20% plasma concentrations (1.63-fold increase, P = 0.019).

Conclusion In vivo, the increase in postprandial insulin concentration without a corresponding reduction in plasma glucose may reflect enhanced pancreatic β-cell responsiveness or incretin effects. In-vitro, findings suggest that NZBC extract enhances skeletal muscle GLUT4 translocation under both supraphysiological NZBC extract treatment and conditioned human serum. Although we identify a potential mechanism in vitro, the failure to observe corresponding effects in vivo underscores the complexity of translating cell-based findings to humans and suggests that additional biological factors may limit the bioactivity of NZBC extract in clinical settings.