Mechanistic Insights Into Postprandial Insulin-Glucagon Interactions and Their Impact on Glucose Flux After Protein-Glucose Coingestion in Humans.

Abstract

Despite stimulating glucagon secretion, the mechanisms by which protein ingestion lowers glucose excursions remain unclear. We investigated this using the triple stable isotope glucose tracer technique to measure postprandial glucose fluxes. Eleven healthy adults completed three trials, ingesting 25 g glucose (25G; 100 kcal), 50 g glucose (50G; 200 kcal), or 25 g glucose plus 25 g whey protein (25WG; 200 kcal). Glucose excursions were lowest for 25WG. Glucagon increased approximately threefold with 25WG but was suppressed with 25G and 50G. Insulin and glucose-dependent insulinotropic polypeptide (GIP) were higher for 25WG versus 25G, whereas glucagon-like peptide 1 (GLP-1) was similar. Compared with 50G, 25WG produced a greater GIP but similar GLP-1 response, with a trend toward higher early-phase insulin. Endogenous glucose production (EGP) was less suppressed with 25WG (∼50%) versus 25G (∼70%) or 50G (∼80%). Compared with 25G, 25WG did not enhance glucose disposal (Rd) but reduced early-phase (30-60 min) glucose absorption. These findings confirm that protein-glucose coingestion robustly stimulates glucagon while enhancing GIP and insulin, leading to lower postprandial glucose excursions. Despite greater insulin secretion, the net glycemic benefit seems to stem from reduced early glucose absorption rather than increased Rd. This provides novel insights into the mechanisms by which protein improves postprandial glucose handling despite interfering with EGP suppression.

Article highlights: Despite stimulating glucagon secretion, the addition of protein to carbohydrate typically lowers postprandial glucose excursions. The mechanisms underlying this phenomenon are incompletely understood. In healthy young adults, using the triple stable isotope glucose tracer technique, we investigated how whey protein and glucose coingestion modulates postprandial glucose fluxes. Despite stimulating glucagon secretion and impairing suppression of endogenous glucose production, whey protein-glucose coingestion significantly reduced glycemic excursions. Although whey protein-glucose coingestion strongly enhanced the insulin and glucose-dependent insulinotropic polypeptide (but not glucagon-like peptide 1) responses, whole-body glucose uptake was not enhanced; rather, the net glycemic benefit seemed to stem from reduced early-phase glucose absorption.