Grape Powder Reverses Deleterious Effects of GLP‐1 Receptor Antagonism on Oral Glucose Tolerance in Mice

Abstract

The mechanism by which grapes and grape flavan‐3‐ols improve glycemic control is poorly understood. Studies have shown that dietary flavan‐3‐ols may act in the gut to increase secretion of incretins such as glucagon‐like peptide‐1 (GLP‐1). Our objectives were to determine the impact of grapes on GLP‐1 signaling and acute glycemic control, and compare the effects of grape administration to the gut vs. peripheral tissues. The impact of a GLP‐1 receptor antagonist (vs. vehicle) on oral glucose tolerance was studied in mice administered either grape powder (a substitute for fresh grapes) or control. Additionally, the effect of delivering grape (or control) orally vs. to the intraperitoneal (i.p.) cavity was examined. In control mice, GLP‐1 receptor antagonism significantly increased oral glucose area under the curve (AUC) vs. vehicle. While grape powder did not lower AUC in vehicle‐treated mice compared to vehicle‐treated control, it did inhibit the deleterious effects of GLP‐1 receptor antagonism compared to GLP‐1 receptor antagonism in control mice. This suggests that grapes may not affect normal glucose metabolism, but may prevent the negative effects of a blunted incretin response in prediabetes and diabetes. However, the mechanism remains unknown. Administration of grape powder to peripheral tissues (via i.p. injection) resulted in significantly elevated oral glucose AUC compared to oral administration of grape powder. This suggests that increased bioavailability of grape constituents to peripheral tissues (i.e. skeletal muscle) may not results in improved anti‐diabetic activities. This research was funded by The California Table Grape Commission.