Regulation of proglucagon derived peptides by carbohydrate and protein ingestion in young healthy males-A randomized, double-blind, cross-over trial

Background & aims: The ingestion of macronutrients triggers the release of several incretin peptides from the gastrointestinal system, which have both insulinotropic and satiety-inducing properties. The effect of the meal's macronutrient content on the secretion of these peptides has not been adequately studied, particularly concerning the secretion of the newly characterized proglucagon-derived peptides (PGDPs). We aimed to examine the effect of a meal's macronutrient content, specifically its protein versus carbohydrate content, on postprandial PGDPs responses in healthy men.

Methods: Ten apparently healthy, normal-weight males completed a trial consisting of two interventions in a randomized, double-blind, crossover design. In one intervention, participants consumed an isocaloric high-protein breakfast (65 g of glucose, 60 g of protein), while in the other, participants consumed a carbohydrate-rich breakfast (125 g of glucose). Levels of all seven PGDPs, namely glucagon-like peptide-1 and -2 (GLP-1 and GLP-2), oxyntomodulin, glicentin, major pro-glucagon fragment (MPGF), glucagon and proglucagon, as well as glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide total and total plus (GIP total and GIP total plus) levels were measured at baseline, every 15 minutes for the first hour and every 30 minutes for the second and third hours after each meal.

Results: The two interventions produced similar glycemic and insulinemic responses, while total amino acids increased more over time in response to protein administration. Levels of proglucagon (F(8) = 4.114, p = 0.001) and the primarily pancreas-secreted glucagon and MPGF (F(8) = 3.088, p = 0.005) rose significantly during the protein intervention. GIP total and GIP total plus increased in response to carbohydrate ingestion. No major overall differences were observed for the primarily intestinally secreted GLP-1, oxyntomodulin and glicentin between the two arms of the trial, although their levels tended to increase earlier in response to carbohydrates and later in response to protein administration, especially in the case of GLP-2 levels.

Conclusions: The carbohydrate vs. protein content of a meal differentially increases the levels of GIP and PGDPs during the postprandial period. Dose-response studies and comparisons with lipid intake may further advance our knowledge of the physiology of these clinically important molecules and their implications in energy homeostasis.