Differential responses of the incretin hormones GIP and GLP-1 to increasing doses of dietary carbohydrate but not dietary protein in lean rats

Abstract

Previous studies have shown that oral ingestion of nutrients stimulates secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); however, it is unclear whether there is a dose-dependent response between the amount of nutrient ingested and the secretion of the hormones in vivo. Using our lymph fistula rat model, we previously demonstrated that both GIP and GLP-1 responded dose dependently to increasing amounts of infused dietary lipid and that the GLP-1-secreting cells were more sensitive to changes in intestinal lipid content. In the present study, we investigated the dose-dependent relationships between incretin secretion and the two remaining macronutrients, carbohydrate and protein. To accomplish this objective, the major mesenteric lymphatic duct of male Sprague-Dawley rats was cannulated. Each animal received a single bolus (3 ml) of saline, dextrin, whey protein, or casein hydrolysate (0.275, 0.55, 1.1, 2.2, 4.4 kcal) via a surgically inserted duodenal or ileal feeding tube. Lymph was continuously collected for 3 h and analyzed for GIP and GLP-1 content. Both GIP and GLP-1 outputs responded dose dependently to increasing amounts of dietary carbohydrate but not protein. Additionally, we found that the GIP-secreting cells were more sensitive than the GLP-1-secreting cells to changes in intestinal carbohydrate content.

Fig. 1.

Hourly lymph flow rate following a duodenal carbohydrate (A), whey protein (B), or saline bolus (0.275, 0.55, 1.1, 2.2, 4.4 kcal for each nutrient). Values are means + SE. *P < 0.05 vs. saline.

Fig. 2.

Hourly (A and C) and cumulative (B and D) lymphatic glucose-dependent insulinotropic polypeptide (GIP) output following either a duodenal carbohydrate, whey protein, or saline bolus (0.275, 0.55, 1.1, 2.2, 4.4 kcal for each nutrient). Hourly output was determined by multiplying together the lymph flow rate by the hourly GIP concentration. Cumulative secretion was calculated by summing together the hourly GIP output values during the 3-h collection period. Values are means + SE. *P < 0.05 vs. saline at time of peak secretion (A). *P < 0.05 vs. saline, #P < 0.05 vs. carbohydrate 0.275 kcal, and ^P < 0.05 vs. carbohydrate 0.55 kcal (B).

Fig. 3.

Hourly (A and C) and cumulative (B and D) lymphatic glucagon-like peptide-1 (GLP-1) output following either a duodenal carbohydrate, whey protein, or saline bolus (0.275, 0.55, 1.1, 2.2, 4.4 kcal for each nutrient). Hourly output was determined by multiplying together the lymph flow rate by the hourly GLP-1 concentration. Cumulative secretion was calculated by summing together the hourly GLP-1 output values during the 3-h collection period. Values are means + SE. *P < 0.05 vs. saline at time of peak secretion (A). *P < 0.05 vs. saline, #P < 0.05 vs. carbohydrate 0.275 kcal, and ^P < 0.05 vs. carbohydrate 0.55 kcal (B).

Fig. 4.

Cumulative lymphatic GIP (A) and GLP-1 (B) output plotted as a function of nutrient dose. Five carbohydrate (●) and 5 whey protein (□) doses were tested (0.275, 0.55, 1.1, 2.2, 4.4 kcal for each nutrient). Values (fold amounts above saline) are means + SE. Equations for best-fit lines generated for GIP and GLP-1 are shown. Only the slopes for the carbohydrate best-fit lines were significantly greater than zero (P < 0.001, carbohydrate GIP; P < 0.001, carbohydrate GLP-1; P = 0.209, protein GIP; P = 0.228, protein GLP-1).

Fig. 5.

Hourly lymphatic GIP (A) and GLP-1 (B) output following either an ileal carbohydrate (carb; 0.275, 0.55, 1.1 kcal) or saline bolus. Hourly output was determined by multiplying together the lymph flow rate by the hourly GIP or GLP-1 concentration. Values are means + SE. *P < 0.05 vs. saline at time of peak secretion. Cumulative lymphatic GIP and GLP-1 output plotted a function of carbohydrate dose. Three ileal (C) and 3 duodenal (D) doses were tested (0.275, 0.55, 1.1 kcal). Values (fold amounts above saline) are means + SE. Equations for best-fit lines generated for GIP and GLP-1 are shown. All of the slopes for the best-fit lines were significantly greater than zero.

Fig. 6.

Cumulative lymphatic GIP (A) and GLP-1 (B) output following either a duodenal whey protein, protein hydrolysate, or saline bolus (0.275, 1.1, 4.4 kcal for each nutrient). Cumulative secretion was calculated by summing together the hourly GIP or GLP-1 output values during the 3-h collection period. Values are means + SE. *P < 0.05: protein vs. protein hydrolysate at that dose.