Glucose-dependent insulinotropic polypeptide stimulates post-absorptive lipid secretion in the intestine

Abstract

It is increasingly recognized that the intestine can retain a portion of dietary fats for secretion during the post-absorptive state, which has strong implications in metabolic diseases. The regulatory mechanisms of gut lipid storage and release are not well defined. Previous studies showed that the intestine releases locally stored fats in response to several stimulatory cues, such as glucose delivered into the intestinal lumen. It remains unknown how the intestine responds to nutrient signals in this phenomenon. Here we tested the effects of intravenous glucose delivery on intestinal lipid output during the post-absorptive state in mesenteric lymph duct cannulated rats. Compared with intraduodenal glucose delivery, intravenous glucose did not stimulate intestinal lipid output. Intraduodenal glucose was also associated with increases in blood levels of metabolic hormones, among which glucose-dependent insulinotropic peptide (GIP) levels were significantly higher at timepoints corresponding to increased lipid output than in intravenous glucose. Intraperitoneal GIP administration per se robustly stimulated intestinal lipid output. These results support a mechanism that involves glucose sensing at the apical side of the enterocytes and GIP as a potent stimulus for the release of lipid storage from the intestine.

Keywords: chylomicron; glucose; glucose-dependent insulinotropic peptide; intestine; triglycerides.

FIGURE 1

Intraduodenal (ID) but not intravenous (IV) delivery of glucose increases lymph fluid and TG output from the gut during post-absorptive state. (A) Lymph flow rate, (B) TG concentration, (C) TG output and (D) TG output expressed as % change from t = 0 during the experiment. Data are mean ± SEM. n = 7 each group. *p < 0.05, **p < 0.01 IV vs. ID.

FIGURE 2

Intraduodenal (ID) but not intravenous (IV) delivery of glucose increases apolipoprotein B48 output from the gut during post-absorptive state. (A) Lymph ApoB48 concentration and (B) lymph apoB48 output during the experiment. Data are mean ± SEM. n = 7 each group. *p < 0.05 IV vs. ID.

FIGURE 3

Intraduodenal (ID) and intravenous (IV) delivery of glucose lead to differences in circulating levels of glucose and glucose-responsive hormones. Serum concentrations (left) and AUC (right) of (A) glucose, (B) insulin, (C) C-peptide 2 and (D) glucagon. Data are mean ± SEM. n = 7 each group. *p < 0.05, ***p < 0.001 IV vs. ID.

FIGURE 4

Intraduodenal (ID) and intravenous (IV) delivery of glucose lead to differences in circulating levels of incretin hormones. Serum concentrations (left) and AUC (right) of (A) GLP-1 and (B) GIP. Data are mean ± SEM. n = 7 each group. *p < 0.05, **p < 0.01 IV vs. ID.

FIGURE 5

Intraperitoneal administration of GIP increases lymph fluid and TG output from the gut during post-absorptive state. (A) Lymph flow rate, (B) TG concentration and (C) TG output during the experiment, and (D) Total Lymph Volume and Total TG Output during the first hour. Data are mean ± SEM. n = 7 each group. *p < 0.05, **p < 0.01, ***p < 0.001 GIP vs. PBS.

FIGURE 6

Intraperitoneal administration of GIP increases apolipoprotein B48 output from the gut during post-absorptive state. (A) Lymph ApoB48 concentration and (B) lymph apoB48 output during the experiment. Data are mean ± SEM. n = 7 each group. *p < 0.05, **p < 0.01 GIP vs. PBS.