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Glucose and GLP-2 (Glucagon-Like Peptide-2) Mobilize Intestinal Triglyceride by Distinct Mechanisms.

OBJECTIVE
Dietary triglycerides are partially retained in the intestine within intracellular or extracellular compartments, which can be rapidly mobilized in response to several stimuli, including glucose and GLP-2 (glucagon-like peptide-2). To elucidate the mechanism of intestinal lipid mobilization, this study examined the patterns and time course of lymph flow and triglycerides after glucose and GLP-2 treatment in rats. Approach and Results: Lymph flow, triglyceride concentration, and triglyceride output were assessed in mesenteric lymph-cannulated rats in response to an intraduodenal (i.d.) lipid bolus followed 5 hours later by either (1) i.d. saline+intraperitoneal (i.p.) saline (placebo), (2) i.d. glucose plus i.p. saline, (3) i.d. saline+i.p. GLP-2, or (4) i.d. glucose+i.p. GLP-2. GLP-2 and glucose administered alone or in combination stimulated total triglycerides output to a similar extent, but the timing and pattern of stimulation differed markedly. Whereas GLP-2 rapidly increased lymph flow with no effect on lymph triglyceride concentration or triglycerides:apoB48 (apolipoprotein B48) ratio (a surrogate marker of chylomicron size) compared with placebo, glucose transiently decreased lymph flow followed by delayed stimulation of lymph flow and increased lymph triglycerides concentration and triglycerides:apoB48 ratio.


CONCLUSIONS
Glucose and GLP-2 robustly enhanced intestinal triglyceride output in rats but with different effects on lymph flow, lymph triglycerides concentration, and chylomicron size. GLP-2 stimulated triglycerides output primarily by enhancing lymph flow with no effect on chylomicron size, whereas glucose mobilized intestinal TG, stimulating secretion of larger chylomicrons. This suggests that these 2 stimuli mobilize intestinal lipid by different mechanisms.