Glucagon-like peptide-2 acutely increases proximal small intestinal blood flow in TPN-fed neonatal piglets

Glucagon-like peptide-2 (GLP-2) is a gut hormone that is secreted in response to enteral feeding and stimulates small intestinal mucosal growth. We have previously shown that GLP-2 infusion acutely increases portal venous blood flow in TPN-fed piglets. The aim of this study was to localize the vasoactive effect of GLP-2 within the gastrointestinal tissues and other visceral organs in TPN-fed piglets. Tissue blood flow rates were quantified using fluorescent microsphere deposition in anesthetized TPN-fed piglets given intravenous infusion of GLP-2 at either 500 pmol·kg−1·h−1 (low GLP-2, n = 7 pigs) or 2,000 pmol·kg−1·h−1 (high GLP-2, n = 8 pigs) for 2 h. Compared with baseline, the low and the high GLP-2 treatment significantly increased the blood flow rate in the duodenum (+77%) and jejunum (+40% and 80%), respectively, but blood flow to the distal small intestine and colon (−15%) was unchanged or slightly decreased. Baseline mucosal blood flow was five-fold higher than serosal blood flow; however, high GLP-2 treatment increased serosal (+140%) to a larger degree than mucosal blood flow (+73%). The high GLP-2 dose increased pancreatic flow (+34%) but decreased blood flow in the kidneys (−14%) and stomach (−12%), whereas the spleen and brain were unaffected. These findings suggest that the acute GLP-2-mediated stimulation of portal blood flow in TPN-fed piglets occurs principally via increased blood flow through the superior mesenteric artery to the proximal small intestine, a tissue region where the GLP-2R mRNA abundance and trophic GLP-2 effects are greatest.

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Effects of Proximal and Distal Enteral Glucose Infusion on Cardiovascular Response in Health and Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa341 ◽

2020 ◽

Vol 105 (8) ◽

pp. e2877-e2884 ◽

Cited By ~ 1

Author(s):

Xiang Zhang ◽

Karen L Jones ◽

Michael Horowitz ◽

Christopher K Rayner ◽

Tongzhi Wu

Keyword(s):

Type 2 Diabetes ◽

Blood Flow ◽

Small Intestine ◽

Cardiovascular Response ◽

Cardiovascular Responses ◽

Glucose Infusion ◽

Double Blind ◽

Distal Small Intestine ◽

Small Intestinal

Abstract Context Exposure of the small intestine to nutrients frequently leads to marked reductions in blood pressure (BP) in type 2 diabetes (T2DM). It remains unclear whether the region of the gut exposed to nutrients influences postprandial cardiovascular responses. Objective To evaluate the cardiovascular responses to proximal and distal small intestinal glucose infusion in health and T2DM. Design Double-blind, randomized, crossover design. Setting Single center in Australia. Patients 10 healthy subjects and 10 T2DM patients. Interventions Volunteers were studied on 2 occasions, when a transnasal catheter was positioned with infusion ports opening 13 cm and 190 cm beyond the pylorus. A 30-g bolus of glucose was infused into either site and 0.9% saline into the alternate site over 60 minutes. Main Outcome Measures BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow were measured over 180 minutes. Results Systolic BP was unchanged in response to both infusions in health, but decreased in T2DM, with a greater reduction after proximal versus distal infusion (all P ≤ .01). The increment in HR did not differ between treatments in health, but was greater after distal versus proximal infusion in T2DM (P = .02). The increases in SMA blood flow were initially greater, but less sustained, with proximal versus distal infusion in health (P < .001), a pattern less evident in T2DM. Conclusions In T2DM, postprandial hypotension may be mitigated by diversion of nutrients from the proximal to the distal small intestine.

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