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Lachlan T. MacLean Ryan T. Bevington Adham H.H.G. Ibrahim

Abstract

Introduction: Nutrient and gas exchange via microvascular blood flow is a key process of circulatory function. There is a significant decrease in the microvascular blood flow to skeletal muscle after orally ingesting glucose. Incretins like glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), are released in response to glucose in the gut, stimulating insulin release.  Our protocol plans to investigate if incretins and the subsequent insulin release contribute to the decrease in microvascular blood flow.


Methods: 20 healthy young adults will consume a high glucose mixed nutrient meal. Using contrast-enhanced ultrasound (CEU) and a blood glucose meter, microvascular blood flow and blood glucose will be measured. Blood GLP-1 and GIP will be measured using a sandwich enzyme immunoassay, while an electrochemiluminescence technique using an autoanalyzer will measure insulin. Measurements will be recorded at 0, 1, and 2 hours post-prandial. In a randomized order, the protocol will be repeated with infusion of GIP and GLP-1 inhibitors, GIP(3-30)NH2 and exendin(9-39)NH2 or saline.


Results: With normal incretin secretion, we anticipate a significant decrease in microvascular blood flow, along with an increase in blood insulin, GIP/GLP-1 levels. We postulate that supressing incretins will increase the microvascular blood flow along with decreased plasma insulin and no change in GLP-1/GIP levels.


Discussion: Through our methods, we propose a study design which evaluates the relationship of incretins and insulin on post-prandial microvascular blood flow. Our expected results aim to provide data that can be applied to the progressive treatment of type II diabetes with incretins like GLP-1.  Understanding the impact of incretin treatment on the microvascular blood flow could be beneficial to the discovery of an adverse effect or how glucose uptake in peripheral tissues is altered. These are vital aspects of developing a clinical treatment to diabetes and our results will provide a basis to work off.


Conclusion: The goal of this protocol was to investigate and provide insight to fully understand incretins and their effects. It will propel research on the biochemical pathways involving incretin and microvascular blood flow, which then helps progress treatment of complications like diabetes.

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Section
Research Protocol