GLP-2: A Poorly Understood Mediator Enrolled in Various Bariatric/Metabolic Surgery-Related Pathophysiologic Mechanisms

Abstract

Introduction: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa. Aim: Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications. Methods: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected. Results: There is evidence demonstrating significant increase in the levels of GLP-2 following gastric bypass, Scopinaro operation, and sleeve gastrectomy. There are no differences between gastric bypass and sleeve gastrectomy in regards to the increase in the GLP-2 levels. There is no correlation between the postoperative levels of GLP-2 and the occurrence of adequate or insufficient postoperative weight loss. Conclusion: GLP-2 plays significant roles on the regulation of nutrient absorption, permeability of gut mucosa, control of bone resorption, and regulation of satiety. The overall impact of these effects potentially exerts a significant adaptive or compensatory effect within the context of varied bariatric surgical techniques.

GLP-2 receptor signaling controls circulating bile acid levels but not glucose homeostasis in Gcgr mice and is dispensable for the metabolic benefits ensuing after vertical sleeve gastrectomy

“…These observations have fostered a vigorous debate surrounding the putative contribution(s) of GLP-1 action to the weight loss and improved glucose control evident following metabolic surgery [20] , [21] , [22] . Remarkably, although circulating GLP-2 levels are also considerably elevated after metabolic surgery [51] , there has been little attention directed at examining whether GLP-2 receptor signaling contributes to the metabolic improvement after RYGB or VSG.…”

“…Second, Gcgr −/− mice are relatively resistant to development of diabetes and obesity [55] ; hence, the data generated here in non-obese Gcgr −/− mice may not be relevant to findings obtained with transient Gcgr antagonism in more obese or diabetic mice or humans. Furthermore, although plasma levels of PGDPs, including GLP-2, are elevated in mice, rats and humans after VSG [20] , [21] , [51] , it is possible that GLP-2 levels may be elevated to a greater extent, and the biology of GLP-2R may be more important, in experimental models analyzing the metabolic consequences of RYGB. Surprisingly, despite multiple reports linking GLP-2 to the control of appetite, glucose homeostasis, and insulin sensitivity, our data using two different experimental models characterized by increased levels of PGDPs failed to demonstrate a key role for the GLP-2R in regulation of glucose control or body weight evident after disruption of Gcgr signaling, or following VSG.…”

Comparison of the Levels of C-Reactive Protein, GLP-1 and GLP-2 Among Individuals With Diabetes, Morbid Obesity and Healthy Controls: An Exploratory Study

“…It is secreted by means of proteolytic cleavage of proglucagon in response to the passage of nutrients through the distal small bowel, in a 1:1 ratio with glucagon-like peptide 1 (GLP-1) in a process mediated by enzymes proglucagon convertase 1/3 (1)(2)(3)(4)(5)(6)(7)(8) . Although the properties of GLP-2 have not been completely elucidated to date, it presents several known physiologic functions, of which the main are the trophic effect on the gut mucosa and the enhancement of nutrient absorption (5)(6)(7)(8)(9)(10)(11)(12)(13) . GLP-1 is mainly enrolled in glucose homeostasis, and its main effects are the increasing of pancreatic beta cell function and the improvement of insulin sensitivity (14,15) .…”

“…A witty metaphor proposed by Hein et al (23) claimed that GLP-1 and GLP-2 were "the yin and yang" of intestinal lipoprotein production, since GLP-1 significantly reduces and GLP-2 increases postprandial chylomicronemia. A likely assertion can be made in regards of glucose metabolism, since GLP-1 is enrolled in decreasing postprandial blood glucose levels by means of insulin release, whereas GLP-2 enhances glucose absorption and thus increases the postprandial glucose levels (9,10,12,13,15,24,25) . The physiological roles of GLP-1 and GLP-2 are consistently pronounced in individuals who have undergone bariatric surgery (17,19) .…”

Mini-Gastric Bypass: Description of the Technique and Preliminary Results

“…Bariatric surgery has been performed with increasing frequency around the world over the last decades, especially because of the extremely superior results in relation to long-term sustained weight loss and resolution of comorbidities than those observed with non-surgical therapies 4 , 5 , 7 , 8 , 27 . The overall impact of bariatric surgery has been demonstrated, with reductions of 40% on the mortality for any cause, 56% for coronary disease, 92% for complications of diabetes, and 60% for any malignant neoplasia 1 .…”