Multifaceted interplay among mediators and regulators of intestinal glucose absorption: potential impacts on diabetes research and treatment

Abstract

Chan LK, Leung PS. Multifaceted interplay among mediators and regulators of intestinal glucose absorption: potential impacts on diabetes research and treatment. Am J Physiol Endocrinol Metab 309: E887-E899, 2015. First published October 20, 2015 doi:10.1152/ajpendo.00373.2015-Glucose is the prominent molecule that characterizes diabetes and, like the vast majority of nutrients in our diet, it is absorbed and enters the bloodstream directly through the small intestine; hence, small intestine physiology impacts blood glucose levels directly. Accordingly, intestinal regulatory modulators represent a promising avenue through which diabetic blood glucose levels might be moderated clinically. Despite the critical role of small intestine in blood glucose homeostasis, most physiological diabetes research has focused on other organs, such as the pancreas, kidney, and liver. We contend that an improved understanding of intestinal regulatory mediators may be fundamental for the development of first-line preventive and therapeutic interventions in patients with diabetes and diabetes-related diseases. This review summarizes the major important intestinal regulatory mediators, discusses how they influence intestinal glucose absorption, and suggests possible candidates for future diabetes research and the development of antidiabetic therapeutic agents.insulin; glucagon; oxyntomodulin; glucagon-like peptide-1 and -2; glucose-dependent insulinotropic polypeptide; cholecystokinin; catecholamines; renin-angiotensin system; angiotensin ii; leptin; niacin; polyphenols DIABETES (TYPE 1 OR 2 DIABETES MELLITUS, T1DM or T2DM) is a chronic metabolic disease characterized by hyperglycemia that can result from insulin insufficiency and/or insulin resistance. Currently, there are over 300 million diabetic patients, among them 5% being T1DM and 90 -95% being T2DM (179). The chronic hyperglycemic state associated with diabetes produces a number of hallmark clinical manifestations, including pathologies of the eyes, kidneys, heart, blood vessels, and nerves.The vast majority of therapeutic interventions for diabetes target the pancreas, liver, skeletal muscle, adipose tissues, or kidney. Research examining diabetes interventions targeting the small intestine has been somewhat lacking. In this regard, it is important to note that postprandial hyperglycemia has been shown to be closely related to an elevated risk of developing T2DM (88, 122). Given the fundamental role of the small intestine in the absorption of food nutrients, especially glucose, a deeper understanding of the regulators of intestinal glucose uptake would be beneficial for devising new therapeutic strategies, such as potential manipulations of these regulators in the small intestine.Despite its name, the small intestine is not at all "small" in the sense that it absorbs over 90% of consumed nutrients, leaving only a minority of nutrients to be absorbed by other parts of the intestines. The small intestine is crucial for delivering dietary glucose, as well as substrate molecules...

Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

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Guava (Psidium guajava) Fruit Extract Prepared by Supercritical CO2 Extraction Inhibits Intestinal Glucose Resorption in a Double-Blind, Randomized Clinical Study

“…A possible strategy to reduce postprandial glucose and subsequent insulin peaks is the inhibition of intestinal glucose absorption. In general, glucose is absorbed across the small intestine through brush border cells via sodium-dependent glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) [4]. The search for appropriate antidiabetic agents has recently been focused on plants, as plant-derived extracts contain bioactive ingredients that inhibit sugar absorption [5].…”

Na+/H+ exchanger 3 blockade ameliorates type 2 diabetes mellitus via inhibition of sodium‐glucose co‐transporter 1‐mediated glucose absorption in the small intestine

“…The significance of the small intestine in glucose homeostasis is further underscored by the recent discovery of a gut–brain–liver axis, and its interplay in glucose metabolism . Moreover, there exists an intricate interplay among various regulators in the small intestine for mediating intestinal glucose absorption . Despite these findings, the vast majority of antidiabetic drugs currently on the market focus on such organs as the pancreas, liver and kidney.…”

“…[4][5][6][7] Moreover, there exists an intricate interplay among various regulators in the small intestine for mediating intestinal glucose absorption. 8 Despite these findings, the vast majority of antidiabetic drugs currently on the market focus on such organs as the pancreas, liver and kidney. The small intestine remains an attractive yet unexplored target for glycaemic control.…”