Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice

Abstract

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors.

Inulin Inhibits the Inflammatory Response through Modulating Enteric Glial Cell Function in Type 2 Diabetic Mellitus Mice by Reshaping Intestinal Flora

“…Currently, the role of the inflammatory response in promoting the pathological processes in T2DM and its impact on affected tissues and organs is well recognized. Several studies have provided insights into the mechanisms by which T2DM induces inflammation and oxidative stress. – It is indisputably beneficial to modulate the inflammatory response in T2DM patients. – The cardiovascular, renal, and other organ-protective effects of novel antidiabetic medications have been attributed to their anti-inflammatory properties . Colonic inflammation, with its detrimental effects on the mucosal barrier, bacterial infection, and insulin resistance, has been implicated in various diseases, including diabetes.…”

“… 21 – 25 The cardiovascular, renal, and other organ-protective effects of novel antidiabetic medications have been attributed to their anti-inflammatory properties. 26 Colonic inflammation, with its detrimental effects on the mucosal barrier, bacterial infection, and insulin resistance, has been implicated in various diseases, including diabetes. A growing body of evidence has shown an association between the development of T2DM and its complications with a state of chronic inflammation.…”

Quercetin Alleviates Insulin Resistance and Repairs Intestinal Barrier in db/db Mice by Modulating Gut Microbiota

“…It has been shown that inflammatory response and increased oxidative stress may be crucial factors in the development of T2DM [ 7 , 8 ]. Intestinal inflammatory damage is one of the metabolic disorders induced by diabetes [ 9 ]. Many studies have demonstrated that patients with type 2 diabetes are accompanied by disturbances of the intestinal microbiota and disruption of intestinal permeability, which can cause damage to multiple organs and lead to a number of complications [ 10 , 11 , 12 ].…”