Genistein ameliorates inflammation and insulin resistance through mediation of gut microbiota composition in type 2 diab
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ORIGINAL CONTRIBUTION
Genistein ameliorates inflammation and insulin resistance through mediation of gut microbiota composition in type 2 diabetic mice Rui Yang1,2 · Qiang Jia1 · Shomaila Mehmood2 · Shanfeng Ma1 · Xiaofen Liu1 Received: 5 June 2020 / Accepted: 2 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Genistein (GEN) has been reported to have diverse biological activities, including antioxidant, hypolipidemic, and antidiabetic effects. This study investigated whether the ameliorative effects of GEN on inflammation and insulin resistance were associated with the modulation of gut microbiota composition in type 2 diabetic (T2D) mice. Methods C57BL/6J mice were treated with a high-fat diet/streptozotocin to induce T2D and then gavaged with GEN (20 and 40 mg/kg) for 8 weeks. Then, oral glucose tolerance, fasting blood glucose, serum insulin, glucagon, lipid profiles, and pro-inflammatory factors were measured. After this, hepatic function and histopathological analysis and inflammation-related indices of the liver and colon were determined, along with short-chain fatty acid (SCFA) and gut microbiota composition. Results GEN treatment decreased hyperglycemia, hyperlipidemia, and serum pro-inflammatory factor levels and attenuated hepatic dysfunction, pathological changes, inflammation-related protein expression, and hepatocyte apoptosis. It also ameliorated colonic pathological changes, tight junction-associated protein expression, and pro-inflammatory factor increases. Furthermore, high-dose GEN treatment increased the concentrations of SCFAs and down-regulated the ratio of Firmicutes/ Bacteroidetes and the abundance of Proteobacteria at the phylum level. However, GEN increased the abundances of Bacteroides and Prevotella and decreased the levels of Helicobacter and Ruminococcus at the genus level in T2D mice. Conclusion GEN showed ameliorative effects on glucose and lipid dysmetabolism and hepatic and colonic dysfunction; most importantly, GEN could ameliorate inflammation and insulin resistance through modulation of gut microbiota composition. Keywords Genistein · Diabetes · Inflammation · Insulin resistance · Gut microbiota
Introduction Diabetes mellitus, commonly referred to as diabetes, is a cluster of chronic metabolic abnormalities, comprising type 1 diabetes, type 2 diabetes (T2D), gestational diabetes, and other rare forms of diabetes [1]. Of these, T2D accounts for around 90% of all cases and is associated with high rates of mortality due to the presence of many serious complications, such as nephropathy, retinopathy, and cardiovascular disease [2, 3]. Although the pathogenesis of T2D is very * Qiang Jia [email protected] 1
Department of Physiology, Bengbu Medical College, Bengbu 233030, China
School of Life Sciences, Anhui University, Hefei 230601, China
2
complicated, it is clear that insulin secretion deficiency of pancreatic beta cells and insulin resistance (IR) are the two major causes [4, 5]. Emerging data suggest that gut microbiota–
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