Chicory inulin ameliorates type 2 diabetes mellitus and suppresses JNK and MAPK pathways in vivo and in vitro

Xia

et al. 2020

Microorganisms

Inulin (INU) is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. However, whether and how gut microbiota in its regulation contributes to host metabolism has yet to be investigated. We conduct this study to examine the possible associations between the gut microbiota and circulating gut microbiota–host co-metabolites induced by inulin interventions. Plasma and intestinal site samples were collected from the pigs that have consumed inulin diet for 60 days. High-throughput sequencing was adopted for microbial composition, and the GC-TOF-MS-based metabolomics were used to characterize featured plasma metabolites upon inulin intervention. Integrated multi-omics analyses were carried out to establish microbiota–host interaction. Inulin consumption decreased the total cholesterol (p = 0.04) and glucose (p = 0.03) level in serum. Greater β-diversity was observed in the cecum and colon of inulin-fed versus that of control-fed pigs (p < 0.05). No differences were observed in the ileum. In the cecum, 18 genera were altered by inulin, followed by 17 in the colon and 6 in the ileum. Inulin increased propionate, and isobutyrate concentrations but decreased the ratio of acetate to propionate in the cecum, and increased total short fatty acids, valerate, and isobutyrate concentrations in the colon. Metabolomic analysis reveals that indole-3-propionic acid (IPA) was significantly higher, and the branched-chain amino acids (BCAA), L-valine, L-isoleucine, and L-leucine are significantly lower in the inulin groups. Mantel test and integrative analysis revealed associations between plasma metabolites (e.g., IPA, BCAA, L-tryptophan) and inulin-responsive cecal microbial genera. These results indicate that the inulin has regional effects on the intestine microbiome in pigs, with the most pronounced effects occurring in the cecum. Moreover, cecum microbiota plays a pivotal role in the modulation of circulating host metabolites upon inulin intervention

Section: Discussionmentioning

confidence: 99%

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

Xia

et al. 2020

Microorganisms

“…After adaptive feeding for 1 week, rats were divided into four groups (six rats per group): Control, T2DM, and 100 and 400 mg/kg body weight AMBE groups. The Control group was maintained on a normal diet (53% carbohydrate, 23% protein, and 5% fat), whereas other rats were fed with HFD (normal diet + 20% saccharose + 15% lard stearin + 2.5% cholesterol), as described previously (Ning et al., 2017) for 4 weeks. After fasting for 24 hr, 35 mg/kg STZ was intraperitoneally injected into the rats fed with HFD, and an equal volume of citrate buffer was injected into the rats fed with normal diet.…”

Section: Methodsmentioning

confidence: 99%

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

Xin

Journal of Food Science

et al. 2020

Self Cite

We aimed to investigate) the effects of Aronia melanocarpa berry extract (AMBE) on hepatic insulin resistance and its mechanism at the molecular level in high-fat diet (HFD)-and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were supplemented with AMBE at doses of 100 and 400 mg/kg body weight (bw) daily for 8 weeks. AMBE significantly reduced blood glucose and serum insulin levels and the homeostatic model assessment for insulin resistance score; improved glucose tolerance; increased hepatic glycogen content; and regulated glucose metabolism enzyme activity, including glucokinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in the liver. AMBE also reduced lipid accumulation and oxidative stress along with inflammation in the hepatic tissue of T2DM rats and improved hepatic function. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by AMBE through the elevation of insulin receptor substrate-2, PI3K, Akt, and glycogen synthase kinase-3β phosphorylation and glucose transporter 2, which might contribute to the promotion of glycogen synthesis and improvement of hepatic insulin resistance. AMBE shows promise as an ingredient of functional foods for alleviating hepatic insulin resistance in T2DM.Keywords: Aronia melanocarpa berry, hepatic insulin resistance, PI3K/Akt signaling pathway, type 2 diabetes mellitus Practical Application: The extract from the berries of Aronia melanocarpa (Michx.) Elliott (AMBE), with its relatively high content of polyphenolic compounds, has been shown to exert hypoglycemic effects in animal models of diabetes. Our findings support the use of A. melanocarpa as a functional food additive for the alleviation of hepatic insulin resistance and the management of glucose homeostasis in T2DM.

“…Jnk has been reported to participate in many physiological processes including cell proliferation, apoptosis, and gene expression. Importantly, Jnk has also been demonstrated to be a vital mediator of noncanonical Wnt pathways and linked with diabetes and obesity[ 31 32 33 ] and liver fibrosis. [ 34 ] However, the roles of Wnt/Jnk in glucose metabolism and liver fibrosis remain enigmatic.…”

Section: Discussionmentioning

confidence: 99%

Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism

Wang

et al. 2018

Saudi J Gastroenterol

Background/Aims:Pokeweed antiviral protein (PAP) has been reported to downregulate Wnt/Jnk pathway and attenuate liver fibrosis. This study was designed to intensively explore the mechanism of anti-fibrosis effect of PAP.Materials and Methods:Hepatic stellate cell (HSC) activation was induced by high concentration of glucose. Cell viability was detected at different time points after PAP treatment. Meanwhile, hepatic fibrosis models in mice were induced by CCl4 injection. In the end, liver pathology was observed and contents of alanine transaminase, aspartate transaminase, lactic dehydrogenase, hyaluronic acid (HA), and laminin (LN) in serum together with hydroxyproline (Hyp) in liver were measured. The mRNA and protein expressions of HK2, PFKP, PCK1, and FBP1 as well as Jnk expression in HSC-T6 cells and liver tissue were detected by qPCR and western-blot, respectively.Results:Compared with high glucose, PAP reduced viability and expressions of HK2, PFKP, α-SMA, and Col1A1, where as enhanced the expressions of PCK1 and FBP1 in HSC-T6 cells (P < 0.05) respectively. PAP attenuated liver pathology, improved liver function, and reduced collagen deposition in liver tissue compared with the model group (P < 0.05) respectively. Moreover, PAP reduced expressions of HK2, PFKP, α-SMA, and Col1A1 where as increased the expression of PCK1 and FBP1 in the liver of mice compared with the model group (P < 0.05) respectively. Most importantly, PAP reduced the phosphorylation of Jnk both in cells and liver tissue compared with the model group (P < 0.05) respectively.Conclusions:Our results demonstrated that PAP attenuated liver fibrosis by regulating Wnt/Jnk-mediated glucose metabolism. It provided us a new target for the treatment of liver fibrosis.