Dataset Information

Flos Lonicera Combined with Metformin Ameliorates Hepatosteatosis and Glucose Intolerance in Association with Gut Microbiota Modulation.

ABSTRACT: The gut microbiota is important in energy contribution, metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with chronic metabolic diseases like type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Metformin (MET) and Flos Lonicera (FL) are common treatments for metabolic diseases in Western and Oriental medicinal fields. We evaluated the effect of treatment with FL and MET in combination on hepatosteatosis, glucose tolerance, and gut microbial composition. FL and MET were administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of genetic T2D and NAFLD. The FL+MET treatment reduced liver weight, serum cholesterol, insulin resistance, and hepatic MDA level and modulated the gut microbial composition. More specifically, the genera of Prevotella and Lactobacillus were negatively associated with the body and liver weights, hepatic TG and TC content, and serum insulin level. However, the relative abundance of these genera decreased in response to the FL+MET treatment. Interestingly, pathway prediction data revealed that the FL+MET treatment attenuated lipopolysaccharide-related pathways, in keeping with the decrease in serum and fecal endotoxin levels. FL and MET in combination exerts a synergistic effect on the improvement of hepatosteatosis and insulin sensitivity in OLETF rats, and modulates gut microbiota in association with the effect.

SUBMITTER: Shin NR

PROVIDER: S-EPMC5698303 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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<i>Flos Lonicera</i> Combined with Metformin Ameliorates Hepatosteatosis and Glucose Intolerance in Association with Gut Microbiota Modulation.

Shin Na R NR Bose Shambhunath S Wang Jing-Hua JH Ansari AbuZar A Lim Soo-Kyoung SK Chin Young-Won YW Choi Han-Seok HS Kim Hojun H

Frontiers in microbiology 20171117

The gut microbiota is important in energy contribution, metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with chronic metabolic diseases like type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Metformin (MET) and <i>Flos Lonicera</i> (FL) are common treatments for metabolic diseases in Western and Oriental medicinal fields. We evaluated the effect of treatment with FL and MET in combination on hepatosteatosis, ...[more]

PMID: 29204141

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Project description:ObjectivePancreatic ?-cell failure is central to the development and progression of type 2 diabetes (T2D). The aggregation of human islet amyloid polypeptide (hIAPP) has been associated with pancreatic islet inflammation and dysfunction in T2D. Alpha1-antitrypsin (AAT) is a circulating protease inhibitor with anti-inflammatory properties. Here, we sought to investigate the potential therapeutic effect of AAT treatment in a mouse model characterized by hIAPP overexpression in pancreatic ?-cells.MethodsMice overexpressing hIAPP (hIAPP-Tg) in pancreatic ?-cells were used as a model of amyloid-induced ?-cell dysfunction. Glucose homeostasis was evaluated by glucose tolerance tests and insulin secretion assays. Apoptosis and amyloid formation was assessed in hIAPP-Tg mouse islets cultured at high glucose levels. Dissociated islet cells were cocultured with macrophages obtained from the peritoneal cavity.ResultsNontreated hIAPP-Tg mice were glucose intolerant and exhibited impaired insulin secretion. Interestingly, AAT treatment improved glucose tolerance and restored the insulin secretory response to glucose in hIAPP-Tg mice. Moreover, AAT administration normalized the expression of the essential ?-cell genes MafA and Pdx1, which were downregulated in pancreatic islets from hIAPP-Tg mice. AAT prevented the formation of amyloid deposits and apoptosis in hIAPP-Tg islets cultured at high glucose concentrations. Since islet macrophages mediate hIAPP-induced ?-cell dysfunction, we investigated the effect of AAT in cocultures of macrophages and islet cells. AAT prevented hIAPP-induced ?-cell apoptosis in these cocultures without reducing the hIAPP-induced secretion of IL-1? by macrophages. Remarkably, AAT protected ?-cells against the cytotoxic effects of conditioned medium from hIAPP-treated macrophages. Similarly, AAT also abrogated the cytotoxic effects of exogenous proinflammatory cytokines on pancreatic ?-cells.ConclusionsThese results demonstrate that treatment with AAT improves glucose homeostasis in mice overexpressing hIAPP and protects pancreatic ?-cells from the cytotoxic actions of hIAPP mediated by macrophages. These results support the use of AAT-based therapies to recover pancreatic ?-cell function for the treatment of T2D.

Project description:Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change (P < 0.001), and baseline glucose levels explained 10% of variation (P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 (P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

Dataset Information

Flos Lonicera Combined with Metformin Ameliorates Hepatosteatosis and Glucose Intolerance in Association with Gut Microbiota Modulation.

Publications

<i>Flos Lonicera</i> Combined with Metformin Ameliorates Hepatosteatosis and Glucose Intolerance in Association with Gut Microbiota Modulation.

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