Abstract
Despite the updated knowledge of the impact of gut dysbiosis on diabetes, investigations into the beneficial effects of individual bacteria are still required. This study evaluates the antihyperglycemic efficacy of Lactobacillus paracasei HII01 and its possible mechanisms in diabetic rats. Diabetic rats were assigned to receive vehicle, L. paracasei HII01 (108 CFU/day), metformin 30 (mg/kg) or a combination of L. paracasei HII01 and metformin. Normal rats given vehicle and L. paracasei HII01 were included. Metabolic parameters, including in vitro hemi-diaphragm glucose uptake, skeletal insulin-signaling proteins, plasma lipopolysaccharide (LPS), gut permeability, composition of gut microbiota and its metabolites, as well as short-chain fatty acids (SCFAs), were assessed after 12 weeks of experiment. The results clearly demonstrated that L. paracasei HII01 improved glycemic parameters, glucose uptake, insulin-signaling proteins including pAktSer473, glucose transporter 4 (GLUT4) and phosphorylation of AMP-activated protein kinase (pAMPKThr172), tumor necrosis factor (TNF-α) and nuclear factor-κB (NF-kB) in diabetic rats. Modulation of gut microbiota was found together with improvement in leaky gut, endotoxemia and SCFAs in diabetic rats administered L. paracasei HII01. In conclusion, L. paracasei HII01 alleviated hyperglycemia in diabetic rats primarily by modulating gut microbiota along with lessening leaky gut, leading to improvement in endotoxemia and inflammation-disturbed insulin signaling, which was mediated partly by PI3K/Akt signaling and AMPK activation.
Highlights
IntroductionAccording to the International Diabetes Federation (IDF), the number of diabetic patients worldwide was 425 million in 2017 and will rise to 629 million by 2045 [1]
Type 2 diabetes mellitus (T2DM), a multifactorial metabolic endocrine disorder, is characterized by persistent hyperglycemia, and it is basically a result of insulin resistance and impaired β-cell function.According to the International Diabetes Federation (IDF), the number of diabetic patients worldwide was 425 million in 2017 and will rise to 629 million by 2045 [1]
Following 12 weeks of oral administration of L. paracasei HII01, the Body Weight (BW), Visceral Fat (VF) weight and VF/100 g BW did not differ among the normal rats
Summary
According to the International Diabetes Federation (IDF), the number of diabetic patients worldwide was 425 million in 2017 and will rise to 629 million by 2045 [1]. Several influences such as genetics, age, unhealthy lifestyle and obesity are accepted as risk factors of T2DM [2]. Changes in gut microbiota composition, known as gut dysbiosis, have been associated with disrupted gut barrier functions and increased gut permeability [4,5]. The enhancement of gut permeability might result in bacterial lipopolysaccharide (LPS) leak into blood circulation, followed by inflammatory activation through the LPS-Toll-like receptor 4-Nuclear factor-κB (LPS-TLR4-NF-kB) signaling pathway [6,7]
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