Putative Mechanisms Responsible for the Antihyperglycemic Action of Lactobacillus paracasei HII01 in Experimental Type 2 Diabetic Rats

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.

Alteration of Gut Microbiota Relates to Metabolic Disorders in Primary Aldosteronism Patients

“…In addition, Lactobacillus was more abundant in the gut microbiota of healthy controls and primary hypertension patients than in PA patients. Several studies have already demonstrated that the administration of Lactobacillus could alleviate hyperglycemia in diabetic rats (6,24,25). We also found that Lactococcus and Enterococcus were present in lower abundances in PA patients.…”

Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice

“…Although antibacterial effects of metformin are not fully understood, the underlying metabolic mechanisms of metformin are widely attributed to the activation of AMPK [ 65 ]. Toejing et al found that metformin ameliorates endotoxemia and inflammation through the AMPK-NF- κ B pathway [ 31 , 66 ]. Mammalian AMPK is generally thought of as a sensor for adenine nucleotides, activated in a state of low cellular energy.…”

Influence of Lactobacillus paracasei HII01 Supplementation on Glycemia and Inflammatory Biomarkers in Type 2 Diabetes: A Randomized Clinical Trial

“…Another probable pathway mediating the connection between gut microbiota and metabolic endotoxemia is gut permeability [ 4 ]. Our previous study demonstrated that supplementation with the L. paracasei HII01 for 12 weeks in T2DM rat resulted in lessening plasma levels of DX-4000-FITC, suggesting an improvement of gut barrier integrity [ 38 ]. This effect could directly ameliorate systemic endotoxemia by reducing the leakage of LPS into systemic circulation.…”

“…These SCFAs are not only of importance in gut health as signaling molecules but might also enter the systemic circulation and directly affect peripheral tissues via AMPK activation and subsequently GLUT4 translocation to membrane for uptake of glucose into cells [ 45 ]. In addition, our previous study found that supplementation of L. paracasei HII01 alleviated hyperglycemia in diabetic rats via increasing glucose uptake by the skeletal muscle which was mediated partly by PI3K/Akt and AMPK activation [ 38 ].…”