Abstract

Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.

Highlights

  • Prediabetes (PreD) refers to an intermediary phase between healthy state and diabetes disease where glycaemia is altered but still below the threshold for the diagnosis of diabetes

  • We have investigated the blood glucose-control effect of the probiotic pA1c in in vivo animal models through the evaluation of the main biochemical parameters implicated in the risk for PreD development, including those used for PreD diagnosis (FBG and Glucose tolerance tests (GTTs)) [1], and others such as BW, HOMA-insulin resistance (IR), or circulating C-peptide [2,47]

  • With the purpose to verify the improvement in insulin sensitivity induced by pA1c, we studied GTT and HOMA-IR index as indirect methods for the estimation of insulin sensibility [31]

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Summary

Introduction

Prediabetes (PreD) refers to an intermediary phase between healthy state and diabetes disease where glycaemia is altered but still below the threshold for the diagnosis of diabetes. PreD can, itself, provoke severe complications in tissues and organs, increase microvascular and macrovascular disease, and act as a potential risk factor for type 2 diabetes (T2D) and cardiovascular diseases [1,3,4]. PreD occurrence has worryingly raised in past years, and current predictions estimate a greater global prevalence for the coming decades to the extent that it will reach epidemic proportions worldwide [1]. Current evidence indicates that diabetes prevention programs, based only on lifestyle change, have not been successful in preventing T2D in people with isolated impaired fasting glucose

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