The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy

Abstract

Glucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

A review of the role of inositols in conditions of insulin dysregulation and in uncomplicated and pathological pregnancy

“…Myo-inositol treatment in the genetically-modified db/þ mouse model of GDM reduced maternal intra-abdominal, gonadal and perirenal adiposity, but had no apparent effect on fetal size (Plows et al 2017). In contrast, in a high fat diet mouse model of GDM, myo-inositol treatment did not affect maternal glycemia or fat accretion (Plows et al 2020), but did increase maternal adipose tissue mRNA expression of Ir, Irs1, Akt2, and Pck1, which are all key members of the insulin signaling pathway, and demonstrated an associated decrease in offspring birthweight (Plows et al 2020). This suggests that inositol might have a pro-insulin or an insulin-like effect in adipose tissue resulting in decreased maternal lipid mobilization and lipid transfer for fetal growth.…”

Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice

“…It is related to obesity and IR, and hyperleptinemia is frequent in HFD-fed animal models [ 53 , 91 ]. In preclinical trials, pA1c and other probiotic supplementations [ 53 , 92 , 93 ] significantly reduced circulating leptin levels, while other studies did not report significant changes [ 87 , 94 ], and evidence from human studies is weak [ 95 ]. Previously, in vitro experiments in human and animal cell lines showed that leptin induces GLP-1 production [ 96 ], which could help explain our findings.…”

Dietary supplementation of inulin alleviates metabolism disorders in gestational diabetes mellitus mice via RENT/AKT/IRS/GLUT4 pathway

“…Although women are able to maintain adequate glycemic control using these treatment strategies, they can be difficult to implement, and concerns remain regarding the long-term effects of oral agents on the developing fetus. For these reasons, it would be beneficial to develop novel, safe, and effective strategies for GDM risk reduction [ 14 ].…”