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.

Inositol is a naturally occurring sugar-alcohol present in plants and animals, either in its free form, as a phospholipid component or as inositol phosphate (IP) esters. Dietary inositol is readily absorbed from the intestine via SMIT1 with levels being detectable in the blood as well as in various tissues. Recent studies have revealed a potential link between free inositol content and improved growth response in animals. There is limited data suggesting why an increase in inositol would result in improved growth; however, it would appear that inositol has numerous biological functions within the body. A number of tissues are capable of synthesising this polyol from glucose, although the kidney appears to be the primary site of catabolism. Studies investigating the effect of inositol deficiencies in various animal species have revealed a number of biological processes that are reliant on inositol to function. One of inositol's main functions appears to be its involvement as a phospholipid component of cell membranes and lipoproteins. Cell signalling pathways involving phosphoinositide phospholipids, such as the IP3/DAG and IGF/PIK/Akt pathways, lead to a number of cellular responses that are important for cell survival and growth. On a larger scale, inositol appears to be essential for both prenatal and postnatal development of peripheral nerves, CNS and bone. With regards to a potential growth response, upregulation of specific signalling pathways, such as the IGF/Akt/mTOR pathway, in the skeletal muscle has been shown in response to phytase supplementation and the consequential increase in free inositol. These signalling pathways are responsible for protein synthesis and increased glucose absorption in this tissue. Since inositol has also been shown to be an important regulator of the transport and deposition of fat, it may be possible to use inositol to support the growth of a lean animal.

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

Phytases have been used commercially since the early 1990s and have been the focus of considerable and sustained research for many decades. Despite this heroic effort there are still areas of persistent uncertainty such as the obscurity surrounding total compared with digestible calcium, appropriate modification to dietary sodium (and other electrolyte) concentrations, the usefulness of the amino acid and energy digestibility improvements and ultimately the effect of phytase on nutrient requirement. One further area which has attracted some attention recently is the effect of unconventionally high doses of phytase (i.e. >2,500 FTU/kg from Aspergillus niger or Escherichia coli) in an attempt to ostensibly ‘de-phytinise’ the diet. The effects of such ‘super’ doses of phytase can be considerable, and often beyond that which may be reasonably expected based on improvement in P digestibility per se. This review article addresses these effects and suggests mechanisms by which they may be explained.

The phosphoinositide (PI) intracellular signaling pathway, which triggers Ca2+ release from intracellular stores, appears to be a central feature of phototransduction in most invertebrate species studied. Procedures designed to inhibit PI-pathway reactions cause suppression of excitation to dim lights. However, in Limulus photoreceptors, responses to bright stimuli are in fact enhanced by some of these procedures, suggesting that PI metabolism is not obligatory for light-induced excitation. Other studies, however, suggest that Ca2+ release is obligatory for excitation. We studied this issue by examining the effects of PI-pathway inhibitor, Li+, on electrophysiological responses to light in Limulus photoreceptors. Li+ is reported to cause depletion of intracellular PI-pathway intermediate, inositol; and it offers the pharmacological advantage that its block can be bypassed by introducing exogenous inositol. Introduction of Li+ caused a very slowly developing but complete suppression of responses to dim stimuli. In contrast, Li+ caused a rapidly developing but partial suppression of responses to bright stimuli. Li+-induced suppression was reversed by exogenous introduction of inositol. In addition, inositol prevented Li+-induced suppression of excitation. Li+ enhanced light adaptation (light-induced desensitization) but slowed response deactivation, indicating a difference in the processes underlying these phenomena. Li+ slowed dark adaptation, the recovery of sensitivity following light adaptation. All of these effects were prevented or rescued by extracellularly applied inositol, suggesting the presence of a transmembrane inositol transport system. The overall results suggest that PI-dependent signaling is central and obligatory for excitation in Limulus, at least for responses to dim to moderate illumination. The failure of Li+ to suppress bright light-induced excitation completely may be due to a failure of Li+ to block PI metabolism completely, as in other systems; however, it may point to a parallel, PI-independent excitation pathway possessing very low light sensitivity when PI metabolism is inhibited.