Characterization of urinary inositol excretion in diabetes mellitus and the antihyperglycemic effects of a buckwheat concentrate, containing D-chiro-inositol

Diabetes mellitus (DM) is a chronic disease and a leading cause of death in developed countries. DM is characterized by hyperglycemia, resulting from deficiencies in insulin secretion and levels and/or inadequate insulin action. Insulin mimetic compounds, containing D-chiro-inositol (D-CI) and myo-inositol (MI), have been identified as having altered bioactivity and metabolism in DM. The pattern of urinary excretion of D-CI and MI has also been reported as altered in DM, however, there are discrepancies regarding the direction of the change. In addition, administration of chemically synthesized free D-CI has demonstrated antihyperglycemic effects in DM, presumably in response to a correction of the altered activity and metabolism of these compounds. Buckwheat contains D-CI, MI, and derivatives of D-CI known as fagopyritols, and is a potential natural source of these compounds in treating DM. The present research investigated (1) the pattern of urinary D-CI and MI excretion in animal models and humans with DM, (2) the effects of a buckwheat concentrate (BWC) containing D-CI, MI, and fagopyritols on in vivo glycemic control, (3) the insulin-mimetic effects of the BWC on cell signal transduction proteins in H4IIE cells, and (4) the effects of a BWC on glucose uptake in H4IIE cells. The main findings of this research were that (1) urinary excretion of D-CI and MI was elevated in animal models and humans with DM, concomitant with hyperglycemia and glucosuria, (2) a BWC, containing D-CI, MI, and fagopyritols, had antihyperglycemic effects in an animal model of DM, (3) the BWC demonstrated insulin-mimetic effects by activating MAPK and p70S6K (Thr421) in H4IIE cells, and (4) the BWC inhibited basal and insulin-stimulated glucose uptake in H4IIE cells, whereas D-CI stimulated glucose uptake similar to insulin in these cells. Thus, elevated urinary D-CI and MI excretion is associated with hyperglycemia and glucosuria. This finding can contribute to the current understanding of DM and may be useful as a biomarker or lead to novel treatments for the disease. Although the components responsible are not known, the anti-diabetic properties of buckwheat suggest it may be useful in the management of DM which can have implications for the buckwheat industry.*; *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Microsoft Office.