Hyperinsulinemia is closely related to low urinary clearance of D-chiro-inositol in men with a wide range of insulin sensitivity.
ABSTRACT We have previously shown that women with polycystic ovary syndrome (PCOS) have increased urinary clearance of D-chiro-inositol (uCl(DCI)), which was positively associated with hyperinsulinemia. The objective of this study was thus to determine if such relationship also exists in men with a large range of insulin sensitivity and levels. A cross-sectional study was performed on 11 brothers of women with PCOS and 21 control men. In this study, brothers served as a model of insulin resistance. We assessed uCl(DCI), urinary clearance of myo-inositol, and insulin levels with a standard 75-g oral glucose tolerance test, a 2-hour euglycemic-hyperinsulinemic clamp, and a 24-hour urine collection. Our results showed in all men together that low uCl(DCI) was strongly associated (P < .001) with hyperinsulinemia, for which uCl(DCI) was a significant predictor independent of other classic factors. Brothers were heavier than controls (P = .02), with increased glucose-stimulated glucose (P < .001) and insulin levels (P < .001) and reduced insulin sensitivity (P = .001). In this group, plasma DCI was increased by 3-fold (P = .02), with a 3-fold decrease in the uCl(DCI) to urinary clearance of myo-inositol ratio, which was almost significant (P = .07). Low uCl(DCI) is strongly associated with hyperinsulinemia in all men, and brothers of PCOS women who are more insulin resistant display increased plasma DCI and borderline decreased uCl(DCI). Thus, compensatory hyperinsulinemia might suppress renal clearance of DCI to increase plasma DCI levels and partially compensate for insulin resistance by improving DCI availability in men. The apparent discrepancy with PCOS women might be explained by higher insulin levels in men as compared with women and requires confirmation.
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ABSTRACT: Diabetes mellitus is a complex disease that is characterized by the defection of insulin sensitivity in such peripheral tissues as skeletal muscle, adipose tissue and liver. We have previously demonstrated that certain inositol derivatives stimulated glucose uptake accompanied by the translocation of glucose transporter 4 (GLUT4) to the plasma membrane in L6 myotubes. We investigated in this present study whether an oral intake of D-pinitol (PI) and myo-inositol (MI) would affect GLUT4 translocation in the skeletal muscle of mice. PI or MI at 1 g/kg BW administered orally to mice 30 min before a post-oral injection of glucose at 2 g/kg BW resulted in both PI and MI increasing GLUT4 translocation in the skeletal muscle and lowering the plasma glucose and insulin levels. PI and MI, therefore, have the potential to prevent diabetes mellitus by reducing the postprandial blood glucose level and stimulating GLUT4 translocation in the skeletal muscle.Bioscience Biotechnology and Biochemistry 05/2010; 74(5):1062-7. DOI:10.1271/bbb.90963 · 1.06 Impact Factor
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ABSTRACT: With diabetes mellitus becoming an important public health concern, insulin-delivery systems are attracting increasing interest from both scientific and technological researchers. This feature article covers the present state-of-the-art glucose-responsive insulin-delivery system (denoted as GRIDS), based on responsive polymer materials, a promising system for self-regulated insulin delivery. Three types of GRIDS are discussed, based on different fundamental mechanisms of glucose-recognition, with: a) glucose enzyme, b) glucose binding protein, and c) synthetic boronic acid as the glucose-sensitive component. At the end, a personal perspective on the major issues yet to be worked out in future research is provided.Macromolecular Bioscience 11/2013; 13(11). DOI:10.1002/mabi.201300120 · 3.85 Impact Factor
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ABSTRACT: Glucose-responsive polymer nanogels that can undergo a reversible and rapid volume phase transition in response to the fluctuation in blood glucose concentration have the potential to regulate the delivery of insulin mimicking pancreatic activity. We report here such a glucose-responsive polymer nanogel, which is made of concanavalin A (ConA) interpenetrated in a chemically crosslinked network of poly(N-isopropylacrylamide) (poly(NIPAM)). The introduction of ConA, a plant lectin protein, into the poly(NIPAM) network makes the newly developed semi-interpenetrating-structured nanogels responsive to glucose over a glucose concentration range of 0–20 mM at a physiological pH of 7.4. While the nanogels can swell and become stable shortly (<1 s) after adding glucose over a concentration range of 50.0 μM to 20.0 mM, the changes in the average hydrodynamic radius and the size distribution of the nanogels can be fully reversible within the experimental error even after ten cycles of adding/removing glucose. The association rate constant is determined to be ca. 1.8 mM−1 s−1, and the dissociation rate constant is ca. 7.5 s−1, indicating a fast reversible time response to the glucose concentration change of the nanogels. Moreover, in vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations.11/2013; 5(1). DOI:10.1039/C3PY00778B