Endocrinology, Vol 132, 640-645, Copyright © 1993 by Endocrine Society

ARTICLES

Chiroinositol deficiency and insulin resistance. I. Urinary excretion rate of chiroinositol is directly associated with insulin resistance in spontaneously diabetic rhesus monkeys

HK Ortmeyer, NL Bodkin, K Lilley, J Larner and BC Hansen
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.

Previously, we demonstrated that nondiabetic insulin-resistant monkeys had reduced covalent insulin activation of muscle glycogen synthase (GS) compared to normal monkeys and that covalent insulin activation of adipose tissue GS was absent in these monkeys. Covalent insulin activation of muscle and adipose tissue GS in monkeys with impaired glucose tolerance and noninsulin-dependent diabetes (NIDDM) was also absent. As in humans, monkeys with NIDDM have a lower urinary excretion rate of chiroinositol (CI), a component of a putative mediator of insulin action, compared to normal monkeys. To determine whether the urinary excretion rate of CI was related to insulin resistance, which develops naturally in many obese rhesus monkeys, we examined the relationships between 24-h urinary CI excretion rate and 1) whole body insulin-mediated glucose disposal rates (M) and insulin-mediated changes in 2) the skeletal muscle GS activity ratio (sm delta GSAR), 3) the skeletal muscle glycogen phosphorylase activity ratio, and 4) the adipose tissue GS activity ratio (at delta GSAR) in 27 monkeys ranging from normal (n = 12) to insulin resistant (n = 8) to overtly diabetic (n = 7). The urinary CI excretion rate was significantly correlated with M (r = 0.47; P < 0.02), sm delta GSAR (r = 0.38; P < 0.05), skeletal muscle glycogen phosphorylase activity ratio (r = -0.49; P < 0.01), and at delta GSAR (r = 0.46; P < 0.02). The urinary CI excretion rate was also correlated with glucose tolerance (r = 0.39; P < 0.05). There was a wide range of urinary CI excretion rates (0.42-5.17 mumol/day) in monkeys with normal fasting plasma glucose concentrations. However, of the 7 diabetic monkeys, 6 had a urinary CI excretion rate below 2.0 mumol/day, and in the subgroup of 16 monkeys with a urinary CI excretion rate less than 2.0 mumol/day, the associations of urinary CI with M rate (r = 0.65; P < 0.005), glucose tolerance (r = 0.63; P < 0.01), and sm delta GSAR (r = 0.73; P < 0.001) increased in strength and significance. We propose that the urinary CI excretion rate may be 1) a biochemical indicator of both in vivo and in vitro insulin resistance and 2) a noninvasive diagnostic tool with potential for the identification of those individuals at risk for NIDDM and other related diseases with insulin resistance.

This article has been cited by other articles:

				P. M. Brown, T. T. Caradoc-Davies, J. M. J. Dickson, G. J. S. Cooper, K. M. Loomes, and E. N. Baker Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron oxygenase with a key role in inositol metabolism PNAS, October 10, 2006; 103(41): 15032 - 15037. [Abstract] [Full Text] [PDF]

				N. R. F. Nascimento, L. M. A. Lessa, M. R. Kerntopf, C. M. Sousa, R. S. Alves, M. G. R. Queiroz, J. Price, D. B. Heimark, J. Larner, X. Du, et al. Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide PNAS, January 3, 2006; 103(1): 218 - 223. [Abstract] [Full Text] [PDF]

				M. Horbowicz and R. L. Obendorf Fagopyritol Accumulation and Germination of Buckwheat Seeds Matured at 15, 22, and 30{degrees}C Crop Sci., May 27, 2005; 45(4): 1264 - 1270. [Abstract] [Full Text] [PDF]

				V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]

				J. M. Kawa, R. Przybylski, and C. G. Taylor Urinary chiro-Inositol and myo-Inositol Excretion Is Elevated in the Diabetic db/db Mouse and Streptozotocin Diabetic Rat Experimental Biology and Medicine, September 1, 2003; 228(8): 907 - 914. [Abstract] [Full Text] [PDF]

				J. E. Nestler, D. J. Jakubowicz, P. Reamer, R. D. Gunn, and G. Allan Ovulatory and Metabolic Effects of d-Chiro-Inositol in the Polycystic Ovary Syndrome N. Engl. J. Med., April 29, 1999; 340(17): 1314 - 1320. [Abstract] [Full Text] [PDF]