d- chiro-Inositol is absorbed but not synthesised in rodents

Abstract

d-chiro-inositol (DCI) and pinitol (1d-3-O-methyl-chiro-inositol) are distinctive inositols reported to possess insulin-mimetic properties. DCI-containing compounds are abundant in common laboratory animal feed. By GC-MS of 6 m-HCl hydrolysates, Purina Laboratory Rodent Diet 5001 (diet 5001) contained 0.23 % total DCI by weight with most found in the lucerne and soya meal components. In contrast, only traces of l-chiro-inositol were observed. The DCI moiety was present in a water-soluble non-ionic form of which most was shown to be pinitol. To measure the absorption of dietary inositols, rats were fed diet 5001 in a balance study or given purified pinitol or [2H6]DCI. More than 98 % of the total DCI fed to rats as diet 5001, purified pinitol or [2H6]DCI was absorbed from the gastrointestinal tract. Rats chronically on diet 5001 consumed 921 mumol total DCI/kg body weight per d but excreted less than 5.3 % in the stools and urine, suggesting that the bulk was metabolised. The levels of pinitol or DCI in plasma, stools or urine remained relatively stable in mice fed Purina PicoLab Rodent Diet 20 5053 over a 5-week period, whereas these values declined to very low levels in mice fed a pinitol/DCI-deficient chemically defined diet. To test whether DCI was synthesised or converted from myo-inositol, mice were treated with heavy water or [2H6]myo-inositol. DCI was neither synthesised endogenously from 2H-labelled water nor converted from [2H6]myo-inositol. DCI and pinitol in rodents appear to be derived solely from the diet.

Fig. 1

Structures of inositols: d-chiro-inositol (DCI); pinitol; and myo-inositol. DCI is numbered as recommended by the International Union of Pure and Applied Chemistry⁽³⁴⁾. Pinitol and myo-inositol according to the convention for DCI.

Fig. 2

Food intakes (panel A) and body weights (B) of mice fed Purina PicoLab® Rodent Diet 20 5053 (diet 5053) (solid black circles) or pinitol/DCI-deficient Diet (empty circles). Male C57BL/6J mice (n=8 for each diet) were fed 5053 or pinitol/DCI-deficient diet for 5 weeks. Food intake was measured twice a week and their average represents weekly food intake (g/day). Body weight was determined at the beginning and once a week. Effects of diet (P=0.0002), time (P<0.0001), and interactions between time and diet (P<0.0001) were statistically significant. The levels of statistical differences between 5053 and the pinitol/DCI-deficient diet at each time point are indicated by **P < 0.001.

Fig. 3

Plasma, stool, or urine inositols over time in mice fed Purina PicoLab® Rodent Diet 20 5053 (5053) (solid black circles) or Pinitol/DCI-deficient Diet (empty circles). Male C57BL/6J (n=8 for each diet) were fed 5053 or Pinitol/DCI-deficient diet for 5 weeks. Blood, urine, and stool were obtained at 0, 1, 2, and 5 weeks. Pinitol (Left panel: A. plasma; B. stool; C. urine) or DCI (right panel: A. plasma; B. stool; C. urine) was analyzed as described in Materials and Methods. The levels of statistical differences between 5053 and the pinitol/DCI-deficient diet at each time point are indicated by **P < 0.001.