Modulation of insulin-like growth factor-I: a specific role for vitamin B1 (thiamine)

The aim of the present study was to determine if the impairment in growth and weight gain observed with thiamine deficiency is associated with alterations in plasma and tissue levels of insulin-like growth factor-I (IGF-I). Male rats were fed a thiamine-deficient (TD) or pair-fed a nutritionally complete (C) purified diet for either 2 or 6 weeks. There was no difference in weight gain between TD and C animals at 2 weeks. Thereafter, weight gain for the two groups diverged and was 35% lower in the TD than in C rats after 6 weeks. The blood total thiamine concentration was reduced by 76% and more than 90% at 2 and 6 weeks, respectively. Although the percent of total thiamine in the pyrophosphate form was not changed in the TD group (35 to 38%), the thiamine monophosphate (TMP) form was not detectable by 6 weeks and the percent in thiamine measured as its mononitrate (TMN) form had increased from 25% in control rats to 62% after 6 weeks on the TD diet. Plasma growth hormone levels were similarly reduced after 2 and 6 weeks (70 to 85%) on the TD diet. In TD rats, plasma IGF-I was decreased 28% (2 weeks) and 40% (6 weeks). Tissue IGF-I content of TD rats decreased at 2 and 6 wk in kidney (62% and 60%), liver (30% and 54%), muscle (21% and 52%), brain (41% and 56%), and pituitary (40% and 42%). Plasma levels of IGF binding proteins (BP-1/2, BP-3, and a small molecular weight BP [28 kDa]) of TD rats were decreased approximately 65% at 2 weeks and remained reduced at 6 weeks. The depression of the IGF system in TD at 2 weeks was not associated with changes in either plasma insulin or corticosterone concentrations; at 6 weeks, however, insulin was reduced by 30% and corticosterone increased by 90%. These results suggest a role for thiamine in the modulation of the IGF system, which is independent of changes in caloric intake and changes in the plasma concentration of insulin or corticosterone.