MODULATION OF INSULIN-LIKE GROWTH-FACTOR-I - A SPECIFIC ROLE FOR VITAMIN-B-1 (THIAMINE)

The aim of the present study was to determine if the impairment in gro wth and weight gain observed with thiamine deficiency is associated wi th alterations in plasma and tissue levels of insulin-like growth fact or-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. T here was no difference in weight gain between TD and C animals at 2 we eks. Thereafter, weight gain for the two groups diverged and was 35% l ower in the TD than in C mts after 6 weeks. The blood total thiamine c oncentration was reduced by 76% and more than 90% at 2 and 6 weeks, re spectively. Although the percent of total thiamine in the pyrophosphat e form was not changed in the TD group (35 to 38%), the thiamine monop hosphate (TMP) form was nor detectable by 6 weeks and the percent in t hiamine measured as its mononitrate (TMN) Sonn had increased from 25% in control mrs to 62% after 6 weeks on the TD diet. Plasma growth horm one levels were similarly reduced after 2 and 6 weeks (70 to 85%) on t he TD diet. In TD rats, plasma IGF-I was decreased 28% (2 weeks) and 4 0%(6 weeks). Tissue IGF-I content of To rats decreased at 2 and 6 wk i n kidney (62% and 60%), liver (30% and 54%), muscle (21% and 52%), bra in (41% and 56%), and pituitary (40% and 42%). plasma levels of IGF bi nding 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 ol corticoste rone concentrations; at 6 weeks, however, insulin was reduced by 30% a nd corticosterone increased by 90%. These results suggest a role for t hiamine in the modulation of the IGF system, which is independent of c hanges in caloric intake and changes in the plasma concentration of in sulin or corticosterone.