REGULATION OF THE INSULIN-LIKE GROWTH-FACTOR SYSTEM BY ACUTE ACIDOSIS

Many catabolic conditions are characterized by disturbances in acid-ba se balance and concomitant alterations in the insulin-like growth fact or (IGF) system. However, the influence of acidosis pet se on the vari ous components of the IGF system has not been extensively examined. Th e purpose of the present study was to determine the effect of acute me tabolic acidosis on the plasma and tissue concentrations of IGF-I and the various IGF-binding proteins (IGFBPs). Conscious unrestrained Fast ed rats were infused iv with either 0.2 N HCl or an equal volume of sa line for 4 h. The arterial blood pH decreased within 60 min after stal -ting the HCl infusion and remained lower than time-matched control va lues for the entire experimental protocol. Although the plasma IGF-I c oncentration fell gradually and was reduced by 30%, compared to time-m atched control values, GH levels were unaltered, The IGF-I content of tissues collected at the conclusion of the experiment was increased in liver (35%) and kidney (63%) and unchanged in skeletal muscle. Howeve r, whereas acidosis moderately increased IGF-I messenger RNA abundance in liver, no significant alteration in IGF-I expression was detected in kidney. Acidosis also increased the plasma levels of IGFBP-1 and -2 as well as the IGFBP-1 content of liver and kidney. In contrast, the concentration of intact IGFBP-3 was decreased in acid-infused rats, an d this reduction was associated with an increased rate of IGFBP-3 prot ease activity. Acidotic rats demonstrated unremarkable changes in the plasma concentrations of glucose and insulin, but corticosterone level s were elevated throughout the experiment. The results of the present study demonstrate that in the absence of underlying pathology, acute m etabolic acidosis decreases circulating levels of IGF-I, probably by i ncreasing renal clearance of the peptide, not by decreasing hepatic IG F-I synthesis.