A graded model of dietary zinc deficiency:: Effects on growth, insulin-like growth factor-1, and the glucose/insulin axis in weanling rats

Objective: Severe zinc (Zn) deficiency inhibits growth, insulin storage and release. Mild or moderate Zn deficiency may also have profound physiological effects that are not outwardly evident. We examined the effects of graded levels of low Zn intake on growth, insulin-like growth factor-I (IGF-I) and glucose homeostasis in weanling rats. Methods: Weanling rats were fed ad libitum for 3 weeks with diets containing different Zn levels: very low Zn, low Zn or mildly low Zn; there was also a control group and an additional group was pair-fed to very low Zn rats. Growth and food intake were recorded. Serum Zn, IGF-I, IGF binding protein-3 (IGFBP-3), serum insulin and glucose, tissue Zn and jejunal sucrase activity were measured. Relative liver IGF-I and IGFBP-3 mRNA levels were quantified. Results: Serum and tissue Zn were significantly lower in rats fed very low Zn (compared with pair-fed animals and controls) and low Zn (compared with controls). Growth was significantly lower in rats fed very low Zn and pair-fed animals (compared with controls) and in those fed very low Zn (compared with pair-fed animals). Liver IGF-I and IGFBP-3 mRNA levels were higher in low Zn animals compared with controls. Serum IGF-I and IGFBP-3 levels were not affected by diet. Serum glucose was significantly higher in rats fed very low Zn than in pair-fed animals (191 +/- 28 vs 99 +/- 5 mg/dL, respectively). Sucrase activity was lower in rats fed very low Zn than in pair-fed animals or controls and a linear relationship was observed between serum glucose and insulin (r = 0.65, P < 0.01) in pair-fed animals and controls but not in Zn-deficient groups. Conclusion: Severe Zn deficiency was associated with hyperglycemia and relative hypoinsulinemia. Mild degrees of Zn deficiency also altered glucose metabolism, suggesting that Zn intake may be a sensitive regulator of glucose homeostasis.