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Paulette M. Yamada, PhD Mentor: Dr. Lee Recent Work Insulin-like growth factor binding protein (IGFBP)-3 is known to regulate metabolism. The manner in which IGFBP-3 regulates metabolism is unclear as controlled experiments and epidemiological studies produce conflicting results. We created a colony of mice that lack IGFBP-3, and fed them a high fat diet. We found that mice void of IGFBP-3 had elevated blood glucose and insulin levels, initially suggesting they have poor metabolic control. However, when subjected to a large glucose dose, their metabolism performed equally well as compared to control mice. Insulin is a hormone responsible for controlling blood glucose levels. Mice lacking IGFBP-3 also had greater resting insulin levels, suggesting they have poor metabolic control. However, when subjected to large insulin dose, the metabolism of IGFBP-3 devoid mice was similar to controls. At first glace, IGFBP-3 appear to be at metabolic disadvantage at rest. However, when stressed with glucose and insulin, these mice preserve their metabolic capacity. Further testing showed that IGFBP-3 void mice had greater fat stores in the liver, but lower visceral fat. In addition, these mice had greater skeletal muscle mass. The 3 major tissues which control metabolism: fat, muscle and liver, were drastically altered in mice lacking IGFBP-3. Collectively, these data provide definitive evidence that IGFBP-3 regulates metabolism. Clinical implications include a possible role for IGFBP-3 in regulating metabolism, metabolic syndrome and type 2 diabetes. |
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