Development of a Hyperglycemic Fish Model and Analysis of Bone Metabolism

Abstract

The high plasma glucose induced in glucose metabolism disorders leads to secondary pathologies, including bone disease. Fish scales, similar to mammalian bone, are composed of osteoblasts, osteoclasts, and calcified bone matrix and have been used as a system to analyze hyperglycemia-induced bone abnormalities. Here, we developed a hyperglycemia model in fish to study abnormalities in bone metabolism linked to increased plasma glucose and to analyze the function of calcitonin, the suppressor of osteoclastic activity, while maintaining high glucose levels. Following a 1-d fast and exposure to 5% glucose, plasma glucose concentrations increased significantly. We then examined plasma calcium and osteoclast activity of scales related to bone metabolism in goldfish treated with glucose for 5 d after a 1-d fast. The results showed that glucose treatment significantly increased plasma calcium levels at 3 and 5 d with a decrease in calcium content in the scales of goldfish. Hyperglycemia in glucose-exposed goldfish induced osteoclastic activation in scales, as indicated by the ratio of the osteoclastic activating factor (rankl) to the osteoclast inhibiting factor (osteoprotegerin, opg). Plasma calcitonin was found to be increased in glucose-exposed goldfish, which appears to suppress bone resorption by regulating the rankl/opg ratio. This hyperglycemia model, capable of examining both glucose and bone metabolism, would be valuable for analyzing the mechanism underlying abnormal bone metabolism caused by hyperglycemia.