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Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a ( insra) and b ( insrb) caused \u03b2-cell hyperplasia and lethality from 5 to 16 days postfertilization (dpf) (Yang BY, Zhai G, Gong YL, Su JZ, Han D, Yin Z, Xie SQ. Sci Bull (Beijing) 62: 486\u2013492, 2017). In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively. A high-carbohydrate diet was provided for insulin receptor knockout zebrafish from 60 to 120 dpf to investigate phenotype inducement and amplification. We observed hyperglycemia in both insra\u2212\/\u2212 fish and insrb\u2212\/\u2212 fish. Impaired growth hormone signaling, increased visceral adiposity, and fatty liver were detected in insrb\u2212\/\u2212 fish, which are phenotypes similar to the lipodystrophy observed in mammals. More importantly, significantly diminished protein levels of P-PPAR\u03b1, P-STAT5, and IGF-1 were also observed in insrb\u2212\/\u2212 fish. In insra\u2212\/\u2212 fish, we observed increased protein content and decreased lipid content of the whole body. Taken together, although Insra and Insrb show overlapping roles in mediating glucose metabolism through the insulin-signaling pathway, Insrb is more prone to promoting lipid catabolism and protein synthesis through activation of the growth hormone-signaling pathway, whereas Insra primarily acts to promote lipid synthesis via glucose utilization.<\/jats:p>","DOI":"10.1152\/ajpendo.00227.2017","type":"journal-article","created":{"date-parts":[[2018,1,6]],"date-time":"2018-01-06T14:46:03Z","timestamp":1515249963000},"page":"E38-E51","source":"Crossref","is-referenced-by-count":51,"title":["Different physiological roles of insulin receptors in mediating nutrient metabolism in zebrafish"],"prefix":"10.1152","volume":"315","author":[{"given":"Bin-Yuan","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China"},{"name":"University of Chinese Academy of Sciences, 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