GLUT-4 DEFICIENCY AND SEVERE PERIPHERAL RESISTANCE TO INSULIN IN THE TELEOST FISH TILAPIA

Teleost fish, in general, are glucose intolerant; this trait has been attributed to piscine islets secreting insulin primarily in response t o amino acid secretogogues rather than glucose. However, pancreatic is lets from the teleost fish tilapia, when transplanted into diabetic nu de mice, were glucose responsive even though tilapia were severely glu cose intolerant. This suggested a strong peripheral resistance to the glucostatic effects of insulin. Using Western blotting with polyclonal antibodies as well as Northern analysis for mRNA, tilapia tissues wer e found to be devoid of GLUT-LC, the insulin-sensitive glucose transpo rter responsible for the hypoglycemic effect of insulin in mammals. Th e absence of GLUT-4 in peripheral tissues may explain why tilapia, and possibly other teleost fish, are severely glucose intolerant. This su ggests that tilapia islets have evolved along mammalian lines to be gl ucose sensitive while tilapia peripheral tissue have diverged widely. Using the same methods, tilapia were found to have a very limited tiss ue distribution of the insulin-independent glucose transporter, GLUT-1 , which is responsible for basal glucose transport in mammalian cells. It is suggested that tilapia provide a naturally occurring GLUT-4 kno ckout model. (C) 1998 Academic Press.