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 primary in response to amino acid secretogogues rather than glucose. However, pancreatic islet from the teleost fish tilapia, when transplanted into diabetic nude mice, were glucose responsive even though tilapia were severely glucose 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 were found to be devoid of GLUT-4, the insulin-sensitive glucose transporter responsible for the hypoglycemic effect of insulin in mammals. The absence of GLUT-4 in peripheral tissues may explain why tilapia, and possibly other teleost fish, are severely glucose intolerant. This suggests that tilapia islets have evolved along mammalian lines to be glucose sensitive while tilapia peripheral tissue have diverged widely. Using the same methods, tilapia were found to have a very limited tissue 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 knockout model.
Wright
J R
JR
Department of Pathology, Isaak Walton Killam-Grace Health Centre for Children, Women and Families, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada. jwright@iwkgrace.ns.ca
O'Hali
W
W
Yang
H
H
Han
X X
XX
Bonen
A
A
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D001923:Brain Chemistry; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007333:Insulin Resistance; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009004:Monosaccharide Transport Proteins / Q000032:analysis* / Q000235:genetics; D009124:Muscle Proteins; D009132:Muscles / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017210:Tilapia; D014183:Transplantation, Heterologous
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat