Glucose intolerance in teleost fish fact or fiction

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Comparative Biochemistry and Physiology Part B 129 Ž2001. 243᎐249

Review

Glucose intolerance in teleost fish: fact or fiction? Thomas W. MoonU Department of Biology, Uni¨ ersity of Ottawa, P.O. Box 450, Stn A, Ottawa, ON, Canada K1N 6N5 Received 28 August 2000; received in revised form 30 November 2000; accepted 8 December 2000

Abstract Teleost fish are generally considered to be glucose intolerant. This mini-review examines some of the background and the possible mechanistic bases for this statement. Glucose intolerance is a clinical mammalian term meaning that a glucose load results in persistent hyperglycemia. Teleost fish show persistent hyperglycemia that is generally coincident with transient hyperinsulinemia. The fact that teleost generally have high plasma insulin compared with mammals implies insulin-deficiency is not a suitable explanation for this persistent hyperglycemia. Instead, peripheral utilization of glucose is probably the principle cause of hyperglycemia. Recent evidence for muscle insulin receptors, glucose transporters and hexokinaserglucokinase is reviewed and future experimental directions are suggested. If by altering peripheral glucose utilization fish could become more glucose tolerant, costs to the aquaculture industry may be substantially reduced. 䊚 2001 Elsevier Science Inc. All rights reserved. Keywords: Fish; Glucose intolerance; Glucose utilization; Insulin; Insulin receptors; GLUT; Hexokinase; Glucokinase; Glucose-6phosphatase; Diet

1. Introduction Teleost fishes are generally considered to be glucose intolerant. The purpose of this short review is to examine glucose tolerance in fish, discuss potential explanations that may account for intolerance, and finally present some ideas that may direct our further study within this area. The reader is directed towards reviews that have dis-

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Corresponding author. Tel.: q1-613-562-5800, ext. 6002; fax: q1-613-562-5486. E-mail address: [email protected] ŽT.W. Moon..

cussed some of these issues ŽMommsen and Plisetskaya, 1991; Wilson, 1994..

2. Glucose intolerance Glucose intolerance is a term that refers to the inability of an organism to rapidly deal with a glucose load. The consequences are persistent hyperglycemia and in many cases, reduced growth. Glucose intolerance is a clinical term used in the diagnosis of insulin-dependent diabetes mellitus ŽIDDM. and is assessed by the use of a glucose tolerance test ŽGTT.. A GTT involves administer-

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T.W. Moon r Comparati¨ e Biochemistry and Physiology Part B 129 (2001) 243᎐249

ing a bolus of glucose either orally or intravenously, and if plasma glucose values do not return to baseline within 1᎐2 h, the subject Žs human. is considered to have impaired glucose tolerance. The GTT has been used in many fish studies to test glucose tolerance and in most cases, hyperglycemia is persistent. Table 1 provides a partial list of fish species where GTT have been performed. Since the early observations of Phillips et al. Ž1948. and Falkmer Ž1961., the data consistently show that teleost fishes show persistent hyperglycemia after a glucose load. The important point noted on Table 1, however, is that the time period of hyperglycemia is species- and condition-dependent. Furuichi and

Yone Ž1981. using the same glucose dose, demonstrated that the most severe hyperglycemia occurred in the carnivorous yellow tail, and the least in the omnivorous carp. In general, the more carnivorous is the species, the longer time needed to clear a glucose load. Wilson Ž1994. has suggested that marine species are more tolerant of a glucose load than freshwater species, although other data dispute this observation ŽGarcia-Riera and Hemre, 1996a,b.. Finally, there are differences in tolerance observed between chinook salmon strains ŽMazur et al., 1992.. The conditions of the test species are also key to its glucose tolerance. Again, Furuichi and Yone Ž1981. fed a 0, 10 and 40% dextrin diet to carp,

Table 1 A partial list of teleost fish species where glucose tolerance tests have been performedc Species

Routea

Dose Žmgrkg. b

Insulin change

Palmer and Ryman, 1972 Rainbow trout

O

Harmon et al., 1991 Rainbow trout

IP

300

Blasco et al., 1996 Brown trout

IV

500

Mazur et al., 1992 Chinook salmon

O

1670

­Ž; 2.

Wilson and Poe, 1987 Channel catfish

O

1670

ND

Hyperglycemia corrected by 6 h Hyperglycemia also to fructose, maltose, sucrose and dextrin

Ottolenghi et al., 1995 Channel catfish

IV

250

ND

Hyperglycemia corrected by 11 h

Falkmer, 1961 Daddy sculphin

IM

500

ND

Hyperglycemia at least to 9 h

O

167

­Ž; 3.

Furuichi and Yone, 1981 Carp

ND

Comments

x ­Ž; 2.5.

­Ž; 2. ­Ž; 2.

Red sea bream Yellow tail

Hyperglycemia at least to 7 h Pre-spawning females ᎏ mild hyperglycemia Insulin injection ᎏ mild hyperglycemia Hyperglycemia at least to 18 h

Hyperglycemia corrected by 8 h fasting Increased hyperglycemic response Hyperglycemia at least to 36 h Strain and diet differences observed

Hyperglycemia related to diet Žapprox. 5 h for carp; longer for other species. Hyperglycemia dependent upon prior feeding with dextrin

Wright et al., 1998 Tilapia

IP

2000

ND

Hyperglycemia exceeded 6 h

Ince and Thorpe, 1974 Silver European eels

IV O

500

ND

IV ᎏ hyperglycemia corrected by 9 h O ᎏ minor hyperglycemia

a

Route indicates the method used to increase glucose content: O, oral; IV, intravenous; IM, intramuscular; IP, intraperitoneal. A dose of 1 g glucose given orally, but fish weights were not reported. c ND, not done. b

T.W. Moon r Comparati¨ e Biochemistry and Physiology Part B 129 (2001) 243᎐249

red sea bream and yellow tail; the highest dextrin content resulted in the highest hyperglycemia and lowest insulin levels. Glucose tolerance is improved in chinook salmon strains previously fed a high starch diet ŽMazur et al., 1992.. Pre-spawning female rainbow trout show a mild hyperglycemia that is short lived and pre-injecting insulin always lead to a decrease in the hyperglycemic response ŽPalmer and Ryman, 1972.. Also the route of glucose dosing alters the hyperglycemic response, at least in the European eel ŽInce and Thorpe, 1974., and the glucose concentration used in the test ŽTable 1.. Prolonged food-deprivation compared with feeding will generally extend the period of hyperglycemia ŽBlasco et al., 1996; Legate et al., 2001.. And finally, the source of starch can also affect the hyperglycemic response to a glucose load ŽHemre and Hansen, 1998.. Certainly these studies and many others indicate teleost fish clear a glucose load more slowly than mammals. This has lead a number of investigators to suggest that teleost fish are an adequate IDDM model Žsee Kelley, 1993 and below.. This idea was strengthened by the early observations of Palmer and Ryman Ž1972. that insulin injection promoted hypoglycemia in fasted rainbow trout and improved glucose tolerance when given together with glucose. As with IDDM in humans, insulin seemed to be the reason for glucose intolerance in fish. There are a number of possible explanations for glucose intolerance in fish. A simple cartoon ŽFig. 1. demonstrates these various possibilities. Basically two major possibilities exist. One is at the level of insulin concentrations in the blood. Two is the peripheral utilization of glucose which in mammals, at least, is linked to the existence of insulin receptors and glucose transporters.

3. Insulin in the blood of teleost fish The simplest explanation for the lack of glucose clearance would be a low level of blood insulin. This 51᎐58 amino acid peptide is arranged in A and B chains, linked through critical disulfide bridges. The biochemistry and physiology of this peptide in fishes has been extensively reviewed ŽMommsen and Plisetskaya, 1991; Plisetskaya, 1995.. Suffice it to say that the structure of this hormone and its receptor are well

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Fig. 1. Cartoon showing the interactions thought to occur in mammals between blood glucose and glucose uptake in the two most significant glucose-sensitive tissues Žskeletal muscle and adipose tissue. and liver. Question marks are components of the pathway that have not been confirmed in fish. Dotted lines represent the mammalian pathway between the IR and GLUT, while the dashed line is a more direct pathway that may involve changes in GLUT transcription. Neither pathway has been shown to exist in fish. GLUT, Naq-independent facilitative glucose transporter; IR-RTK, insulin receptor-receptor tyrosine kinase; GK, glucokinase; HK, hexokinase; Glu, glucose; G6-P, glucose 6-phosphate.

conserved across the vertebrates. Importantly, although glucose-stimulated insulin release has been reported in vivo and in vitro in some fish species, amino acids Žespecially arginine. are a more potent insulin secretagogue in most species Žsee Mommsen and Plisetskaya, 1991.. But even more importantly, insulin levels are in the 0.2᎐5 nM range, values that tend to be higher than found in mammals ŽMommsen and Plisetskaya, 1991.. As noted by Plisetskaya Ž1998., however, the radioimmunoassay of insulin may also detect pro-insulin, and it is not clear whether this precursor peptide has any specific physiological role in fish. Until such time that pro-insulin can be measured in a fish, all that can be said is that generally insulin levels in fish are comparable with those of mammals where blood glucose is more precisely controlled. Certainly the potency of glucose as an insulin secretagogue could be important, but as noted on Table 1, hyperglycemia generally does result in hyperinsulinemia where the hormone has been studied. The one exception is the study of Harmon et al. Ž1991. where insulin levels transiently fell. The authors showed that sommatostatin-25 levels rose with glucose challenge, and this hormone is known to decrease insulin release. Glucose does activate glucokinase

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T.W. Moon r Comparati¨ e Biochemistry and Physiology Part B 129 (2001) 243᎐249

in catfish Brockmann bodies, implicating this enzyme as a glucose sensor, just as in mammals ŽRonner, 1991.. These studies imply that fish may be a good model of non-insulin-dependent diabetes ŽWilson, 1994. rather than IDDM as previously suggested ŽKelley, 1993.. Obviously other hormones may alter plasma glucose levels in fish. This could include glucagon, glucagon-like peptide ŽGLP., insulin-like growth factor ŽIGF., growth hormone, the somatostatins, cortisol and even catecholamines. It was not the purpose of this review to examine these other hormones, but reference to them can be found in Harmon et al. Ž1991., Mommsen and Plisetskaya Ž1991., Plisetskaya Ž1995. and Navarro et al. Ž1999.. Certainly the relationship between insulin and glucagon and GLP is not as well defined as it is in mammals and in fact there may be a dissociation between these hormones ŽMommsen and Plisetskaya, 1991.. It is critical, however, that any study examining glucose tolerance must also include these other hormones. If plasma insulin levels are not critically important to plasma glucose levels, what of peripheral glucose utilization?

4. Peripheral utilization of glucose by teleost fish Resting glucose turnover rates for fish species are in general 20᎐100 times lower than values reported in mammals of equivalent body mass, consistent with their lower body temperatures and metabolic rates Žsee Weber and Zwingelstein, 1995.. Blasco et al. Ž1996. have reported that brown trout increased the rate of glucose disappearance by only 1.3-fold after an IV glucose load of 500 mgrkg that raised plasma glucose four- to five-fold and insulin levels by approximately 2.5fold. Even so, in this experiment glucose uptake by red and white muscles increased by four- and three-fold, respectively. Exercise is also known to increase glucose utilization by red skeletal muscle of trout Žsee Weber and Zwingelstein, 1995.. On a total tissue weight basis, muscle represents approximately 50% of total body weight, and must be considered to be key to the disposal of glucose from the blood in fish. Certainly it is both muscle and adipose tissue in mammals that are uniquely designed to dispose of a glucose load ŽKlip et al., 1996; Zierler, 1999.. Glucose crosses tissue membranes by carrier-

facilitative transport. There are at least five Naqindependent glucose transport isoforms in mammals, collectively called GLUT, with GLUT-1 and -4 found in skeletal muscle and adipose tissue ŽKlip et al., 1996; Zierler, 1999.. When insulin binds to its membrane receptor, GLUT-4 moves from an intracellular to a membrane position, enhancing the movement of glucose into the muscle cell Žsee Fig. 1.; GLUT-1 is thought to be constitutively expressed. Whether such a system exists in fish is not clear. Wright et al. Ž1998. were unable to detect either GLUT-1 or -4 mRNA or protein in skeletal muscle of tilapia using mammalian probes. Using the identical techniques, Legate et al. Ž2001. were also unable to demonstrate any mammalian GLUT homologue in muscle of rainbow trout, brown bullhead or American eel, even though glucose uptake into skeletal muscle membrane vesicles followed hyperbolic kinetics. However, at this conference, Planas et al. Ž2000. presented phylogenetic evidence for a GLUT-4 homologue in brown trout muscle. Whether this homologue is an insulin-dependent GLUT awaits further investigation. Insulin receptors do exist on skeletal muscle from a number of fish species. Gutierrez and ´ colleagues Žreviewed by Navarro et al., 1999. report fewer muscle insulin receptors in fish than mammals and higher receptor numbers in herbivorous than carnivorous fish species. In addition, fasting decreases and hyperinsulinemia downregulates receptor numbers Žsee Navarro et al., 1999.. Insulin binding to its receptors activates receptor tyrosine kinase, but it may be that the signaling pathway beyond the receptor differs between fish and mammals; this has yet to be studied. Certainly one of the most intriguing issues with fish is that the number of IGF-I Žinsulin-like growth factor-I. receptors exceeds those of insulin in all species examined to date ŽNavarro et al., 1999.. IGF-I receptors are linked to developmental changes, but whether IGF-I has a metabolic role is not clear. These studies demonstrate that fish skeletal muscle does express facilitative glucose transporters, possibly a mammalian GLUT homologue, and insulin receptors but whether these two systems are coupled as in mammals is unknown. GLUT-4 in null mice do show higher blood glucose and insulin values, but these differences were gender-dependent and did not

T.W. Moon r Comparati¨ e Biochemistry and Physiology Part B 129 (2001) 243᎐249

clearly demonstrate a dysfunction in glucose homeostasis ŽKatz et al., 1995.. Glucose intolerance in fish may at least partly be explained by either low activity or numbers of these transporters andror receptors, as previously suggested Žsee Navarro et al., 1999., but there are other possibilities ŽFig. 1.. Once inside the cells, glucose must be phosphorylated to glucose-6-phosphate by a hexokinase ŽHK. to ensure favorable glucose gradients for transport. Hexokinases are a family of enzymes designated HK I᎐IV or A᎐D in mammals ŽIynedjian, 1993.. These are either high ŽHK I᎐III; K m ( 0.1 mM glucose. or low ŽHK IV or glucokinase, GK; K m ) 5 mM. affinity enzymes, with GK being present in the liver and endocrine pancreas of mammals. Glucokinase expression is required for normal plasma glucose levels and insulinsecretion rates in mammals as demonstrated in a GK-transgenic mice model ŽNiswender et al., 1997.. This requirement reflects the key role that glucose plays in the mammalian liver regulating enzymes of glycolysis, gluconeogenesis and lipogenesis. Fish tissues, including muscle, express a high affinity HK ŽMoon and Foster, 1995.. Tranulis et al. Ž1996. did report hepatic GK activities in Atlantic salmon and recent studies demonstrate a carbohydrate-induced GK mRNA expression and GK activity in rainbow trout, gilthead seabream and common carp ŽPanserat et al., 2000a.. Induction is linked to increased plasma glucose values in these species, although all changes were much reduced for the omnivorous carp. Minor alterations were noted in HK activities in this study. The role of the liver in glucose tolerance is not as clear in fish as in mammals. Insulin receptors are present Žsee Navarro et al., 1999. but the existence of a GLUT has not been shown. Blasco et al. Ž1996. did report 2-deoxyglucose uptake and phosphorylation in the liver of brown trout, but rates were low reflecting what the authors assumed to be high glucose-6-phosphatase ŽG6Pase. activities. Whether brown trout have an inducible hepatic GK is not known, but this report did show that uptake and phosphorylation of glucose are well coupled. High plasma glucose should reduce hepatic glucose output in an insulin-dependent manner ŽZierler, 1999., but if not, this could exaggerate plasma glucose levels in fish receiving a glucose load. The contrary enzyme to HKrGK is G6Pase, and there is agreement in the mam-

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malian literature that the glucose-repression of this enzyme is required for normal glycemia. Interestingly, Panserat et al. Ž2000b. were unable to show glucose repression of rainbow trout G6Pase mRNA. Further studies are needed to clarify the role of the liver in teleost glucose homeostasis. Panserat et al. Ž2000a. do conclude that things other than GK must be involved as levels of this enzyme and its induction were lowest in the omnivorous carp compared with the more carnivorous species of trout and seabream, a result contrary to expectations.

5. Perspectives This short review can not answer the question ‘are teleost fish glucose intolerant’? Certainly the long held view that they are must be tempered by new data that are noted here, including speciesspecific sensitivities, existence of hepatic carbohydrate-inducible GK activities, and existence of skeletal muscle GLUT. So what research questions need to be addressed? 1. The issue of metabolic rate is overlooked in all studies of glucose intolerance. The average fish has an oxygen consumption rate one-tenth that of mammals. The implication is that blood flows, nutrient uptake, nutrient demands, etc. will scale accordingly. Certainly this is the case for glucose turnover ŽWeber and Zwingelstein, 1995., so why should teleost fish clear a glucose load as quickly as a similar sized mammal? In fact, if they did one might question why they do! Looking at tuna with their high glucose turnover and metabolic rates compared with other teleosts ŽWeber and Zwingelstein, 1995. might address this issue; a very difficult experiment indeed. 2. The presence of a muscle GLUT in fish must be confirmed. As noted above, a GLUT homologue has been identified ŽPlanas et al., 2000., but is this GLUT coupled to the insulin receptors known to exist in fish muscle? The signaling pathway between the insulin receptor and the GLUT needs to be established. There is some evidence that the linkage of GLUT to specific hexokinase isoforms in mammalian skeletal muscle may lead to insulin resistance ŽEbeling et al., 1998., and this possibility must be considered in fish.

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3. It is unlikely that insulin-deficiency is responsible for glucose intolerance, but the biologically-active insulin levels in blood need to be determined. Does pro-insulin contribute significantly to the content of insulin measured in the radioimmunoassay ŽPlisetskaya, 1998.? If so, does pro-insulin play any metabolic role? 4. Obviously other hormones may impact upon glucose tolerance. Glucagon, GLP, IGF, growth hormone, the somatostatins, cortisol and the catecholamines may all be important. As noted in the paper by Kelley et al. Ž2001., islectomy in the goby results in a diabetic-like condition after 15᎐20 days. This delay may be due to an absence of glucagon and possibly directed by cortisol. Few studies have looked at multiple hormones as the key to glucose utilization. 5. Given that hormones other than insulin may be involved, the use of glucose may also be affected by other nutrients within a diet. Diets high in carbohydrate are generally designed to be isocaloric by modifying levels of lipids and protein; might such changes affect the use of carbohydrates especially if these ‘other’ hormones alter the handling of lipids or proteins? Obviously total diet composition must to be examined to estimate nutrient interactions. 6. Does the liver play any role in fish glucose utilization? In mammals the presence of GK is key to normal glucose homeostasis ŽNiswender et al., 1997.. Is this the case for fish? Transient expression of trout embryos with human GLUT-1 and rat hexokinase II increased 3-O-methylglucose uptake and oxidation of glucose ŽKrasnov et al., 1999.. Such studies are a start to potentially addressing this issue. The issue of G6Pase also needs to be addressed to see whether the hepatic GKrG6Pase cycle is a key component to glucose intolerance. It is clear that more work is necessary especially with regards to the differences between those teleost species that can utilize high carbohydrate diets effectively compared with the carnivorous salmonids that seem to be preferred by the aquaculture industry. Molecular biology tools will greatly assist in these efforts. Enhancing the carbohydrate tolerance of species under aquacul-

ture will decrease food costs, decrease demand for fish mealroil and reduce environmental pollution resulting from high nitrogenrphosphorous meals. Each of these will have a positive impact upon the aquaculture industry and the perception of the industry by the general public.

Acknowledgements I would like to acknowledge discussions with Tom Mommsen, Kevin Kelley and Josep Planas at the 4th International Symposium on Fish Endocrinology in Seattle, WA. These discussions helped focus some of my thinking on these issues. Also, thanks to the Natural Sciences and Engineering Research Council of Canada for supporting my research program. References Blasco, J., Fernandez-Borras, J., Marimon, I., Requena, A., 1996. Plasma glucose kinetics and tissue uptake in brown trout in vivo: Effect of an intravascular glucose load. J. Comp. Physiol. B 165, 534᎐541. Ebeling, P., Koivisto, V.A., Koivisto, V., 1998. Insulinindependent glucose transport regulates insulin sensitivity. FEBS Lett. 436, 301᎐303. Falkmer, S., 1961. Experimental diabetes research in fish. Acta Endocrinol. Copenh. Suppl. 59, 1᎐122. Furuichi, M., Yone, Y., 1981. Change of blood sugar and plasma insulin levels of fishes in glucose tolerance test. Bull. Jpn. Soc. Sci. Fish. 47, 761᎐764. Garcia-Riera, M.P., Hemre, G.-I., 1996a. Glucose tolerance in turbot, Scophthalmus maximus ŽL... Aquaculture Nutr. 2, 117᎐120. Garcia-Riera, M.P., Hemre, G.-I., 1996b. Organ responses to 14 C-glucose injection in Atlantic halibut, Hippoglossus hippoglossus ŽL.., acclimated to diet of varying carbohydrate content. Aquaculture Res. 27, 565᎐571. Harmon, J.S., Eilertson, C.D., Sheridan, M.A., Plisetskaya, E.M., 1991. Insulin suppression is associated with hypersomatostatinemia and hyperglucagonemia in glucose-injected trout. Am. J. Physiol. 261, R609᎐R613. Hemre, G.-I., Hansen, T., 1998. Utilization of different dietary starch sources and tolerance to glucose loading in Atlantic salmon Ž Salmo salar ., during parrsmolt transformation. Aquaculture 161, 145᎐157. Ince, B.W., Thorpe, A., 1974. Effects of insulin and metabolite loading on blood metabolites in the European silver eel Ž Anguilla anguilla L... Gen. Comp. Endocrinol. 23, 460᎐471.

T.W. Moon r Comparati¨ e Biochemistry and Physiology Part B 129 (2001) 243᎐249

Iynedjian, P.B., 1993. Mammalian glucokinase and its gene. Biochem. J. 293, 1᎐13. Katz, E.B., Stenbit, A.E., Depinho, R., Charron, M.J., 1995. Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT-4. Nature 377, 151᎐155. Kelley, K.M., 1993. Experimental diabetes mellitus in a teleost fish. 1. Effect of complete isletectomy and subsequent hormonal treatment on metabolism in the goby, Gillichthys mirabilis. Endocrinology 132, 2689᎐2695. Kelley, K.M., Haigwood, J.T., Perez, M., Nicholson, G.S., 2001. Integrating metabolism and growth: a view from the diabetic goby. Comp. Biochem. Physiol. Žin press. Klip, A., Volchuk, A., He, L.J., Tsakiridis, T., 1996. The glucose transporters of skeletal muscle. Semin. Cell Dev. Biol. 7, 229᎐237. Krasnov, A., Pitkanen, T.I., Reinisalo, M., Molsa, ¨ ¨ ¨ H., 1999. Expression of human glucose transporter type 1 and rat hexokinase type II complementary DNAs in rainbow trout embryos: effects on glucose metabolism. Mar. Biotechnol. 1, 25᎐32. Legate, N.J., Bonen, A., Moon, T.W., 2001. Glucose tolerance and peripheral glucose utilization in the rainbow trout Ž Oncorhynchus mykiss., the American eel Ž Anguilla rostrata. and the black bullhead catfish Ž Ameiurus melas.. Gen. Comp. Endocrinol. Žin press. Mazur, C.N., Higgs, D.A., Plisetskaya, E.M., March, B.E., 1992. Utilization of dietary starch and glucose tolerance in juvenile chinook salmon Ž Oncorhynchus tshawytscha. of different strains in seawater. Fish Physiol. Biochem. 10, 303᎐313. Mommsen, T.P., Plisetskaya, E.M., 1991. Insulin in fishes and agnathans: history, structure and metabolic regulation. Rev. Aquat. Sci. 4, 225᎐259. Moon, T.W., Foster, G.D., 1995. Tissue carbohydrate metabolism, gluconeogenesis and hormonal and environmental influences. In: Hochachka, P.W., Mommsen, T.P. ŽEds.., Biochemistry and Molecular Biology of Fishes, Metabolic Biochemistry, 4. Elsevier, Amsterdam, pp. 65᎐100. Navarro, I., Leibush, B.N., Moon, T.W. et al., 1999. Insulin, insulin-like growth factor-I ŽIGF-I. and glucagon: the evolution of their receptors. Comp. Biochem. Physiol. 122B, 137᎐153. Niswender, K.D., Shiota, M., Postic, C., Cherrington, A.D., Magnuson, M.A., 1997. Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism. J. Biol. Chem. 272, 22570᎐22575. Ottolenghi, C., Puviani, A.C., Ricci, D., Brighenti, L.,

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Morsiani, E., 1995. The effect of high temperature on blood glucose level in two teleost fish Ž Ictalurus melas and Ictalurus punctatus.. Comp. Biochem. Physiol. 111A, 229᎐235. Palmer, T.N., Ryman, B.E., 1972. Studies on glucose intolerance in fish. J. Fish Biol. 4, 311᎐319. Panserat, S., Medale, F., Blin, C. et al., 2000a. Hepatic ´ glucokinase is induced by dietary carbohydrates in rainbow trout, gilthead seabream and common carp. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R1164᎐R1170. Panserat, S., Medale, F., Breque, J., Plagnes-Juan, E., ´ ` Kaushik, S., 2000b. Lack of significant long-term effect of dietary carbohydrates on glucose-6-phosphatase expression in liver of rainbow trout Ž Oncorhynchus mykiss.. J. Nutr. Biochem. 11, 22᎐29. Phillips Jr., S.N., Tunison, A.V., Brockway, D.R., 1948. Utilization of carbohydrates by trout. Fish. Res. Bull. NY 11, 1᎐44. Planas, J.V., Capilla, E., Gutierrez, J., 2000. Molecular ´ identification of a glucose transporter from fish muscle. FEBS Lett. 481, 266᎐270. Plisetskaya, E.M., 1995. Peptides of insulin and glucagon superfamilies in fish. Neth. J. Zool. 45, 181᎐188. Plisetskaya, E.M., 1998. A few of my not so favorite things about insulin and insulin-like growth factor ŽIGF.-I in fish. Comp. Biochem. Physiol. 121B, 3᎐11. Ronner, P., 1991. 2-Deoxyglucose stimulates the release of insulin and somatostatin from the perfused catfish pancreas. Gen. Comp. Endocrinol. 81, 276᎐283. Tranulis, M.K., Dregni, O., Christophersen, B., Krogdahl, A., Borrebaek, B., 1996. A glucokinase-like enzyme in the liver of Atlantic salmon Ž Salmo salar .. Comp. Biochem. Physiol. 114B, 35᎐39. Weber, J.-M., Zwingelstein, G., 1995. Circulatory substrate fluxes and their regulation. In: Hochachka, P.W., Mommsen, T.P. ŽEds.., Biochemistry and Molecular Biology of Fishes; Metabolic Biochemistry, 4. Elsevier, Amsterdam, pp. 15᎐32. Wilson, R.P., 1994. Utilization of dietary carbohydrate by fish. Aquaculture 124, 67᎐80. Wilson, R.P., Poe, W.E., 1987. Apparent inability of channel catfish to utilize dietary mono- and disaccharides as energy sources. J. Nutr. 117, 280᎐285. Wright Jr., J.R., O’Hali, W., Yang, H., Han, X.X., Bonen, A., 1998. GLUT-4 deficiency and absolute peripheral resistance to insulin in the teleost fish tilapia. Gen. Comp. Endocrinol. 111, 20᎐27. Zierler, K., 1999. Whole body glucose metabolism. Am. J. Physiol. Endocrinol. Metab. 276, E409᎐E426.