© 2000 by The Society for Integrative and Comparative Biology
Fish Insulin, IGF-I and IGF-II Receptors: A Phylogenetic Approach1
1 Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028 Barcelona, Spain
 |
SYNOPSIS |
|---|
TOP
 SYNOPSIS INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
In fish, the structural and functional characteristics of insulin and IGF-I receptors have been well studied. Current evidence indicates that all gnatostome animals, from fish to mammals, contain separate insulin and IGF-I molecules and specific receptors for insulin and IGF-I. However, qualitative differences in the functional aspects of insulin and IGF-I receptors among vertebrate species can account for variations in the biological activity of insulin and IGF-I. In this paper we will focus on the functional evolution of the insulin and IGF-I receptors in vertebrates and on the appearance of the unrelated IGF-II receptors.
|
INTRODUCTION |
|---|
|
TOP
SYNOPSISINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
Insulin and insulin-like growth factors I and II (IGF-I and IGF-II) are peptides that belong to the same family of proteins. Insulin, IGF-I and IGF-II are structurally similar and have derived from a common ancestral molecule through a series of gene duplications and point mutations. The amino acid sequences of insulin, IGF-I and IGF-II from all vertebrate groups are currently known and a high degree of similarity is observed for each hormone among the different vertebrates (Chan et al., 1993
; Reinecke and Collet, 1998). Therefore, the primary structures of insulin, IGF-I and IGF-II have been well conserved during evolution.
Insulin and IGFs are hormones that are important for the regulation of several physiological processes, such as metabolism, growth and differentiation. In mammals, insulin is primarily involved in the regulation of carbohydrate metabolism, whereas IGF-I and IGF-II are primarily involved in the regulation of growth, cell differentiation and fetal development. Insulin and IGFs exert their effects on the cell through their binding to specific receptors anchored in the plasma membrane. In mammals, distinct and specific insulin, IGF-I and IGF-II receptors have been described. These receptors are able to recognize and discriminate, within physiological concentration of the ligands, the various members of the insulin/IGF-I family. However, a certain cross-interaction between ligands and receptors occurs. This is most evident with IGF-II, which exerts its mitogenic actions, not through its own receptor, but through the insulin and IGF-I receptors (Adashi et al., 1990; Morrione et al., 1997). It appears that the IGF-II receptor in mammals binds IGF-II to clear it from the circulation and thus regulate the levels of IGF-II reaching the target tissues (Stewart and Rotwein, 1996). Therefore, it appears that in view of the high structural similarities among insulin, IGF-I and IGF-II, the specificity of their actions is determined by the receptors.
Fish also have insulin and IGF-I receptors that will mediate the actions of insulin and IGF-I (Gutiérrez and Plisetskaya, 1991; Gutiérrez et al., 1993; Drakenberg et al., 1993). The binding properties of these receptors in different tissues and in different species of fish have been well studied and, despite their structural similarities with mammalian insulin and IGF-I receptors, show somewhat different binding characteristics than their mammalian counterparts (Párrizas et al., 1995a, b). Therefore, these differences in receptor binding between fish and mammals could explain the fact that the effects of insulin and IGF-I on metabolism and growth are less differentiated in fish than in mammals. Clearly, throughout vertebrate evolution, changes in the hormones in the insulin/IGF-I family have taken place in parallel with changes in their receptors, probably resulting in novel functions.
|
METHODS |
|---|
|
TOP
SYNOPSISINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
Receptor preparation.
Tissue homogenates were solubilized with Triton X-100 (2% final, 1 hour, 4°C), ultracentrifuged (150,000 g, 90 min, 4°C) and the supernatants (solubilized membranes) were subjected to wheat germ agglutinin (WGA) affinity chromatography to yield semipurified receptors (Párrizas et al., 1994b
). For purification of IGF-II/M6P receptors, solubilized membranes were subjected to M6P-affinity chromatography.
Binding assays.
Aliquots of the WGA or M6P eluates were incubated with increasing concentrations of cold hormone and the radiolabeled ligand (human recombinant) as a tracer for 16 hr at 4°C. The validity of the use of human ligands in fish binding assays has been previously demonstrated (Gutiérrez and Plisetskaya, 1991; Leibush et al., 1996). Semipurified receptors were precipitated with bovine-
-globulin (0.08%) and polyethylene glycol (10.4%), centrifuged (14,000 g, 5 min) and the radioactivity in the pellet was counted (Párrizas et al., 1994b).
Tyrosine kinase activity.
Aliquots of the WGA or M6P eluates were preincubated with the cold hormone for 16 hr at 4°C and were subsequently incubated with [32P]-ATP for 10 min to allow autophosphorylation. A synthetic substrate was added and incubated with the mixture for a further 30 min. Subsequently, the reaction was stopped and acid-precipitable counts were determined (Párrizas et al., 1994b).
Cross-linking of receptors.
Aliquots from WGA or M6P eluates were incubated overnight at 4°C with or without cold hormone and labeled hormone. Subsequently, samples were cross-linked with DSS, subjected to SDS-PAGE under reducing conditions and autoradiography (Gutiérrez et al., 1995; Maestro et al., 1997a).
|
RESULTS |
|---|
|
TOP
SYNOPSISINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
Structural characteristics of fish insulin and IGF-I receptors
The piscine insulin and IGF-I receptors, like their mammalian counterparts, are heterotetrameric proteins consisting of two extracellular
subunits and two membrane-anchored ß subunits, which are linked by disulfide bonds to form ß-ß heterotetramers (Drakenberg et al., 1993, Maestro et al., 1997a). The subunits of the fish insulin and IGF-I receptors have a molecular weight of approximately 115 kDa, slightly lower than the mammalian receptors, and contain the ligand binding site (Fig. 1A). The ß subunits of the fish insulin and IGF-I receptors have a molecular weight of approximately 95 kDa and contain the transmembrane domain and the intracellular tyrosine kinase domain (Fig. 1B). The existence of a certain degree of variation between the apparent molecular weight of fish and mammalian and ß subunits has been attributed to differences in glycosylation.
|
Binding characteristics of insulin and IGF-I receptors
Studies in several fish species have indicated the presence of specific insulin receptors. The number of insulin receptors in skeletal muscle of fish, however, is significantly lower than in mammals (Fig. 2). In skeletal muscle, significant differences in insulin binding have been observed among different species of fish, according to the diet habits of the species. Omnivorous and herbivorous species (e.g., carp and tilapia) show higher specific binding of insulin in skeletal muscle than carnivorous species (e.g., trout, sea bass and sea bream). It is remarkable that all fish species clearly show lower values of specific binding for insulin in skeletal muscle than rat. These binding differences among the various fish species and rat are attributed to differences in number of receptors.
|
In fish, the number of insulin receptors is not fixed and it can be regulated under different physiological situations. The specific binding of insulin in fish skeletal muscle has been found to increase after diet administration or experimental treatments. For example, administration of arginine (Fig. 3A, B), a potent insulin secretagogue in fish, food administration (Fig. 3A) or high-carbohydrate containing diets (Fig. 3B) increase the specific binding of insulin in fish skeletal muscle (Fig. 2). This up-regulation of insulin binding is due to an actual increase in the number of insulin receptors in the tissue. Although not shown here, increases in receptor number are accompanied by increases in insulin circulating levels.
|
When studies were conducted to study the binding of IGF-I in fish tissues it was found that IGF-I binding is significantly higher than insulin binding (Figs. 4, 5). It was also found that fish IGF-I receptors are more specific than insulin receptors, as shown by cross-displacement experiments. In all fish tissues examined to date, the concentration of cold IGF-I needed to displace 50% of the labeled insulin bound to the insulin receptors (EC50) is lower than the concentration of cold insulin needed to displace 50% of the labeled IGF-I bound to the IGF-I receptor. These results indicate that the cross-interaction of insulin with IGF-I receptors is less important than that of IGF-I with insulin receptors (Table 1).
|
|
|
This high and specific IGF-I binding, due to a high number of IGF-I receptors, has been found in skeletal muscle of all fish species examined (Fig. 4) and also in all fish tissues examined (Fig. 5). Even in fish tissues such as skeletal muscle and adipose tissue (Planas et al., 2000
), two well-known tissue targets of insulin in mammals, IGF-I receptors appear to be more abundant than insulin receptors. Of all tissues examined in fish, heart and brain contain the highest number of IGF-I receptors. When we examine the number of insulin and IGF-I receptors in skeletal muscle of different vertebrate species (e.g., fish, amphibians, reptiles, birds and mammals) we observe that all ectothermic animals have higher numbers of IGF-I receptors than insulin receptors (Table 2). However, endothermic animals (birds and mammals) have higher numbers of insulin receptors than IGF-I receptors. Therefore, ectothermic and endothermic vertebrates have a different ratio of insulin/IGF-I receptor numbers. We can also observe a gradual increase in the number of insulin and IGF-I receptors as we move upward in the vertebrate scale.
|
Binding characteristics of fish IGF-II receptors
In addition to the presence of specific insulin and IGF-I receptors, fish also have specific IGF-II receptors. In trout yolk sac larvae, IGF-II binding is high, even more prominent than insulin and IGF-I binding (Fig. 6). However, the high IGF-II binding in semipurified receptor preparations of trout larvae has been shown to be primarily due to the binding of IGF-II to the IGF-I receptors present in the preparations. When the IGF-II receptors are purified with manose-6-phosphate affinity chromatography to near homogeneity, the presence of a small number of specific IGF-II receptors with high affinity can be demonstrated (Fig. 7).
|
|
Functional characteristics of fish insulin and IGF-I receptors
As in mammals, the ß subunits of fish insulin and IGF-I receptors undergo autophosphorylation upon binding of the ligand to the
subunits and can subsequently phosphorylate specific substrates. Fish insulin and IGF-I receptors undergo autophosphorylation in a concentration dependent manner. In addition, activation of fish insulin and IGF-I receptors by binding of their ligands results in an activation of their tyrosine kinase domains, as measured by their ability to phosphorylate exogenous substrates (e.g., poly Glu:Tyr; 4:1). Tyrosine kinase activity induced by insulin and IGF-I appears to be similar in skeletal muscle of several species of fish, when expressed as percentage of basal activity (Table 3). However, when tyrosine kinase activity is expressed as pmol of phosphorous incorporated per fmol of receptors, the tyrosine kinase activity induced by insulin is higher than that induced by IGF-I (Table 4). This indicates that fish skeletal muscle insulin receptors, although less abundant, are more active than IGF-I receptors. Interestingly, insulin and, to a lesser extent, IGF-I stimulate tyrosine kinase activity in rat skeletal muscle several fold-higher than in fish skeletal muscle. These results indicate that insulin receptors and IGF-I receptors, to a lesser extent, in fish skeletal muscle are less active than their mammalian counterparts.
|
|
|
DISCUSSION |
|---|
|
TOP
SYNOPSISINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
Fish insulin and IGF-I receptors are heterotetrameric proteins consisting of two extracellular
subunits containing the ligand binding site, which are linked by disulfide bridges to two membrane anchored ß subunits containing the tyrosine kinase domain (Drakenberg et al., 1993; Lappova and Leibush, 1995; Maestro et al., 1997a). In addition to the structural similarity to mammalian insulin and IGF-I receptors, fish insulin and IGF-I receptors have been recently shown to have a high degree of sequence similarity to their mammalian counterparts. In particular, the partial cDNA sequences of putative fish insulin and IGF-I receptors show close identity (higher than 80%) to the human insulin and IGF-I receptors (Chan et al., 1997). Furthermore, fish insulin and IGF-I receptors show functional similarities with other vertebrate insulin and IGF-I receptors in that they are able to undergo autophosphorylation and to phosphorylate exogenous substrates. However, important differences in ligand-activated tyrosine kinase activity exist between fish insulin and IGF-I receptors and other vertebrate receptors.
From the initial studies on insulin binding to fish tissues it became apparent that fish tissues contain a relatively low number of insulin receptors, particularly when compared to mammalian tissues (Gutiérrez and Plisetskaya, 1991). Since one of the known actions of insulin is to stimulate the uptake of glucose, the low number of insulin receptors in fish tissues may partially explain the known poor utilization of carbohydrates by fish tissues (Palmer and Ryman, 1972; Cowey and Walton, 1989). Examination of the number of insulin receptors in fish skeletal muscle also revealed differences among fish species with different feeding preferences (Párrizas et al., 1994b; Párrizas et al., 1995b). In fact, carnivorous species (e.g., salmonids, sea bass, etc.) have lower numbers of insulin receptors than either herbivorous (e.g., tilapia) or omnivorous (e.g., carp) species. Therefore, the number of insulin receptors may reflect the carbohydrate content of the natural diet and could even be suggestive of a different involvement of insulin in the regulation of protein or carbohydrate metabolism in different species. In salmonids, a carnivorous group whose diet consists mainly of protein, the low number of insulin receptors in skeletal muscle probably contributes to the slow return of postprandial glucose levels in the blood to basal levels (Cowey and Walton, 1989). On the other hand, in cyprinids, an omnivorous group whose diet contains a higher percentage of carbohydrates, the higher number of insulin receptors in skeletal muscle induces a faster transition from postprandial glucose levels to basal (resting) levels. The number of insulin receptors in fish muscle tissues is regulated by the nutritional status so that it can be altered according to the physiological need. Typically, the low number of insulin receptors in fish tissues is increased (up-regulated) after circumstances which lead to increases in the circulating levels of insulin (e.g., food intake, injection of insulin secretagogues, etc.) in order to increase the tissue response to insulin (Párrizas et al., 1994a).
In addition to insulin receptors, fish tissues have been found to contain abundant IGF-I receptors (Drakenberg et al., 1993; Gutiérrez et al., 1993). In particular, specific IGF-I receptors have been detected in fish skeletal muscle (Párrizas et al., 1995b), heart (Gutiérrez et al., 1995; Párrizas et al., 1995b), brain (Leibush et al., 1996), ovary (Gutiérrez et al., 1993; Maestro et al., 1997a, b), adipose tissue (Planas et al., 2000) and testis (LeGac et al., 1995). In all the fish species examined, IGF-I receptors are more abundant than insulin receptors, independently of their feeding preference (Párrizas et al., 1995a, b). IGF-I receptors are also more abundant than insulin receptors in all fish tissues examined (Gutiérrez et al., 1995; Maestro et al., 1997a; Leibush et al., 1996). Furthermore, fish IGF-I receptors show a higher degree of specificity than fish insulin receptors (Gutiérrez et al., 1993; Gutiérrez et al., 1995; Leibush et al., 1996). Similar to the insulin receptors, the number of IGF-I receptors in white skeletal muscle is up-regulated when the circulating levels of IGF-I are elevated, such as after feeding. Therefore, fish insulin and IGF-I receptors share several important characteristics. First, both receptors are structurally similar. Second, fish insulin and IGF-I receptors appear to be physiologically regulated in a similar manner, undergoing changes in receptor number according to the physiological need. However, fish insulin and IGF-I receptors also have important differences, mainly those regarding receptor specificity and abundance.
While noticing that fish already contain separate specific receptors for insulin and IGF-I, an interesting change in skeletal and cardiac muscle insulin and IGF-I receptor numbers has been detected along the vertebrate phylogenetic scale. In fish, amphibians and reptiles, the number of insulin receptors is lower than the number of IGF-I receptors (Hainaut et al., 1991; Janicot et al., 1991; Párrizas et al., 1995a). However, in birds and mammals, the number of insulin receptors is higher than that of IGF-I receptors (Amstrong and Hogg, 1992; Dardevet et al., 1994). Therefore, it appears that the ratio between insulin and IGF-I receptors has increased during vertebrate evolution. The higher number of insulin receptors in homeothermic vertebrates is probably related to the higher physiological response of skeletal muscle to insulin in these species. Coupled with the change in insulin and IGF-I receptor numbers throughout evolution, changes in tyrosine kinase activity of the insulin and IGF-I receptors have also occurred. A significant increase in tyrosine kinase activity associated with the insulin and IGF-I receptors in skeletal muscle has been detected between ectothermic and endothermic vertebrates (Párrizas et al., 1995a). The increase in the insulin and IGF-I-stimulated tyrosine kinase activity during the course of vertebrate evolution appears to have occurred in parallel with the increase in the number of insulin and IGF-I receptors. The relative activity of the insulin and IGF-I receptor-associated tyrosine kinase has also changed during the course of vertebrate evolution. In ectothermic vertebrates, the tyrosine kinase activity associated with the IGF-I receptor, when expressed as percentage of basal activity, appears to be higher than that associated with the insulin receptor. However, when the tyrosine kinase activity is expressed as the amount of phosphorous incorporated in an exogenous substrate per amount of receptor and per unit of time, the tyrosine kinase activity associated with the insulin receptor is higher than that associated with the IGF-I receptor. It appears that the tyrosine kinase activity associated with the IGF-I receptor, if not corrected for the actual amount of IGF-I receptor present, is overestimated mainly because of the higher number of IGF-I receptors. On the other hand, in endothermic vertebrates, the tyrosine kinase activity associated with the insulin receptor is higher than that associated with the IGF-I receptor. Thus, the increase in the number of insulin receptors in skeletal muscle during the course of vertebrate evolution is accompanied by an increase in their tyrosine kinase activity (Fig. 8). These findings point towards an increase in the physiological role of insulin during vertebrate evolution. The tyrosine kinase activity associated with the IGF-I receptor has also increased during vertebrate evolution, despite being lower than that associated with the insulin receptor in homeothermic vertebrates.
|
Contrary to the presence of insulin and IGF-I receptors in all vertebrate groups, specific receptors for IGF-II have only been described in mammalian species. The IGF-II receptor is a single chain transmembrane protein that lacks a tyrosine kinase domain and, in addition to binding mannose-6-phosphate (M6P), binds IGF-II with high affinity, IGF-I with less affinity, but not insulin (Morgan et al., 1987
; Klies et al., 1988; MacDonald et al., 1988). This receptor is also known as the M6P-IGF-II receptor and it has been identified in mammals, birds and amphibians, although only the mammalian receptor has been found to contain an IGF-II binding site. Its function has been suggested to be the clearance of IGF-II from the circulation (Stewart and Rotwein, 1996). The mammalian IGF-II receptor is detected mainly during the fetal or neonatal period, with low numbers detected in the adult animal. Its exact function during development is not yet known but it is possible that this receptor allows for specific effects during embryonic and larval stages. Our group has detected the presence of a reduced number of specific IGF-II receptors in fish embryos, providing the first indication for the presence of specific IGF-II receptors in non-mammalian vertebrates (unpublished data, E.M.). Furthermore, no tyrosine kinase activity has been found to be associated with the IGF-II receptor, which supports the idea that fish and mammalian IGF-II receptors are structurally similar. Further studies are currently being conducted to determine the functional characteristics of fish IGF-II receptors.
One aspect of great interest for comparative endocrinology is the evolutionary changes that have taken place to create the complex insulin and insulin-like growth factor superfamilies that exist at the present time along the vertebrate phyla. During the course of vertebrate evolution, there must have been parallel, but not necessarily simultaneous, changes in the primary structure of both the ligands (insulin and IGF-I) and the receptors (insulin, IGF-I and IGF-II receptors). The high sequence homology of the ligands and their receptors from different vertebrate species, from agnathans to mammals, supports this notion. At one end of the vertebrate spectrum we have the hagfish, which produces insulin and an insulin-like growth factor molecule equally similar to IGF-I and IGF-II (Nagamatsu et al., 1991). More recently, it has been demonstrated that the hagfish expresses insulin receptors and IGF-I receptors (Pashmforoush et al., 1996). In elasmobranchs, evolutionarily situated between agnathans and fish, separate IGF-I and IGF-II molecules are found (Duguay et al., 1995) but no information about the receptors for these molecules is available. At the other end of the vertebrate spectrum we have the mammals, which have separate insulin, IGF-I and IGF-II molecules and separate insulin, IGF-I and IGF-II receptors. It has been hypothesized that insulin and an insulin-like growth factor molecule, such as those found in hagfish (Nagamatsu et al., 1991), diverged from a duplication of the preproinsulin gene followed by point mutations (Chan et al., 1993). Subsequently, IGF-I and IGF-II were thought to diverge from the common precursor gene (IGF) before the elasmobranchs diverged from the tetrapod lineage (Duguay et al., 1995). The finding of separate insulin and IGF-I receptors in hagfish suggests that these two receptors evolved from a common receptor very early in vertebrate evolution, prior to the divergence leading to separate IGF-I and IGF-II molecules. The IGF-II receptor, however, is a molecule structurally unrelated to the insulin or the IGF-I receptors and does not share a common ancestry with the receptors of the insulin/IGF-I family. The IGF-II receptor, also known as the cation-independent M6P receptor, probably originated from a duplication of the gene coding for an ancestral M6P receptor, which led to a cation-independent M6P receptor and a cation-dependent M6P receptor. It is thought that the cation-independent M6P receptor recently acquired the ability to bind IGF-II, assuming a new role.
Fish are the first group in the vertebrate tree from which there is evidence for the presence of distinct insulin and IGF-I molecules and distinct insulin and IGF-I receptors. During the course of evolution from fish to mammals, the primary sequences of insulin and IGF-I have been well conserved (Chan et al., 1993). Recent studies indicate that partial sequences of fish insulin and IGF-I receptors also show a high degree of similarity to the mammalian insulin and IGF-I receptors, respectively (Chan et al., 1997). Therefore, the structural characteristics of insulin and IGF-I and their receptors have been well conserved during vertebrate evolution. Despite the overall structural homology among the different vertebrate insulin receptors, as well as among the different IGF-I receptors, the small differences found among various species underlie important functional differences. This is evidenced quite clearly in skeletal muscle, a tissue that is a target for both insulin and IGF-I. A significant increase in the specificity and activation capacity, as indicated by tyrosine kinase activity, of the insulin receptor appears to have taken place in skeletal muscle during the evolution from fish to mammals (Párrizas et al., 1995a). These observations, coupled with the marked increase in the number of insulin receptors from fish to mammals, suggest that the insulin receptor has taken a predominant, more specialized, role in skeletal muscle during vertebrate evolution. In fact, insulin has a predominantly metabolic role in mammals, in which it is essential for maintaining metabolic homeostasis (Taylor, 1991). Nevertheless, insulin may also have a secondary role in cell growth and differentiation, processes that in mammals are predominantly regulated by IGF-I (LeRoith et al., 1991). By the same token, IGF-I may partially overlap with insulin's role in metabolism in mammals as evidenced by the known effects of IGF-I on glucose uptake and metabolism (Dohm et al., 1990; Boulware et al., 1992). In fish, the roles of insulin and IGF-I in the regulation of metabolism and growth, respectively, do not appear to be as differentiated as in mammals. In fish, insulin has a strong growth-promoting effect, although usually slightly weaker than IGF-I (Plisetskaya et al., 1994). To our knowledge there is little information on the possible effects of IGF-I in metabolism in fish, so that it cannot be determined at this point if IGF-I can overlap with insulin in the regulation of metabolism in fish.
Similar to the insulin receptor, the IGF-I receptor has also increased its specificity and activation capacity during the transition from fish to mammals, but not to the same extent as the insulin receptor (Párrizas et al., 1995a). Furthermore, the number of IGF-I receptors has increased from fish to mammals, despite the significant increase in the ratio of insulin/IGF-I receptor number. In vertebrates, the IGF-I receptor binds its own ligand (i.e., IGF-I) but also binds IGF-II, albeit with a lower affinity. It is thought that IGF-II exerts its actions through the IGF-I receptor, as well as through the insulin receptor, and not through the IGF-II receptor. Therefore, until the appearance of the IGF-II binding site in the M6P receptor, the three ligands of the insulin/IGF family (i.e., insulin, IGF-I and IGF-II) shared only two receptors (insulin receptor and IGF-I receptor). Our studies on the IGF-II binding in fish embryos suggest that a specific IGF-II receptor may have been present in early vertebrate evolution.
|
CONCLUSIONS |
|---|
|
TOP
SYNOPSISINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
Fish are the first vertebrate group which have a complete system of ligands and receptors for the insulin/IGF family. Fish have distinct insulin, IGF-I and IGF-II molecules and distinct and specific insulin, IGF-I and, possibly, IGF-II receptors. When studying the evolution of these receptors along the vertebrate phyla, one of the more interesting aspects is the predominance of IGF-I receptors over insulin receptors in muscle tissue of ectothermic vertebrates. Another interesting aspect is the marked increase in the number of insulin receptors, as well as its associated tyrosine kinase activity, during vertebrate evolution. Therefore, endothermic vertebrates have higher numbers of insulin receptors and higher activation capacity of these receptors in muscle tissue than ectothermic vertebrates, which is in agreement with the predominant role of insulin in the regulation of metabolism in mammals. On the other hand, the lower number of insulin receptors in fish muscle tissue, compared to those of IGF-I, may help explain the relative overlap of the functions of insulin and IGF-I that appears to take place in this vertebrate group.
|
ACKNOWLEDGMENTS |
|---|
We are indebted to Chiron Therapeutics for the gift of human recombinant IGF-I. We thank the Piscifactoria de Bagà, Departament de Medi Natural de la Generalitat de Catalunya, and especially Sr. Antonino Clemente, and L. Colom and V. Prat from the Barcelona Zoological Park, and J. Baró from Truites del Segre for providing the fish. This study was supported by grants from Dirección General de Enseñanza Superior e Investigación Científica (AGF98-0325 to J.G. and PB97-0902 to I.N.), CIRIT 1998SGR 00037 to J.G., NATO Collaborative grant to J.G. and FAIRCT 950174.
|
FOOTNOTES |
|---|
1 From the symposium A Tribute to Erika M. Plisetskaya: New Insights on the Function and Evolution of Gastroenteropancreatic Hormones presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 6–10 January 1999, at Denver, Colorado.
2 E-mail: planas{at}porthos.bio.ub.es
|
References |
|---|
|
TOP
SYNOPSISINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSReferences |
|---|
Adashi, E.Y., C.E. Resnick, and R.G. Rosenfeld. 1990. Insulin-like growth factor-I (IGF-I) and IGF-II hormonal action in cultured rat granulosa cells: Mediation via type I but not type II IGF receptors. Endocrinology, 126:216-222.
Amstrong, D.G., and C.O. Hogg. 1992. The expression of a putative insulin-like growth factor-I receptor gene in the liver of the developing chick. J. Mol. Endocrinol., 8:193-206.
Boulware, S.D., W.V. Tamborlane, L.S. Mathews, and R.S. Sherwin. 1992. Diverse effects of insulin-like growth factor 1 on glucose, lipid, and amino acid metabolism. Am. J. Physiol., 262:E130-E133.
Chan, S.J., Q.-P. Cao, S. Nagamatsu, and D.F. Steiner. 1993. Insulin and insulin-like growth factor genes in fishes and other primitive chordates. In P. Hochachka, T. Mommsen (eds.)Biochemistry and molecular biology of fishes, Vol. 2:.Elsevier, Amsterdam.
Chan, S.J., E.M. Plisetskaya, E. Urbinati, Y. Jin, and D.F. Steiner. 1997. Expression of multiple insulin and insulin-like growth factor receptor genes in salmon gill cartilage. Proc Natl Acad Sci U.S.A., 94:12446-12451.
Cowey, C.B., and M.J. Walton. 1989. Intermediary metabolism. In J.E. Halver (ed.)Fish Nutrition, pp. 259-329Academic Press, San Diego, California.
Dahms, N.M., M.A. Brzycki-Wessell, K.S. Ramanujam, and B. Seetharam. 1993. Characterization of mannose 6-phosphate receptors (MPRs) from opossum liver: Opossum cation-independent MPR binds insulin-like growth factor-II. Endocrinology, 133:440-446.
Dardevet, D., C. Sornet, D. Attaix, V.E. Baracos, and J. Grizard. 1994. Insulin-like growth factor 1 and insulin resistance in skeletal muscle of adult and old rats. Endocrinology, 134:1475-1484.
Dohm, G.H., C.W. Elton, M.S. Raju, N.D. Mooney, R. Dimarchi, W.J. Pories, E.G. Flickinger, S.M. Atkinson Jr., and J.F. Caro. 1990. IGF-1 stimulated glucose transport in human skeletal muscle and IGF-1 resistance in obesity and NIDDM. Diabetes, 39:1028-1032.[Abstract]
Drakenberg, K., V.R. Sara, S. Falkmer, S. Gammeltoft, C. Maake, and M. Reinecke. 1993. Identification of IGF-1 receptors in primitive vertebrates. Regul. Pept., 43:73-81.[CrossRef][Web of Science][Medline]
Duguay, S.J., S.J. Chan, T.P. Mommsen, and D.F. Steiner. 1995. Divergence of insulin-like growth factors I and II in the elasmobranch Squalus acanthias.. FEBS Lett., 371:69-72.[CrossRef][Web of Science][Medline]
Gutiérrez, J., and E.M. Plisetskaya. 1991. Insulin binding to liver plasma membranes of coho salmon during smoltification. Gen. Comp. Endocrinol., 82:466-475.[CrossRef][Web of Science][Medline]
Gutiérrez, J., M. Párrizas, N. Carneiro, M.A. Maestro, and J. Planas. 1993. Insulin and IGF-I receptors and tyrosine kinase activity in carp ovaries: changes with reproductive cycle. Fish Physiol Biochem., 11:247-254.[CrossRef]
Gutiérrez, J., M. Párrizas, M.A. Maestro, I. Navarro, and E.M. Plisetskaya. 1995. Insulin and IGF-I binding and tyrosine kinase activity in fish heart. J. Endocrinol., 146:35-44.
Hainaut, P., A. Kowalski, S. Giorgetti, E. Baron, and E. Van Obberghen. 1991. Insulin and insulin-like-growth-factor (IGF-I) receptors in Xenopus laevis oocytes. Biochem. J., 273:673-678.
Janicot, M., J.R. Flores-Riveros, and M.D. Lane. 1991. The insulin-like growth factor I (IGF-I) receptor is responsible for mediating the effects of insulin, IGF-I and IGF-II in Xenopus laevis oocytes. J. Biol. Chem., 266:9382-9391.
Kiess, W., G.D. Blickenstaff, M.M. Sklar, C.L. Thomas, S.P. Nissley, and G.G. Sahagian. 1988. Biochemical evidence that the type II insulin-like growth factor receptor is identical to the cation-independent mannose 6-phosphate receptor. J. Biol. Chem., 263:9339-9344.
Lappova, J., and B.N. Leibush. 1995. Receptor-mediated endocytosis of insulin in lower vertebrates: internalization and intracellular processing of 125I-insulin in isolated hepatocytes of lamprey and frog. Gen. Comp. Endocrinol., 100:1-9.[CrossRef][Web of Science][Medline]
Le Gac, F., M. Loir, P.-Y. Le Bail, and M. Ollitrault. 1996. Insulin-like growth factor (IGF-I) mRNA and IGF-I receptor in trout testis and in isolated spermatogenic and sertoli cells. Mol. Reprod. Dev., 44:23-35.[CrossRef][Web of Science][Medline]
Leibush, B., M. Párrizas, I. Navarro, Y. Lappova, M.A. Maestro, M. Encinas, E.M. Plisetskaya, and J. Gutiérrez. 1996. Insulin and insulin-like growth factor-I receptors in fish brain. Reg. Pep., 61:155-161.
LeRoith, D., M. Adamo, H. Werner, and C.T. Roberts Jr. 1991. Insulin-like growth factors and their receptors in normal physiology and pathologic states. Trends Endocrinol. Metab., 2:134-139.[CrossRef][Web of Science]
MacDonald, R.G., S.R. Pfeffer, L. Coussens, M.A. Tepper, C.M. Brocklebank, J.E. Mole, J.K. Anderson, E. Chen, M.P. Czech, and A. Ullrich. 1988. A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. Science, 239:1134-1137.
Maestro, M.A., E. Méndez, M. Párrizas, and J. Gutiérrez. 1997a. Characterization of insulin and insulin-like growth factor-I (IGF-I) ovarian receptors during the reproductive cycle of carp (Cyprinus carpio). Biol. Reprod., 56:1126-1132.[Abstract]
Maestro, M.A., J.V. Planas, S. Moriyama, J. Gutiérrez, J. Planas, and P. Swanson. 1997b. Ovarian receptors for insulin and insulin-like growth factor-I (IGF-I), and effects of IGF-I on steroid production by isolated follicular layers of the preovulatory coho salmon ovarian follicle. Gen. Comp. Endocrinol., 106:189-201.[CrossRef][Web of Science][Medline]
Morgan, D.O., J.C. Edman, D.N. Standring, V.A. Fried, M.C. Smith, R.A. Roth, and W.J. Rutter. 1987. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature, 329:301-307.[CrossRef][Medline]
Morrione, A., B. Valentinis, S.-Q. Xu, G. Yumet, A. Louvi, A. Efstratiadis, and R. Baserga. 1997. Insulin-like growth factor II stimulates cell proliferation through the insulin receptor. Proc. Natl. Acad. Sci. U.S.A., 94:3777-3782.
Nagamatsu, S., S.J. Chan, S. Falkmer, and D.F. Steiner. 1991. Evolution of the insulin gene super family. Sequence of a preproinsulin-like growth factor cDNA from the Atlantic hagfish.J. Biol. Chem., 266:2397-2402.
Palmer, T.N., and B.E. Ryman. 1972. Studies on oral glucose intolerance in fish. J. Fish. Biol., 4:311-319.[CrossRef]
Párrizas, M., N. Baños, J. Baró, J. Planas, and J. Gutiérrez. 1994a. Up-regulation of insulin binding in fish skeletal muscle by high insulin levels. Reg. Pept., 53:211-222.[CrossRef][Web of Science][Medline]
Párrizas, M., M.A. Maestro, N. Baños, I. Navarro, J. Planas, and J. Gutiérrez. 1995a. Insulin/IGF-I binding ratio in skeletal and cardiac muscles of vertebrates: A phylogenetic approach. Am. J. Physiol., 269:R1370-R1377.
Párrizas, M., J. Planas, E.M. Plisetskaya, and J. Gutiérrez. 1994b. Insulin receptor and its tyrosine kinase activity in skeletal muscle of carnivorous and omnivorous fish. Am. J. Physiol., 266:R1944-1950.
Párrizas, M., E.M. Plisetskaya, J. Planas, and J. Gutiérrez. 1995b. Abundant insulin-like growth factor-1 (IGF-I) receptor binding in fish skeletal muscle. Gen. Comp. Endocrinol., 98:16-25.[CrossRef][Web of Science][Medline]
Pashmforoush, M., S.J. Chan, and D.F. Steiner. 1996. Structure and expression of the insulin-like peptide receptor from amphioxus. Mol. Endocrinol., 10:857-866.
Planas, J.V., E. Méndez, N. Baños, E. Capilla, I. Navarro, and J. Gutiérrez. 2000. Insulin and IGF-I receptors in trout adipose tissue are physiologically regulated by circulating hormone levels. J. Exp. Biol., 203:1153-1159.[Abstract]
Plisetskaya, E.M., S.J. Duguay, and C. Duan. 1994. Insulin and insulin-like growth factor-I in salmonids: comparison of structure, function and expression. In K.G. Davey, R.E. Peter, S.S. Tobe (eds.)Perspective in comparative endocrinology, pp. 226-233Nat. Res. Couns. Ontario, Canada.
Reinecke, M., and C. Collet. 1998. The phylogeny of the insulin-like growth factors. Int. Rev. Cytol., 183:1-94.[Web of Science][Medline]
Stewart, E.H., and P. Rotwein. 1996. Growth, differentiation, and survival: Multiple physiological functions for insulin-like growth factors. Physiol. Rev., 76:1005-1026.
Taylor, R. 1991. Insulin action. Clin. Endocrinol., 34:159-171.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||