Comparatative studies on the IGF system in vertebrates : studies in rats, and in bony, cartilaginous, and jawless fish

Abstract

Numerous studies have shown the importance of insulin-like growth factors (IGFs) for cellular growth, differentiation and metabolism in mammalian vertebrates. The mammalian IGF system, consists of IGF-1 and IGF-2, the IGF binding proteins (IGFBPs), and the type1 and type 2 IGF receptors. In non-mammalian vertebrates, knowledge of the prevalence and possible physiological role of the IGF system is greatly lacking, although its existence has been supported by results of recent studies.

The presence of IGF-like peptides was investigated in five species from three classes of non-mammalian vertebrates; osteichthyes, chondrichthyes and cyclostomi. Using acidsize-exlusion chromatography and IGF specific radioreceptor and radioimmuno assays,IGF-1 and IGF-2 like peptides could be detected in serum and tissues of chondrichthyes and osteichthyes with some species variations. These peptides most likely represent the fish variants of mammalian IGF-1 and IGF-2. Two additional peaks were often observed with the assays, a high molecular weight peak, possibly indicating the presence of IGFBPs, and a low molecular weight peak (2-4 kDa) which may be a degradation product of larger IGF peptides. Immunohistochemical techniques were used to localize IGF-like immunoreactive cells. IGF-1-like immunoreactivity was observed in endocrine cells of the open type in the gut mucosa and in endocrine cells of the pancreas/islet organ of daddy sculpin, sting ray and hagfish. The majority of the IGF-1-like immunoreactivity, in sting ray pancreas, was observed to co-exist with somatostatin-immunoreactivity. In sting ray as well as in rat pancreas, co-localization of IGF-2-like- and insulin-immunoreactivity was observed in the endocrine cells of the islets. The results indicate a particularly conservative evolution of the IGF-2 peptide in pancreas.

Competitive binding curves and affinity labeling studies on brain and liver membranes in daddy sculpin, sting ray and hagfish only identified a type 1-like IGF receptor based on two criteria: IGF-1 and IGF-2 were almost equally potent and insulin much less potent in displacing membrane bound 125I-IGF-1 and 125I-IGF-2, and the labeled protein had a molecular weight of approximately 100-120 kDa under reducing conditions. Similarly, results from displacement studies, on barramundi liver membrane, indicated a type 1-like IGF receptor. Acute insulin-like effects of intraperitoneally injected rhlGF-1 were investigated in barramundi. A bolus of rhlGF-1 (17 pmol/g body weight) significantly decreased blood glucose levels and stimulated the incorporation of 1 C-glucose in muscle glycogen. Comparable effects of IGF-1 were observed in rats.

In conclusion, the presence of IGFs and one of their receptors, in species belonging to classes which diverged early during vertebrate evolution, supports the hypothesis that the IGFs diverged from insulin before or at the time for the appearance of the vertebrates. The conservation of IGF-like peptides and the type 1-like receptor during evolution suggests a fundamental biological importance. This is supported by studiesdemonstrating comparable acute metabolic effects of IGF-1 in a mammalian and anosteichthyean species.