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Doctoral thesis, 2015

Insulin-like growth factor-I in the domestic cat

Strage, Emma

Abstract

Insulin-like growth factor-I (IGF-I) has growth promoting effects as well as insulin-like actions on metabolism. IGF-I associates with a family of six high affinity IGF-binding proteins (IGFBPs) and these interfere in immunoassays for IGF-I. The role of binding of IGF-I to IGFBP-3, together with a third protein (the acid-labile subunit), to form a high molecular mass ternary complex, is not known in cats. In adult humans the ternary complex is the dominant circulating form. The cat is a strict carnivore with different metabolism to other species, which may include differences in the IGF system. In clinical practice serum IGF-I is used routinely for screening for acromegaly in cats with diabetes mellitus (DM). The overall aim of this thesis was to determine factors regulating IGF-I concentrations in health and disease. Enzyme-linked immunosorbent assays for measuring feline IGF-I and insulin were validated. It is recommended that laboratories, in validating their assays, should be aware of position effects on assay plates and, for IGF-I assays, interference by circulating IGFBPs. For IGF-I, between animal variation was high (~65%) while within animal variation was considerable lower (~8%). These values for biological variation can now be used in interpreting clinical results after repeated sampling in screening for, and in the management of, acromegaly. IGF-I concentrations were related to the amount of the ternary complex in healthy and diabetic cats. The ternary complex was the dominating circulating form only in cats with high IGF-I concentrations. There was a wide range of IGF-I concentrations in both healthy and diabetic cats that was in part related to variation in weight. When using IGF-I as a screening tool for acromegaly in diabetic cats, glycaemic control should also be taken into consideration. IGF-I concentrations increased in response to insulin treatment and concentrations at 2-4 weeks were higher in cats that later went into remission. In conclusion, in contrast to adult humans, circulating IGF-binding forms vary across the wide range of IGF-I concentrations in the cat. It is recommended that reference intervals for healthy cats are developed, stratifying by weight. IGF-I shows promise as a predictive marker for remission in feline diabetes mellitus.

Keywords

Acid-labile subunit; Acromegaly; Diabetes mellitus; Growth hormone; Insulin; Insulin-like growth factor binding proteins; Ternary complex

Published in

Acta Universitatis Agriculturae Sueciae
2015, number: 2015:124
ISBN: 978-91-576-8446-2, eISBN: 978-91-576-8447-9
Publisher: Department of Clinical Sciences, Swedish University of Agricultural Sciences

Authors' information

Swedish University of Agricultural Sciences, Department of Clinical Sciences

UKÄ Subject classification

Clinical Science

URI (permanent link to this page)

https://res.slu.se/id/publ/68749