Doctoral thesis, 2015
Insulin-like growth factor-I in the domestic catStrage, Emma
AbstractInsulin-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.
KeywordsAcid-labile subunit; Acromegaly; Diabetes mellitus; Growth hormone; Insulin; Insulin-like growth factor binding proteins; Ternary complex
Published inActa 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