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UBC Theses and Dissertations

Insulin-like growth factor-I and the endocrine pancreas McClean, Carole Anne


Insulin-like growth factor-I (IGF-I) has been determined to have both mitogenic and insulin-like metabolic effects on many tissue types. IGF-I has previously been shown to be secreted from, and to stimulate fi-cell activity in fetal pancreas. The present studies were performed in order to determine if IGF-I was present in adult endocrine pancreatic tissue, and if local IGF-I influenced insulin secretion in the adult islet. IGF-I immunoreactivity was present only in endocrine tissue and double staining techniques revealed that IGF-I immunoreactivity was colocalized only with insulin immunoreactivity. These results were confirmed at the electron microscope level, where IGF-I immunoreactivity was localized to B-cells, and furthermore, only to mature B-cell granules. In order to study pancreatic IGF-I concentrations and secretion, an IGF-I RIA was established, and a method of separating IGF-I from its binding proteins was validated. GH, the primary stimulator of IGF-I secretion from the liver and many other tissues, did not influence IGF-I secretion from either perfused pancreas, or isolated islet preparations. Nor did the insulin secretagogues GIP and glucose. Islet extracts subjected to high performance liquid chromatography (HPLC) revealed an elution peak, corresponding to that of the IGF-I standard, which indicated a low level of IGF-I in adult rat islets (approximately 1 pg/islet). IGF-I receptors were found to be present in islet tissue, as indicated by autoradiographic as well as by 1 2 5I-IGF-I binding studies. IGF-I stimulated insulin secretion from isolated adult rat islets, particularly at the highest level tested (170.0 nM). This effect was dependent on a stimulatory levels of glucose (8.9, 17.8 mM). Furthermore, low concentrations of IGF-I (1.7 nM, 17.0 nM) potentiated maximal GIP stimulated (10 nM) insulin secretion. Given findings by others that IGF-I can inhibit insulin secretion from the adult islet, it is proposed that in vitro study conditions influence the physiology of pancreatic IGF-I. The stimulatory effect of IGF-I on insulin secretion found in the present study suggests a fetal-like response of fl-cells to IGF-I and it is proposed that the inclusion of fetal serum in islet culture medium may result in adult islets showing fetal characteristics.

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