Bibliography: p. 190-234. / 276 p. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to directly test the hypothesis that restricting placental delivery of oxygen and nutrients to the fetus restricts fetal growth, in part by reducing endogenous production of insulin like growth factor-I / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1999?

1 v. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1994

xxiii, 222 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Insulin-like growth factor-I circulates at high concentrations in blood, mainly complexed with IGF-binding proteins. The main objective of the thesis is to determine the general role played by plasma IGF-binding proteins in the regulation of IGF transfer from blood to tissues. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1994

Insulin-like growth factor-1 (IGF-1) is essential for oligodendrocyte (OL) development, promoting their survival, proliferation and differentiation. Furthermore, IGF-1 null mutant mice have a decrease in CNS myelination and in the number of OL progenitors (OLPs). IGF-1 interacts with the Type I IGF receptor to activate two main downstream signalling pathways, the PI3K/Akt and the Ras-Raf-MEK/ERK cascades, which mediate survival or proliferation of OLPs. The objective of this study is to elucidate the transduction pathways involved in IGF-I-stimulated protein synthesis, important for growth and differentiation of OLs. In other cellular systems, the PI3K/Akt pathway is involved in protein translation. mTOR and the p70 S6 kinase are downstream effectors that phosphorylate translation initiation factors (e.g. eIF-4E) and their regulators (e.g. 4E-BP1). OLPs were obtained from primary cultures and were treated with IGF-1 with or without inhibitors LY294002 or wortmannin (PI3K), rapamycin (mTOR), Akt III or IV, an adenovirus with a dominant negative form of Akt or PD98059 (ERK). Protein synthesis was assessed by metabolic labeling with [35S]-methionine, and protein phosphorylation by Western blotting. Results from the former showed that IGF-1 stimulates protein synthesis in a dose-dependent manner. Moreover, IGF-1 increases protein synthesis in OLPs through PI3K, mTOR, Akt and ERK activation. Concordantly, Western blot analysis reveals that IGF-1 stimulates phosphorylation of Akt, mTOR, ERK, S6 and 4E-BP 1. Activation of S6 and inactivation of 4E-BP1 occur through phosphorylation and are required for protein synthesis to take place. These events are dependent on the upstream activation of PI3K, Akt and mTOR.

The study of diabetes mellitus is vital in this day and age because its incidence is increasing at an alarming rate. Diabetes results in the loss of function of beta-cells within the pancreas. Insulin resistance contributes to diabetes but the human body can compensate in various ways such as increasing the islet cell mass, glucose disposal and insulin secretion, in order to prevent the onset of diabetes. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are two integral hormones important in both glucose homeostasis and islet cell growth. Early studies using cultured islet cells have demonstrated positive regulation of beta-cell growth by both GH and IGF-I. To evaluate their relevance on normal beta-cell growth, compensatory growth, as well as in insulin responsiveness, we have used two mouse models that represent opposite manipulations of the GH/IGF-I axis. Specifically, the growth hormone receptor gene deficient (GHR-/-) and the IGF-I overexpression (MT-IGF) mice, to help understand the role of glucose homeostasis and islet cell growth in the GH/IGF-I axis. GH is essential for somatic growth and development as well as maintaining metabolic homeostasis. It is known that GH stimulates normal islet cell growth. Moreover, GH may also participate in islet cell overgrowth and compensate for insulin resistance induced by obesity. To determine whether the islet cell overgrowth is dependent on GH signaling, we studied the response of GHR-/- mice to high-fat diet (HFD)-induced obesity. We also studied the insulin responsiveness in GHR-/- mice. On the other hand, IGF-I promotes embryonic development, postnatal growth and the maturation of various organ systems. The notion that IGF-I stimulates islet cell growth has been challenged in recent years by results from IGF-I and receptor gene targeted models. We have characterized MT-IGF mice which overexpress the IGF-I gene. / The results of our studies indicate that (1) GH is essential for normal islet cell growth, but not required for compensatory overgrowth of the islets in response to obesity, (2) GHR gene deficiency caused delayed insulin responsiveness in skeletal muscle; in contrast to elevated insulin sensitivity in the liver; (3) although overexpression does not stimulate islet cell growth, a chronic IGF-I elevation caused significant hypoglycemia, hypoinsulinemia, and improved glucose tolerance, (4) finally IGF-I overexpression mice are resistant to experimental diabetes.

Bibliography :leaves 250-302. / xix, 302, [19] leaves, [4] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Results suggest that IGF-I peptides significantly influence gastrointestinal growth in normal adult and suckling rats and indicate they may have therapeutic implications both in conditions of impaired gut function in the adult gastrointestinal tract and in the treatment of gut disease in the immature intestine. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics & Gynaecology, 1995?

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Includes bibliographical references (leaves 159-213) Shows that IGF-I peptides are effective in diminishing post-surgical catabolism and enhancing adaptive gut hyperplasia in rats recovering from massive small bowel resection.

Includes bibliographical references (leaves 188-217) Insulin-like growth factor-I circulates at high concentrations in blood, mainly complexed with IGF-binding proteins. The main objective of the thesis is to determine the general role played by plasma IGF-binding proteins in the regulation of IGF transfer from blood to tissues.