Development in the annual killifish Austrofundulus limnaeus can follow two distinct developmental trajectories. Typical development includes the entrance of embryos into a state of metabolic and developmental arrest termed diapause. Alternately, embryos can escape diapause and develop directly without pause. These two trajectories are characterized by differences in the rate and timing of developmental, morphological, and physiological traits. Insulin and Insulin-like growth factor (IGF) signaling (IIS) is known to regulate entrance into diapause in a variety of invertebrates. In this thesis I explore the possible role of IGFs in the regulation of development and diapause in embryos of A. limnaeus. Here I report stage-specific expression of IGF-I and II proteins and their associated mRNA transcripts. Patterns of IGF-I protein expression are consistent with IGF signaling playing a major role in supporting the escape trajectory. In addition, treatment of embryos with a potent inhibitor of the IGF-I receptor (IGF1R) mimics the diapause developmental pattern even under conditions that should favor direct development. Evaluation of mRNA gene expression patterns in the two developmental trajectories suggests a role for IGF-I signaling through the RAS-MAPK-ERK pathway, which may be promoting the escape phenotype. Additionally, IGF-I activity may be enhanced in escape trajectory embryos though upregulation of IGF binding protein 2 (IGFBP-2) mRNA. These data suggest a major role for IGF signaling in the promotion of the escape trajectory, and thus we predict that specific mechanisms are in place in diapause-bound embryos that block IGF signaling and thus promote entrance into diapause. The data presented here suggest that blocking IGF signaling is critical for induction of diapause, but also suggests that other signaling pathways are likely also at play. Other pathways such at the TGF-beta signaling molecules and SMAD pathway, may also be involved in the direct regulation of the diapause phenotype, as has been shown for other animal models of developmental arrest.

Thesis (Ph. D.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains ix, 109 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 88-104).

Insulin-like growth factor-I (IGF-I) is a known stimulator of glucose transport. IGF binding protein 1 (IGFBP1) is a protein that regulates the actions of IGF-I by binding to IGF-I which alters it's ability to bind to the IGF-I receptor. Diet and exercise may influence this system. While IGFBP1 levels increase with fasting or prolonged exercise, feeding will reverse this elevation. The intent of this study was to determine if an in vivo manipulation of IGFBP1 affects in vitro glucose transport in the rat soleus. Sixteen male Spaque Dawley rats were fasted for 12 hours. Half of the animals were then allowed a two hour ad libitum refeeding period. Animals were anesthetized and had their soleus muscles removed. Muscles were then randomly assigned to one of four treatment groups. Treatments involved an incubation in either 4 or 8 mM glucose in either the presence or absence of IGF-I (75 ng x ml"'). Final incubation for all treatment groups included [3H]-3-O-methylglucose (437 µCi x mM-) for the measurement of glucose transport. Following incubation, muscles were weighed, homogenized in 1 ml of 10% trichloroacetic acid, and centrifuged to precipitate out protein. 100 µl of the supernatant was added to 3 ml of scintillation fluid and analyzed in a scintillation counter. Glucose transport was determined by 3H activity. A statistical analysis of the various groups shows that there is no significant difference between fasted and refed animal for any specific treatment. However, when all the fasted and refed animals area grouped, glucose transport rate is significantly greater (p<0.05) in fasted (3.59 ± 0.44 µM x ml"' x hr) animals than in refed animals (2.56 ± 0.27 µM x ml"' x hr'). Additionally, muscles that were treated with IGF-I in 8 mM glucose demonstrated a greater rate of glucose transport (5.12 ± 0.68 µM x ml-1 x hr') than all other treatments (2.13 ± 0.39 to 2.90 ± .33 µM x ml-' x hr'). This study showed that IGF-I is a stimulator of glucose transport in an 8 mM glucose media. Additionally, the results show that glucose transport is greater if the animals are fasted. The differences between fasted and refed animals demonstrated in this study supports the hypothesis that diet manipulated IGFBP1 levels are able to alter the biological effects of IGF-I. / School of Physical Education

Bibliography: leaves 112-140. / xi, 141, [39] leaves, [8] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aims of this thesis are to determine the initial cleavage sites of purified pepsin in long-R3-IGF-I and assess whether the resulting cleavages affect biological activity, to design and produce analogues of long-R3-IGF-I which contain amino acid substitutions, to characterise the resulting analogues for pepsin resistance and retention of biological activity and to assess the stability of the long-R3-IGF-I analogues under in vivo conditions using luminal stomach flushings. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1996

Thesis (Ph. D.)--University of Adelaide, Dept.of Biochemistry, 1992. / Includes bibliographical references (leaves 79-101).

Thesis (Ph. D.)--University of Missouri--Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 111-127). Also available on the Internet.

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references.

Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references (leaves 164-181). Also available on the Internet.

Thesis (Ph.D.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references (leaves 164-181). Also available on the Internet.

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