Insulin dependent diabetes mellitus (IDDM) causes alterations in skeletal muscle at the biochemical and functional levels. Early signals initiating processes of muscle transformation are not known. One hypothesis suggests that alterations in energy state of a muscle may be causally related to altered gene expression. / The mechanistic basis of diabetes induced changes in energy supply and demand in skeletal muscle was evaluated. Experiments utilized an animal model of the disease, in which a condition similar to IDDM was induced in mice by injection of streptozotocin (STZ). The contents of phosphorous metabolites in quiescent fast and slow skeletal muscle were examined using phosphorous nuclear magnetic resonance spectroscopy and HPLC. STZ-injection decreased ATP, PCr, and the free energy of hydrolysis of ATP in slow twitch soleus (SOL) muscle, but not in the fast-twitch extensor digitorum longus (EDL). Maximal activities of selected enzymes, determined spectrophotometrically, also were decreased in SOL, but not in EDL. Alterations in contractile protein isoform composition occurred in both EDL and SOL, and the pattern of change was consistent with a fast to slow fiber-type transformation. In SOL, decreases in metabolite content preceded alterations in myosin expression at both protein and transcript levels. Alterations in the myosin isoform composition of the EDL occurred on a time scale consistent with those in SOL. / Myogenic factor transcript analysis demonstrates that expression of MRF4 is moderately increased after 5 weeks of STZ-diabetes in both EDL and SOL. These results suggest against involvement of fiber regeneration or processes of denervation mediating early changes in contractile proteins. / Decreases in phosphorous metabolite content are among the earliest changes in SOL from STZ-diabetic mice. Further, the temporal sequence of change is consistent with the hypothesis that intracellular energy state of muscle is mechanistically linked to alterations in gene expression. In fast twitch EDL it is suggested that exaggerated alterations in phosphorus metabolites occur during contraction. Thus, STZ-diabetes induced changes in energy state and contractile protein expression also may be causally related in the EDL. / Source: Dissertation Abstracts International, Volume: 56-03, Section: B, page: 1195. / Major Professor: Timothy S. Moerland. / Thesis (Ph.D.)--The Florida State University, 1995.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_77389 |
| Contributors | Fewell, Jason Glenn., Florida State University |
| Source Sets | Florida State University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | 133 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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