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Title: /sup 125/I and /sup 125/I-glucagon metabolism in rat liver

Thesis/Dissertation ·
OSTI ID:6067513

This report suggests that the time course and enzymatic nature of /sup 125/I-insulin degradation in vivo correlates with major subcellular locations of autoradiographic grains during the course of endocytosis. /sup 125/I-insulin and hormone fragments were detected in liver extracts using reverse-phase high performance liquid chromatography (RP-HPLC). /sup 125/I-insulin was rapidly degraded in vivo. Comparison with autoradiographic studies suggests insulin degradation begins before substantial lysosomal localization is observed. Studies using an isolated perfused rat liver system suggest that the plasmalemma does not mediate rapid insulin degradation as observed in vivo. The author, therefore, sought to identify /sup 125/I-insulin fragments which typified the activities of the most-implicated intracellular degradative systems: acidic lysosomal proteolysis, a microsomal reductive system such as glutathione-insulin transhydrogenase (GIT), and a cytosolic neutral proteolytic system such as insulin protease. Significant GIT activity was not observed in vivo nor in vitro with liver homogenates. Purified liver insulin protease degraded /sup 125/I-insulin in a fashion similar to that observed in vivo. Lysosomal activity was observed only after a lag of approximately 10 minutes. Complete degradation of /sup 125/I-glucagon in vivo occurred within 1 minute of hormone injection.

Research Organization:
Minnesota Univ., Minneapolis (USA)
OSTI ID:
6067513
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English