Date of Award
Doctor of Philosophy
Walter H. Hsu
The first study purpose was to investigate the glucose dependency of arginine vasopressin (AVP)-induced insulin, glucagon and somatostatin release from the perfused rat pancreas. AVP (30 or 300 pmol/L) was tested in the presence of glucose concentrations of 0, 1.4, 5.5 (basal level), or 20 mmol/L. The findings from this study suggested that AVP may increase insulin and glucagon release by a direct action on beta- and alpha-cells, respectively. These increases are glucose-dependent; the higher the glucose concentration, the greater the enhancement of AVP-induced insulin release. In contrast, the lower the glucose concentration, the greater the enhancement of AVP-induced glucagon release. AVP not only can enhance glucose-induced insulin release, but also can initiate insulin release. alpha-cells are much more sensitive to AVP than beta-cells in hormone release. Furthermore, our results confirmed the previous findings that hypoglycemia directly increases glucagon and decreases insulin release.;The second study purpose was to characterize the mechanisms by which cAMP/PKA enhances AVP-induced glucagon release and provide further details in the intracellular molecular components involved in this enhancement, particularly at the level of exocytosis. Increasing intracellular cAMP levels by forskolin or IBMX enhanced AVP-induced glucagon release from the perfused rat pancreas and the clonal alpha-cells InR1G9. cAMP/PKA did not increase [Ca 2+]i nor did it;enhance AVP-induced [Ca2+]i increase. Forskolin and IBMX enhanced AVP-induced glucagon release in Ca2+-containing but not in Ca2+-free medium. InR1G9 cells were loaded with styryl dye FM1-43 to measure the size of readily releasable pool (RRP). The combination of AVP and forskolin induced higher increase in fluorescence intensity than AVP or forskolin alone, which reflects an increase in the size of the RRP. Secretory granules in the reserve pool (RP) are thought to be reversibly connected to the actin-based cytoskeleton by synapsin I. Pretreatment with antisynapsin I antibody abolished the effect of forskolin/AVP-induced glucagon release. In addition, FM1-43 loading experiments showed that synapsin I is involved in recruitment of secretory granules from RP to RRP. Our results suggested that cAMP, acting through PKA, increases the number of secretory granules in the RRP by mobilization of granules from the RP, an action mediated by synapsin I.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu
Ehab A.H. Abu-Basha
Abu-Basha, Ehab A. H., "Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase " (2002). Retrospective Theses and Dissertations. 353.