Date of Award
Joseph K. Angleson
Peripheral injection of &alpha-MSH promotes glucagon secretion in POMC knockout mice, suggesting the role of &alpha-MSH in regulation of pancreatic &alpha cells. However, the underlying mechanisms remain unknown. This study investigated the stimulatory effect of &alpha-MSH on mice pancreatic &alpha cell line &alphaTC1-6 cells in cell signaling pathway as well as glucagon secretion. In normal level of glucose, application of &alpha-MSH stimulated L-type Ca2+ current induced Ca2+ induced Ca2+ release (CICR) and membrane hyperpolarization. Increase of [cAMP]c was also observed when &alpha-MSH was applied with IBMX. Acute hypoglycemia-induced CICR via N- and L-type Ca2+ channels was overridden by typical &alpha-MSH response. Hypoglycemia with IBMX also triggered Ca2+-stimulated cAMP production. In the presence of &alpha-MSH, insulin failed to inhibit acute hypoglycemia-induced CICR. Finally, stimulation of &alpha-MSH increased glucagon secretion significantly. These findings indicate that &alpha-MSH promotes glucagon secretion in &alphaTC1-6 cells by elevating micro-regional [cAMP]c and [Ca2+]c.
Liang, Liang, "Alpha-MSH regulated cell signaling in pancreatic alpha cells" (2009). Electronic Theses and Dissertations. 859.
Recieved from ProQuest