Date of Award
Joseph K. Angleson
Alpha-MSH regulated cell signaling, Melanocyte-stimulating hormone, Diabetes, Hyperglycemia
Peripheral injection of α-MSH promotes glucagon secretion in POMC knockout mice, suggesting the role of α-MSH in regulation of pancreatic α cells. However, the underlying mechanisms remain unknown. This study investigated the stimulatory effect of α-MSH on mice pancreatic α cell line αTC1-6 cells in cell signaling pathway as well as glucagon secretion. In normal level of glucose, application of α-MSH stimulated Ltype Ca2+ current induced Ca2+ induced Ca2+ release (CICR) and membrane hyperpolarization. Increase of [cAMP]c was also observed when α-MSH was applied with IBMX. Acute hypoglycemia-induced CICR via N- and L-type Ca2+ channels was overridden by typical α-MSH response. Hypoglycemia with IBMX also triggered Ca2+- stimulated cAMP production. In the presence of α-MSH, insulin failed to inhibit acute hypoglycemia-induced CICR. Finally, stimulation of α-MSH increased glucagon secretion significantly. These findings indicate that α-MSH promotes glucagon secretion in αTC1-6 cells by elevating micro-regional [cAMP]c and [Ca2+]c.
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Liang, Liang, "Alpha-MSH Regulated Cell Signaling in Pancreatic Alpha Cells" (2009). Electronic Theses and Dissertations. 859.
Received from ProQuest