Date of Award

1-1-2009

Document Type

Masters Thesis

Degree Name

M.S.

Organizational Unit

Biological Sciences

First Advisor

Joseph K. Angleson

Second Advisor

Robert Dores

Third Advisor

Nancy Lorenzon

Keywords

Alpha-MSH regulated cell signaling, Melanocyte-stimulating hormone, Diabetes, Hyperglycemia

Abstract

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.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Liang Liang

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

67 p.

Discipline

Molecular biology

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