Self-inducible secretion of glucagon-like peptide-1 (GLP-1) that allows MIN6 cells to maintain insulin secretion and insure cell survival

Autor: Kazuhito Tawaramoto, Koji Nakashima, Hidenori Hirukawa, Kohei Kaku, Masashi Shimoda, Fuminori Tatsumi, Yukiko Kanda, Sumiko Hamamoto
Rok vydání: 2011
Předmět:
endocrine system
medicine.medical_specialty
PAX6 Transcription Factor
Cell Survival
Cellular differentiation
Cell
Apoptosis
Biology
Proglucagon
Biochemistry
Glucagon-Like Peptide-1 Receptor
Cell Line
Endocrinology
Glucagon-Like Peptide 1
Internal medicine
Insulin Secretion
medicine
Receptors
Glucagon
Humans
Insulin
Paired Box Transcription Factors
Secretion
RNA
Messenger
Autocrine signalling
Eye Proteins
Molecular Biology
Homeodomain Proteins
Microscopy
Confocal
Venoms
digestive
oral
and skin physiology
Cell Differentiation
Glucagon-like peptide-1
Antibodies
Neutralizing
CREB-Binding Protein
Peptide Fragments
Cell biology
Repressor Proteins
Autocrine Communication
medicine.anatomical_structure
Glucose
Cell culture
Trans-Activators
Exenatide
Signal transduction
Peptides
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Zdroj: Molecular and cellular endocrinology. 349(2)
ISSN: 1872-8057
Popis: Based on the hypothesis that MIN6 cells could produce glucagon-like peptide-1 (GLP-1) to maintain cell survival, we analyzed the effects of GLP-1 receptor agonist, exendin-4 (Ex4), and antagonist, exendin-(9-39) (Ex9) on cell function and cell differentiation. MIN6 cells expressed proglucagon mRNAs and produced GLP-1, which was accelerated by Ex4 and suppressed by Ex9. Moreover, Ex4 further enhanced glucose-stimulated GLP-1 secretion, suggesting autocrine loop-contributed amplification of the GLP-1 signal. Ex4 up-regulated cell differentiation- and cell function-related CREBBP, Pdx-1, Pax6, proglucagon, and PC1/3 gene expressions. The confocal laser scanning images revealed that GLP-1 positive cells were dominant in the early stage of cells, but positive for insulin were more prominent in the mature stage of cells. Ex4 accelerated cell viability, while Ex9 and anti-GLP-1 receptor antibody enhanced cell apoptosis. MIN6 cells possess a mechanism of GLP-1 signal amplification in an autocrine fashion, by which the cells maintained insulin production and cell survival.
Databáze: OpenAIRE
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