title: Self-inducible secretion of glucagon-like peptide-1 (GLP-1) that allows MIN6 cells to maintain insulin secretion and insure cell survival.
abstract: 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.
authors: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
authors: Koji
authors: K
authors: Nakashima
authors: Masashi
authors: M
authors: Shimoda
authors: Sumiko
authors: S
authors: Hamamoto
authors: Fuminori
authors: F
authors: Tatsumi
authors: Hidenori
authors: H
authors: Hirukawa
authors: Kazuhito
authors: K
authors: Tawaramoto
authors: Yukiko
authors: Y
authors: Kanda
authors: Kohei
authors: K
authors: Kaku
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D050882:CREB-Binding Protein / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000077270:Exenatide; D005136:Eye Proteins / Q000096:biosynthesis; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D018613:Microscopy, Confocal; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D052336:Proglucagon / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis; D014688:Venoms / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D005136:Eye Proteins; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018398:Homeodomain Proteins; D007328:Insulin; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D012097:Repressor Proteins; D015534:Trans-Activators; D014688:Venoms; C084010:pancreatic and duodenal homeobox 1 protein; C083773:exendin (9-39); D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D005947:Glucose