Membrane depolarization and calcium influx induce glucagon gene transcription in pancreatic islet cells through the cyclic AMP-responsive element

Glucagon-producing pancreatic islet cells generate calcium-dependent action potentials. By the control of calcium influx through voltage-gated calcium channels, calcium is a tightly regulated second messenger in these cells. It is unknown whether calcium is a signal for glucagon gene transcription....

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Bibliographic Details
Published in:The Journal of biological chemistry 1993-03, Vol.268 (7), p.5168-5177
Main Authors: SCHWANINGER, M, GUNDULA LUX, BLUME, G, OETIJEN, E, HIDAKA, H, KNEPEL, W
Format: Article
Language:English
Subjects:
Biological and medical sciences
Calcium - metabolism
Calcium Channels - metabolism
Calcium-Calmodulin-Dependent Protein Kinases
Cyclic AMP - metabolism
Cyclic AMP Response Element-Binding Protein - metabolism
Fundamental and applied biological sciences. Psychology
Glucagon - genetics
Ion Channel Gating
Islets of Langerhans - metabolism
Islets of Langerhans - physiology
Membrane Potentials
Molecular and cellular biology
Molecular genetics
Phenotype
Protein Kinases - metabolism
Regulatory Sequences, Nucleic Acid
Transcription, Genetic
Transcription. Transcription factor. Splicing. Rna processing
Tumor Cells, Cultured
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Summary:Glucagon-producing pancreatic islet cells generate calcium-dependent action potentials. By the control of calcium influx through voltage-gated calcium channels, calcium is a tightly regulated second messenger in these cells. It is unknown whether calcium is a signal for glucagon gene transcription. Therefore, rat glucagon reporter fusion genes were transiently transfected into pancreatic islet cell lines. High potassium-induced membrane depolarization activated glucagon gene transcription. The effects of a calcium chelator, calcium channel blockers, calmodulin antagonists, and an inhibitor of calcium/calmodulin-dependent protein kinase II (CaM kinase II) indicate that depolarization-induced glucagon gene transcription depends on calcium influx and CaM kinase II. The depolarization-responsive element was mapped to the glucagon cAMP-responsive element (CRE). The CRE-binding protein CREB was shown, by using GAL4-CREB fusion proteins, to function as a depolarization-regulated transcription factor in pancreatic islet cells. Membrane depolarization and cAMP had synergistic effects on glucagon gene transcription. These results suggest that rat glucagon gene transcription is regulated by membrane electrical activity and calcium influx in pancreatic islet cells. This signal may be transmitted via CaM kinase II and CREB to the glucagon CRE.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)53516-X