GABA coordinates with insulin in regulating secretory function in pancreatic INS-1 β-cells

Pancreatic islet β-cells produce large amounts of γ-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing α-cells via type-A GABA receptors (GABA(A)Rs). We and others recently reported that islet β-cells also express GABA(A)Rs and that activ...

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Bibliographic Details
Published in:PloS one 2011-10, Vol.6 (10), p.e26225-e26225
Main Authors: Bansal, Paul, Wang, Shuanglian, Liu, Shenghao, Xiang, Yun-Yan, Lu, Wei-Yang, Wang, Qinghua
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Activation
Animals
Apoptosis
Autocrine signalling
Biology
C-Peptide - metabolism
Cell Line, Tumor
Data processing
Departments
Depolarization
Diabetes
Endocrinology
Enzyme inhibitors
Extracellular signal-regulated kinase
gamma-Aminobutyric Acid - pharmacology
Gene expression
Glucagon
Glucose
Inhibition
Insulin
Insulin - pharmacology
Insulin secretion
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - metabolism
Kinases
Medicine
Metabolism
Obesity
Pancreas
Pharmacology
Physiology
Picrotoxin
Radioimmunoassay
Rats
Receptors
Receptors, GABA-A - metabolism
Rodents
Secretion
Signal Transduction - drug effects
Zinc
γ-Aminobutyric acid A receptors
γ-Aminobutyric acid receptors
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Summary:Pancreatic islet β-cells produce large amounts of γ-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing α-cells via type-A GABA receptors (GABA(A)Rs). We and others recently reported that islet β-cells also express GABA(A)Rs and that activation of GABA(A)Rs increases insulin release. Here we investigate the effects of insulin on the GABA-GABA(A)R system in the pancreatic INS-1 cells using perforated-patch recording. The results showed that GABA produces a rapid inward current and depolarizes INS-1 cells. However, pre-treatment of the cell with regular insulin (1 µM) suppressed the GABA-induced current (I(GABA)) by 43%. Zinc-free insulin also suppressed I(GABA) to the same extent of inhibition by regular insulin. The inhibition of I(GABA) occurs within 30 seconds after application of insulin. The insulin-induced inhibition of I(GABA) persisted in the presence of PI3-kinase inhibitor, but was abolished upon inhibition of ERK, indicating that insulin suppresses GABA(A)Rs through a mechanism that involves ERK activation. Radioimmunoassay revealed that the secretion of C-peptide was enhanced by GABA, which was blocked by pre-incubating the cells with picrotoxin (50 µM, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0026225