Abstract
To determine if endogenous gamma-aminobutyric acid (GABA) is secreted by a pancreatic beta-cell-derived cell line and to determine the effects of glucose on GABA release, beta TC6 cultures were incubated in the presence of 1 or 10 mmol/l glucose for 12 h and then subjected to a 2-h secretion test in Krebs-Ringer buffer containing 1 or 10 mmol/l glucose. beta TC6-conditioned medium was collected at 15, 30, 60, and 120 min after glucose stimulation for GABA analysis by high pressure liquid chromatography-electrochemical detection. After 30 min, medium GABA concentrations were significantly higher (p < 0.05) in cultures that were exposed to high glucose during both the 12-h incubation period and the 2-h secretion test than in the remaining three glucose combinations. To address possible roles of beta-cell-derived GABA, the effect of GABA on glucagon secretion from pancreatic alpha TC6 cells was tested at concentrations released from beta TC6 cells. Inhibition of glucagon secretion by alpha TC6 cells was observed in the presence of GABA at concentrations equivalent to concentrations secreted by beta TC6 cells. The inhibitory effects of GABA on glucagon secretion by alpha TC6 cells were blocked by the GABAA receptor antagonist bicuculline and were dissociated from the inhibitory effects of glucose. Together, these results provide the first documentation that endogenous GABA is released from a highly differentiated beta-cell line and that glucose and GABA independently attenuate glucagon secretion by a pancreatic alpha-cell line.
Highlights
Ʈ Recipient of a summer scholarship from the Ronald E
Effect of Extracellular Glucose Concentrations on GABA Secretion by TC6 Cells—Nanomolar concentrations of GABA were recovered in TC6-conditioned medium at all time points (15 min, 30 min, 1 h, 2 h) throughout a 2-h secretion test for both the low (1.0 mmol/l) and high (10 mmol/l) glucose treatments (Fig. 1)
At all time points thereafter (30, 60, and 120 min), GABA concentrations in the medium were significantly greater (p Ͻ 0.05) in cultures that were exposed to high glucose during both the 12-h incubation period and during the 2-h secretion period than in any of the remaining three glucose combinations (1:1, 1:10, and 10:1 mmol/l glucose; Fig. 1)
Summary
Ʈ Recipient of a summer scholarship from the Ronald E. In the present study, differentiated pancreatic ␣- and -cell lines derived from transgenic mice [15, 16] were used to determine (i) if GABA is released from transformed -cells, (ii) if GABA secretion is influenced by extracellular glucose concentrations, and (iii) to test the effects of GABA on glucagon secretion from a purified ␣-cell line. Glucose concentrations during the 12-h culture period and during the 2-h secretion test independently influenced GABA concentrations in TC6-conditioned medium.
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