Details

Autor(en) / Beteiligte

• Bailey, Sarah J
• Ravier, Magalie A
• Rutter, Guy A

Titel

Glucose-dependent regulation of [gamma]-aminobutyric acid receptor expression in mouse pancreatic islet [alpha]-cells

Ist Teil von

• Diabetes (New York, N.Y.), 2007-02, Vol.56 (2), p.320

Ort / Verlag

New York: American Diabetes Association

Erscheinungsjahr

2007

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The mechanism(s) by which glucose regulates glucagon secretion both acutely and in the longer term remain unclear. Added to isolated mouse islets in the presence of 0.5 mmol/l glucose, [gamma]-aminobutyric acid (GABA) inhibited glucagon release to a similar extent (46%) as 10 mmol/l glucose (55%), and the selective [GABA.sub.A] receptor ([GABA.sub.A]R) antagonist SR95531 substantially reversed the inhibition of glucagon release by high glucose. [GABA.sub.A]R [alpha]4, [beta]3, and [gamma]2 subunit mRNAs were detected in mouse islets and clonal [alpha]TC1-9 cells, and immunocytochemistry confirmed the presence of [GABA.sub.A]RS at the plasma membrane of primary a-cells. Glucose dose-dependently increased [GABA.sub.A]R expression in both islets and [alpha]TC1-9 cells such that mRNA levels at 16 mmol/l glucose were ~3.0-fold ([alpha]4), 2.0-fold ([beta]3), or 1.5-fold ([gamma]2) higher than at basal glucose concentrations (2.5 or 1.0 mmol/l, respectively). These effects were mimicked by depolarizing concentrations of [K.sup.+] and reversed by the L-type [Ca.sup.2+] channel blocker nimodipine. We conclude that 1) release of GABA from neighboring [beta]-cells contributes substantially to the acute inhibition of glucagon secretion from mouse islets by glucose and 2) that changes in [GABA.sub.A]R expression, mediated by changes in intracellular free [Ca.sup.2+] concentration, may modulate this response in the long term. Diabetes 56: 320-327, 2007