Figure 4

Effect of experimental alteration of pH _i on direct insulin secretion by mitochondrial secretagogues: Insulin secretion from freshly isolated islets, in response to different secretagogues as indicated, with and without intracellular pH altered. Controls are in 2.8 mM and 16.7 mM glucose, and test groups are in leucine, αKIC or BCH, 20 mM each. Intracellular acidification was produced by 40 μM DMA. Intracellular alkalinization was produced by either a Cl^--free medium (A), a high pH (>8.3) medium (A), or a combination of both (B-D). All groups were first pre-incubated in basal glucose for one hour, and subsequently exposed to each condition denoted in the X axes for one hour, followed by sample collection for insulin assay. Insulin secretion is expressed as fractional release %, i.e. the percentage of the total insulin content released over the one-hour period of stimulation with different agents. G = mM glucose; Leu = leucine. A) Glucose: n = 6; * = p < 0.001; and † = p < 0.05, compared to stimulated control in high glucose without pH_i-alteration. B) Leucine: n = 5; * = p < 0.001, and † = p < 0.05, compared to leucine without pH_i-alteration. C) BCH: n = 5; * = p < 0.001, compared to BCH without pH_i-alteration. D) αKIC: n = 8; * = p < 0.001, and † = p < 0.05, compared to αKIC without pH_i-alteration.