Figure 6

Effect of experimental alteration of pH _i on insulin secretion by non-mitochondrial secretagogues: A. Insulin secretion by high K⁺ is not significantly influenced by pH_i-alteration: Insulin secretion in response 50 mM K⁺ with and without pH_i-alteration techniques (40 μM DMA for acidification and a Cl^--free high pH medium for alkalinization) from freshly isolated islets. Control groups were exposed to 2.8 mM and 16.7 mM glucose. All groups were first pre-incubated in basal glucose for one hour, and subsequently exposed to each condition denoted in the X axis 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. n = 7; G = mM glucose. B. GSIS is inhibited by AOA and CHC. This inhibition is reversed by DMA: Insulin secretion in response to glucose combined with AOA and CHC (5 mM each) in the presence or absence of 40 μM DMA, from freshly isolated islets. All groups were first pre-incubated in basal glucose for one hour, and subsequently exposed to each condition denoted in the X axis 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. n = 5; * = p < 0.001, compared with high glucose alone, or with high glucose with inhibitors and DMA added.