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Using an image-based screen for small molecules that can affect Golgi morphology, we identify a small molecule, Sioc145, which can enlarge the Golgi compartments and promote protein secretion. More importantly, Sioc145 potentiates insulin secretion in a glucose-dependent manner. We show that Sioc145 selectively activates novel protein kinase Cs (nPKCs; δ and ε) but not conventional PKCs (cPKCs; α, βI and βII) in INS-1E insulinoma cells. In contrast, PMA, a non-selective activator of cPKCs and nPKCs, promotes insulin secretion independent of glucose concentrations. Furthermore, we demonstrate that Sioc145 and PMA show differential abilities in depolarizing the cell membrane, and suggest that Sioc145 promotes insulin secretion in the amplifying pathway downstream of KATP channels. In pancreatic islets, the treatment with Sioc145 enhances the second phase of insulin secretion. Increased insulin granules close to the plasma membrane are observed after Sioc145 treatment. Finally, the administration of Sioc145 to diabetic GK rats increases their serum insulin levels and improves glucose tolerance. Collectively, our studies identify Sioc145 as a novel glucose-dependent insulinotropic compound via selectively activating nPKCs.

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Glucose-induced glutathione reduction in mitochondria is involved in the first phase of pancreatic β-cell insulin secretion, ABSTRACT Glucose can acutely reduce mitochondrial glutathione redox state in rat islets.However, whether glucose-stimulated mitochondrial glutathione redox state relates to glucose-stimulated insulin secretion (GSIS) remains unknown. We used genetically encoded redox-sensitive GFPs to target the mitochondria to monitor glutathione redox changes during GSIS in rat pancreatic β-cells. The results showed that mitochondrial glutathione was more reduced during GSIS, whereas inhibition of this glutathione reduction impaired insulin secretion. In isolated rat pancreatic islets glutathione reduction in mitochondria and the first phase of GSIS were concurrence at the early stage of glucose-stimulation.Our results suggest that the glucose-induced glutathione reduction in mitochondria is primarily required for the first phase of GSIS.

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Cycloaliphatic epoxy (CE) resin plays a vital role in insulation equipment due to its excellent insulation and processability. However, the insufficient ability of CE to confine electrons under high voltage often leads to an electric breakdown, which limits its wide applications in high-voltage insulation equipment. In this work, the interface effect of inorganic nano-SiO 2 introduces deep traps to capture electrons, which is synergistic with the inherent ability of the voltage stabilizer m -aminobenzoic acid ( m -ABA) to capture high-energy electrons through collision. Therefore, the insulation failure rate is reduced owing to doping of the functionalized nanoparticles of the m -ABA-grafted nano-SiO 2 ( m -ABA-SiO 2 ) into the CE. It is worth noting that the breakdown field strength of this m -ABA-SiO 2 /CE reaches 53 kV/mm, which is 40.8% higher than that of pure CE. In addition, the tensile strength and volume resistivity of m -ABA-SiO 2 /CE are increased by 29.1 and 140%, respectively. Meanwhile, the glass transition temperature was increased by about 25 °C and reached 213 °C. This work proves that the comprehensive performance of CE-based nanocomposites is effectively improved by m -ABA-SiO 2 nanoparticles, showing great application potential in high-voltage insulated power equipment.