Drp1 Overexpression Decreases Insulin Content in Pancreatic MIN6 Cells

Mitochondrial dynamics and bioenergetics are central to glucose-stimulated insulin secretion by pancreatic beta cells. Previously, we demonstrated that a disturbance in glucose-invoked fission impairs insulin secretion by compromising glucose catabolism. Here, we investigated whether the overexpression of mitochondrial fission regulator Drp1 in MIN6 cells can improve or rescue insulin secretion. Although Drp1 overexpression slightly improves the triggering mechanism of insulin secretion of the Drp1-knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of Drp1 unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in Drp1-overexpressing muscle cells, we found that the upregulation of ER stress-related genes (BiP, Chop, and Hsp60) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of Drp1 for the energy-coupling of insulin secretion but unravel off-targets effects by Drp1 overexpression on insulin content that warrant caution when manipulating Drp1 in disease therapy

Arrested States formed on Quenching Spin Chains with Competing Interactions and Conserved Dynamics

We study the effects of rapidly cooling to T = 0 a spin chain with conserved dynamics and competing interactions. Depending on the degree of competition, the system is found to get arrested in different kinds of metastable states. The most interesting of these has an inhomogeneous mixture of interspersed active and quiescent regions. In this state, the steady-state autocorrelation function decays as a stretched exponential $\sim \exp(-{(t/\tau_{o})}^{{1}\over{3}})$, and there is a two-step relaxation to equilibrium when the temperature is raised slightly.Comment: 4 pages, Latex, 3 postscript figures. Phys. Rev. E to appear (1999

Direct Substrate Delivery into Mitochondrial-Fission Deficient Pancreatic Islets Rescues Insulin Secretion

In pancreatic beta cells, mitochondrial bioenergetics control glucose-stimulated insulin secretion (GSIS). Mitochondrial dynamics are generally associated with quality control, maintaining the functionality of bioenergetics. By acute pharmacological inhibition of mitochondrial fission protein Drp1, we here demonstrate that mitochondrial fission is necessary for GSIS in mouse and human islets. We confirm that genetic silencing of Drp1 increases mitochondrial proton leak in MIN6 cells. However, our comprehensive analysis of pancreatic islet bioenergetics reveals that Drp1 does not control insulin secretion via its effect on proton leak but instead via modulation of glucose-fuelled respiration. Notably, pyruvate fully rescues the impaired insulin secretion of fission-deficient beta cells, demonstrating that defective mitochondrial dynamics solely impact substrate supply upstream of oxidative phosphorylation. The present findings provide novel insights in how mitochondrial dysfunction may cause pancreatic beta cell failure. In addition, the results will stimulate new thinking in the intersecting fields of mitochondrial dynamics and bioenergetics, as treatment of defective dynamics in mitochondrial diseases appears to be possible by improving metabolism upstream of mitochondria

Benzothiazol-2-yl-hydrazone derivatives as potential antioxidant agents

A series of benzothiazol-2-yl-hydrazone derivatives (4a-i) have been synthesized and characterized using elemental analysis, FT-IR, 1H-NMR and Mass spectroscopy techniques. The synthesized compounds have been screened for antioxidant activity by DPPH radical scavenging activity method. The compounds bearing methoxy substitution4c, 4e, 4f, 4g, 4h and 4i have shown promising antioxidant activity, better than the standard drug ascorbic acid

Sustainability Assessment of Chemical Processes: Evaluation of Three Synthesis Routes of DMC

This paper suggested multicriteria based evaluation tool to assess the sustainability of three different reaction routes to dimethyl carbonate: direct synthesis from carbon dioxide and methanol, transesterification of methanol and propylene carbonate, and oxidative carbonylation of methanol. The first two routes are CO 2 -based and in a research and development phase, whereas the last one is a commercial process. The set of environmental, social, and economic indicators selected were renewability of feedstock, energy intensity, waste generation, CO 2 balance, yield, feedstock price, process costs, health and safety issues of feedstock, process conditions, and innovation potential. The performance in these indicators was evaluated with the normalized scores from 0 to +1; 0 for detrimental and 1 for favorable impacts. The assessment showed that the transesterification route had the best potential toward sustainability, although there is still much development needed to improve yield. Further, the assessment gave clear understanding of the main benefits of each reaction route, as well as the major challenges to sustainability, which can further aid in orienting development efforts to key issues that need improvement. Finally, it was concluded that a multicriteria analysis such as the one presented in this paper was a viable method to be used in the process design stage