Protective Effects of Imeglimin and Metformin Combination Therapy on ß-Cells in db/db Male Mice.

Imeglimin and metformin act in metabolic organs, including ß-cells, via different mechanisms. In the present study, we investigated the impacts of imeglimin, metformin, or their combination (Imeg + Met) on ß-cells, the liver, and adipose tissues in db/db mice. Imeglimin, metformin, or Imeg + Met treatment had no significant effects on glucose tolerance, insulin sensitivity, respiratory exchange ratio, or locomotor activity in db/db mice. The responsiveness of insulin secretion to glucose was recovered by Imeg + Met treatment. Furthermore, Imeg + Met treatment increased ß-cell mass by enhancing ß-cell proliferation and ameliorating ß-cell apoptosis in db/db mice. Hepatic steatosis, the morphology of adipocytes, adiposity assessed by computed tomography, and the expression of genes related to glucose or lipid metabolism and inflammation in the liver and fat tissues showed no notable differences in db/db mice. Global gene expression analysis of isolated islets indicated that the genes related to regulation of cell population proliferation and negative regulation of cell death were enriched by Imeg + Met treatment in db/db islets. In vitro culture experiments confirmed the protective effects of Imeg + Met against ß-cell apoptosis. The expression of Snai1, Tnfrsf18, Pdcd1, Mmp9, Ccr7, Egr3, and Cxcl12, some of which have been linked to apoptosis, in db/db islets was attenuated by Imeg + Met. Treatment of a ß-cell line with Imeg + Met prevented apoptosis induced by hydrogen peroxide or palmitate. Thus, the combination of imeglimin and metformin is beneficial for the maintenance of ß-cell mass in db/db mice, probably through direct action on ß-cells, suggesting a potential strategy for protecting ß-cells in the treatment of type 2 diabetes.

Pulsation Reduction Using Dual Sidewall-Driven Micropumps.

Single-cell manipulation in microfluidic channels at the micrometer scale has recently become common. However, the current mainstream method using a syringe pump and a piezoelectric actuator is not suitable for long-term experiments. Some methods incorporate a pump mechanism into a microfluidic channel, but they are not suitable for mass production owing to their complex structures. Here, we propose a sidewall-driven micropump integrated into a microfluidic device as well as a method for reducing the pulsation of flow. This sidewall-driven micropump consists of small chambers lined up on both sides along the main flow path, with a wall separating the flow path and each chamber being deformed by air pressure. The chambers are pressurized to make the peristaltic motion of the wall possible, which generates flow in the main flow path. This pump can be created in a single layer, which allows a simplified structure to be achieved, although pulsation can occur when the pump is used alone. We created two types of chips with two micropumps placed in the flow path and attempted to reduce pulsation by driving them in different phases. The proposed dually driven micropump reduced pulsation when compared with the single pump. This device enables precise particle control and is expected to contribute to less costly and easier cell manipulation experiments.