ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment

Glucagon-like peptide-1 (GLP-1) is a well-known incretin hormone secreted from enteroendocrinal L cells in response to nutrients, such as glucose and dietary fat, and controls glycemic homeostasis. However, the detailed intracellular mechanisms of how L cells control GLP-1 secretion in response to nutrients still remain unclear. Here, we report that bone morphogenetic protein (BMP) signaling pathway plays a pivotal role to control GLP-1 secretion in response to nutrient replenishment in well-established mouse enteroendocrinal L cells (GLUTag cells). Nutrient starvation dramatically reduced cellular respiration and GLP-1 secretion in GLUTag cells. Transcriptome analysis revealed that nutrient starvation remarkably reduced gene expressions involved in BMP signaling pathway, whereas nutrient replenishment rescued BMP signaling to potentiate GLP-1 secretion. Transient knockdown of inhibitor of DNA binding (ID)1, a well-known target gene of BMP signaling, remarkably reduced GLP-1 secretion. Consistently, LDN193189, an inhibitor of BMP signaling, markedly reduced GLP-1 secretion in L cells. In contrast, BMP4 treatment activated BMP signaling pathway and potentiated GLP-1 secretion in response to nutrient replenishment. Altogether, we demonstrated that BMP signaling pathway is a novel molecular mechanism to control GLP-1 secretion in response to cellular nutrient status. Selective activation of BMP signaling would be a potent therapeutic strategy to stimulate GLP-1 secretion in order to restore glycemic homeostasis.

Theoretical and Experimental Analysis of Nutrient Variations in Electrical Conductivity-Based Closed-Loop Soilless Culture Systems by Nutrient Replenishment Method

In closed-loop soilless culture systems, variation in nutrients can lead to instability in the nutrient management and forced discharge of nutrients and water. Total nutrients absorbed by plants are replenished in an electrical conductivity-based closed-loop system, and fluctuation in electrical conductivity within a certain range around the initial value can be expected. However, this is not always observed in systems using conventional nutrient-replenishment methods. The objectives of this study were to analyze nutrient variation in a closed-loop soilless culture system based on a theoretical model and derive an alternative nutrient-replenishment method. The performance of the derived alternative method was compared with a conventional nutrient-replenishment method through simulation analysis. A demonstration experiment using sweet peppers was then conducted to confirm whether the theoretical analysis results can be reproduced through actual cultivation. The average amounts of injected nutrients during the experimental period of four months in the conventional and alternative methods were 2257 and 1054 g, respectively. There was no significant difference in the yield of sweet peppers between the two methods. The substrate electrical conductivity in the alternative method was maintained at 2.7 dS⋅m−1 ± 0.5 within the target electrical conductivity value, while that in the conventional method gradually increased to 5.0 dS⋅m−1 ± 1.2. In a simulation study, results similar to the demonstration experiment were predicted. Total nutrient concentrations in the alternative method showed fluctuations around the target value but did not continuously deviate from the target value, while those in the conventional method showed a tendency to increase. As a whole, these characteristics of the alternative method can help in minimizing nutrients and water emissions from the cultivation system.