NMDA Suppresses Pancreatic ABCA1 Expression through the MEK/ERK/LXR Pathway in Pancreatic Beta Cells.

Dysfunction or loss of pancreatic ß cells can cause insulin deficiency and impaired glucose regulation, resulting in conditions like type 2 diabetes. The ATP-binding cassette transporter A1 (ABCA1) plays a key role in the reverse cholesterol transport system, and its decreased expression is associated with pancreatic ß cell lipotoxicity, resulting in abnormal insulin synthesis and secretion. Increased glutamate release can cause glucotoxicity in ß cells, though the detailed mechanisms remain unclear. This study investigated the effect of N-methyl-D-aspartic acid (NMDA) on ABCA1 expression in INS-1 cells and primary pancreatic islets to elucidate the signaling mechanisms that suppress insulin secretion. Using Western blotting, microscopy, and biochemical analyses, we found that NMDA activated the mitogen-activated protein kinase (MEK)-dependent pathway, suppressing ABCA1 protein and mRNA expression. The MEK-specific inhibitor PD98059 restored ABCA1 promoter activity, indicating the involvement of the extracellular signal-regulated kinase (MEK/ERK) pathway. Furthermore, we identified the liver X receptor (LXR) as an effector transcription factor in NMDA regulation of ABCA1 transcription. NMDA treatment increased cholesterol and triglyceride levels while decreasing insulin secretion, even under high-glucose conditions. These effects were abrogated by treatment with PD98059. This study reveals that NMDA suppresses ABCA1 expression via the MEK/ERK/LXR pathway, providing new insights into the pathological suppression of insulin secretion in pancreatic ß cells and emphasizing the importance of investigating the role of NMDA in ß cell dysfunction.

A Pilot Study on the Efficacy of a Diabetic Diet Containing the Rare Sugar D-Allulose in Patients with Type 2 Diabetes Mellitus: A Prospective, Randomized, Single-Blind, Crossover Study.

High sugar consumption increases the risk of diabetes, obesity, and cardiovascular diseases. Regarding the diet of patients with diabetes, artificial sweeteners are considered a safe alternative to sugar; however, there is also a risk that artificial sweeteners exacerbate glucose metabolism. D-allulose (C-3 isomer of d-fructose), which is a rare sugar, has been reported to have antidiabetic and antiobesity effects. In this study, the efficacy of a diabetic diet containing D-allulose was investigated in patients with type 2 diabetes using an intermittently scanned continuous glucose monitoring system (isCGM). This study was a validated, prospective, single-blind, randomized, crossover comparative study. Comparison of peak postprandial blood glucose (PPG) levels after consumption of a standard diabetic diet and a diabetic diet containing 8.5 g of D-allulose was the primary endpoint. A D-allulose-containing diabetic diet improved PPG levels in type two diabetes patients compared with a strictly energy-controlled diabetic diet. The results also showed a protective effect on endogenous pancreatic insulin secretory capacity owing to reduced insulin requirement. In patients with type two diabetes mellitus, diabetic diets containing 8.5 g D-allulose were effective in improving PPG levels.