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The endoplasmic reticulum (ER) is the site of protein production and relies heavily on Ca 2+ concentrations to maintain the environment needed for proper protein synthesis and folding ( Figure 2A ) ( Figure 2F ) ( via the glucose transporter 2 (Glut2) in rodents (GLUT1 and 3 in humans), converted to pyruvate, and shuttled into the mitochondria where it is used for ATP production ( 2+ influx, and insulin release ( Insulin mRNA is translated at the ER following nutrient stimulation, which in rodents can signal up to a 10-fold increase in insulin synthesis at a rate of 1 million molecules per minute ( Figure 2 To meet these high demands, beta-cells have an extensive ER with multiple chaperones to aid in protein folding, packaging, and secretion