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Introduction Insulin is a vital hormone with several functions among which its central role in energy and glucose homeostasis is fundamental ( First reports of insulin actions in the kidney were originated in the 1950s ( Kidney is, in fact, the most critical organ responsible for insulin clearance after the liver ( Overview of Insulin Biosynthesis and Non-Renal Action and Metabolism The insulin gene ( INS ) is represented by only one copy in the human genome, and its transcription is mainly regulated by the same enhancers of other glucose-related genes ( INS is first transcribed as preproinsulin and, after cleavage and folding in the rough endoplasmic reticulum (ER), proinsulin is formed ( Insulin secretion is triggered by cytoplasmic increments in ATP levels, derived from glucose internalization and subsequent metabolism ( + channels, depolarizing plasma membrane, and activating voltage-gated calcium channels ( 2+ influx seems to be necessary for the fusion of insulin granules with the plasma membrane, ending up in its secretion ( With the insulin pools ready to be released, insulin secretion does not occur in a constant manner, but in waves of 45 min interval ( At cellular level, insulin mostly relies on the specific bind to its transmembrane receptor to perform its actions (Figure 1)