Insulin

Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues throughout the human body. ^[1] Insulin resistance and hyperhormonaemia, including elevated insulin, are non-disputable hallmarks of type 2 diabetes and can already be present in normoglycaemic, otherwise healthy subjects. ^[2]

Insulin resistance is characterized by defects in the uptake and oxidation of glucose, a decrease in glycogen synthesis, and a reduced ability to suppress lipid oxidation. ^[1] Beyond glucose, insulin regulates serum VLDL concentrations by suppressing hepatic VLDL production and stimulating VLDL removal via lipoprotein lipase, linking insulin to atherogenic dyslipidaemia. ^[3] Hyperinsulinaemia can precede insulin resistance rather than always following it, and other drivers such as high androgen levels can augment both, as seen in polycystic ovary syndrome. ^[4] Insulin signaling operates alongside the growth hormone and IGF-1 axis, and modulation of insulin, IGF-1, and growth hormone is thought to partly mediate the cancer-preventive effects of calorie restriction and fasting-based dietary interventions ^[5] Insulin is a principal upstream signal activating mTOR, which integrates hormonal, amino acid, energy, and oxygen inputs to coordinate protein synthesis, autophagy, cell growth, and proliferation ^[6]