Diabetes

As a key regulator of whole body metabolism, the hormone insulin is secreted by pancreatic β-cells as a response to an elevation in nutrients. Insulin facilitates the conversion of glucose into liver- and muscle-glycogen, as well as the uptake of amino acids in cells.

Not just glucose, but also amino acids (protein) directly trigger the release of insulin (eg glycine [1], arginine [2], leucine, isoleucine, valine [3], aspartic acid, alanine and serine [4]). Amino acids affect glucose uptake and compete as oxidative fuels.[5] Lysine, tyrosine, alanine, serine and aspartic acid may play a key role in glucose-stimulated insulin secretion.[6] In pancreatic islets from both healthy young children and adults, insulin secretion is stimulated by arginine and the combination of leucine and glutamine, concentration-dependent and in an biphasic pattern, similarly to glucose-induced insulin secretion.[7] Dysregulated leucine metabolism progressively develops into insulin resistance.[8]

Insulin resistance is related to valine, glutamate, tyrosine, glutamine and glycine levels. β-cell functioning is related to leucine, tryptophan, valine, glutamate, glutamine, glycine and serine levels.[9] A mixture of leucine, isoleucine, valine, lysine and threonine resulted in significant glycemic and insulinemic responses.[10] Insulin responses are positively correlated with plasma leucine, phenylalanine, and tyrosine concentrations.[11]

In a 12-year follow-up study involving adult Japanese individuals, plasma levels of isoleucine, leucine, valine, tyrosine, and phenylalanine (particularly any combination of minimally 3 of these amino acids) were reported to predict the development of diabetes in nondiabetic subjects.[12] Obese women show a blunted protein anabolic response to hyperinsulinemia that is consistent with resistance to the action of insulin on protein concurrent with that on glucose metabolism.[13]

Overweight Pathway

Obesity is a leading pathogenic factor for developing insulin resistance.[14]

Protein Pathway

A diet that is low in AGEs (see Maillard Reaction) may reduce the risk of type 2 diabetes by increasing insulin sensitivity.[15] This may be due to the longer retention time of AGEs versus non-glycated amino acids and peptides.