Diabetes

Insulin Secretion

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 (and fatty acids), but also amino acids (protein) directly trigger the release of insulin (eg glycine [1], arginine [2], leucine [3], isoleucine, valine [4], aspartic acid, alanine and serine [5]). Amino acids also affect glucose uptake (particularly phenylalanine [6]) and compete as oxidative fuels.[7] Lysine, tyrosine, alanine, serine and aspartic acid may play a key role in glucose-stimulated insulin secretion.[8] 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.[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]

Insulin Resistance

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.[12] Dysregulated leucine metabolism progressively develops into insulin resistance [13], and high leucine exposure induced insulin resistance may be reversed by removing the high leucine exposure.[14] 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.[15]

Overweight Pathway

Obesity is a leading pathogenic factor for developing insulin resistance.[16] 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.[17] Insulin evokes the storage of blood glucose as liver glycogen. Once liver glycogen is completely repleted, additional blood glucose needs to be stored as glycerol in triglycerides. The latter is a relatively slow process, which can give way to repeated triggering of insulin release, which may lead to insulin resistance.

Protein Pathway

A diet that is low in AGEs (see Maillard Reaction) may reduce the risk of type 2 diabetes by increasing insulin sensitivity.[18] This may be due to the longer half-life of AGEs versus non-glycated amino acids and peptides.