New insights into amino acid metabolism, β-cell function and diabetes

Abstract

Specific amino acids are now known to acutely and chronically regulate insulin secretion from pancreatic beta-cells in vivo and in vitro. Understanding the molecular mechanisms by which amino acids regulate insulin secretion may identify novel targets for future diabetes therapies. Mitochondrial metabolism is crucial for the coupling of amino acid and glucose recognition to the exocytosis of the insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP, which is the main coupling factor in insulin secretion; however, the subsequent Ca2+ signal in the cytosol is necessary, but not sufficient, for full development of sustained insulin secretion. Hence mitochondria generate ATP and other coupling factors serving as fuel sensors for the control of the exocytotic process. Numerous studies have sought to identify the factors that mediate the amplifying pathway over the Ca2+ signal in nutrient-stimulated insulin secretion. Predominantly, these factors are nucleotides (GTP, ATP, cAMP and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and the key amino acid glutamate. This scenario highlights further the importance of the key enzymes or transporters, glutamate dehydrogenase, the aspartate and alanine aminotransferases and the malate/aspartate shuttle, in the control of insulin secretion. Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion.

Protein hydrolysate co-ingestion does not modulate 24 h glycemic control in long-standing type 2 diabetes patients

“…Both in vivo and in vitro work has identified leucine as a particularly interesting insulin secretagogue, as leucine both induces and enhances pancreatic b-cell insulin secretion and could also help to maintain b-cell mass (Xu et al, 2001;Nair and Short, 2005;Newsholme et al, 2005). As such, leucine co-ingestion has been suggested as an effective strategy to further augment the insulinotropic effects of protein co-ingestion.…”

The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects

“…The effect of proteins on insulin secretion is mainly a consequence of the effect that specific amino acids in the blood have on pancreatic b-cell activity (Newsholme et al, 2005).…”

The effect of arginine dietary supplementation in broiler breeder hens on offspring humoral and cell-mediated immune responses

“…Arginine is required for the synthesis of several compounds, such as ornithine, polyamines, proline, creatine, proteins, nitric oxide (NO) and citrulline, and it is also considered a powerful secretagogue, increasing the release of insulin, growth hormone (GH) and insulin-like growth factor (IGF-I) into the blood stream (Newsholme et al, 2005). This action is a consequence of the rapid depolarization of the cell membrane associated with the transport of amino acids with positive side chains.…”