The stimulus–secretion coupling of amino acid-induced insulin release. Insulinotropic action of ?-alanine

Sener, Abdullah; Malaisse, Willy

doi:10.1016/s0304-4165(02)00337-9

Cited by 37 publications

(22 citation statements)

References 17 publications

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“…However, in the presence of L-leucine or 2-ketoisocaproate, alanine promoted insulin secretion (59). Additionally, L-alanine induced an increase in Ca 2ϩ uptake and was oxidized by the ␤-cell.…”

Section: Mechanisms Of Amino Acid-dependent Stimulation Of Insulin Sementioning

confidence: 96%

Amino Acid Metabolism, β-Cell Function, and Diabetes

2006

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Specific amino acids are known to acutely and chronically regulate insulin secretion from pancreatic ␤-cells in vivo and in vitro. Mitochondrial metabolism is crucial for the coupling of amino acid and glucose recognition to exocytosis of 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 messenger in insulin secretion, and other coupling factors, which serve as sensors for the control of the exocytotic process. Numerous studies have sought to identify the factors that mediate the key amplifying pathway over the Ca 2؉ signal in nutrient-stimulated insulin secretion. Predominantly, these factors are nucleotides (ATP, GTP, cAMP, and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and glutamate. This scenario further highlights the importance of the key enzymes or transporters, e.g., glutamate dehydrogenase, the aspartate and alanine aminotransferases, and the malate-aspartate shuttle in the control of insulin secretion. In addition, after chronic exposure, amino acids may influence gene expression in the ␤-cell, which subsequently alters levels of insulin secretion. Therefore, amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion. Diabetes 55 (Suppl. 2)

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Section: Mechanisms Of Amino Acid-dependent Stimulation Of Insulin Sementioning

confidence: 96%

Amino Acid Metabolism, β-Cell Function, and Diabetes

2006

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“…-alanine metabolism for example, is known to enhance insulin secretion alone or synergistically enhance glucosestimulated insulin secretion from the clonal beta-cell line BRIN-BD11 (Brennan et al 2002). Other investigators, however, have not demonstrated an insulinotropic effect of -alanine when added to rat islet cells (Sener & Malaisse 2002). -glutamine while readily consumed by beta-cells does not stimulate insulin secretion in the absence of allosteric activation of glutamate dehydrogenase (GDH).…”

Section: Introductionmentioning

confidence: 97%

A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine

Dixon¹,

Nolan²,

McClenaghan³

et al. 2003

Journal of Endocrinology

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Evidence has been published that -alanine may, under appropriate conditions, promote insulin secretion in normal rodent islets and various beta cell lines. Previous results utilising the clonal beta-cell line BRIN-BD11, demonstrated that alanine dramatically elevated insulin release by a mechanism requiring oxidative metabolism. We demonstrate in this paper that addition of -alanine had an insulinotropic effect in dispersed primary islet cells. Addition of -glucose increased -alanine consumption in both BRIN-BD11 cells and primary islet cells.-glutamine consumption in the BRIN-BD11 cell line and primary rat islets was also determined. The consumption rate was in line with that previously reported for cells of the immune system and other glutamine-utilising cells or tissues. However, -alanine consumption was at least an order of magnitude higher than -glutamine consumption. The metabolism of -alanine in the beta-cell may result in stimulation of insulin secretion via generation of metabolic stimulus secretion coupling factors such as -glutamate.

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“…85 Besides complete mixtures of all 20 amino acids, certain individual amino acids, including alanine, asparagine, glycine, glutamate, phenylalanine, and tryptophan, can potentiate GSIS. [86][87][88][89] As shown in Figure 6A, a ramp perifusion of a physiological mixture of 19 amino acids (AAM) strongly potentiated 10 mM glucose-stimulated insulin secretion in isolated wild-type mouse islets. Figure 6A also shows that AAM alone cannot stimulate insulin secretion in wild-type mouse islets.…”

Section: Amino Acid-potentiated Gsis and Glucose-dependent Amino Acidmentioning

confidence: 94%

Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes

Lü

2017

Annals of the New York Academy of Sciences

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Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM)). Mutations of beta cell ion channels involved in insulin secretion regulation also alter glucose sensing. Activating or inactivating mutations of ATPdependent potassium (K ATP ) channel genes result in severe but completely opposite clinical phenotypes, including PNDM and CHI. Mutations of the other ion channels, including voltage-gated potassium channels (K v 7.1) and voltage-gated calcium channels, also lead to abnormal glucose sensing and CHI. Furthermore, amino acids can stimulate insulin secretion in a glucose-independent manner in some forms of CHI, including activating mutations of the glutamate dehydrogenase gene, HDAH deficiency, and inactivating mutations of K ATP channel genes. These genetic defects have provided insight into a better understanding of the complicated nature of beta cell fuel-sensing mechanisms.

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The stimulus–secretion coupling of amino acid-induced insulin release. Insulinotropic action of ?-alanine

Cited by 37 publications

References 17 publications

Amino Acid Metabolism, β-Cell Function, and Diabetes

Amino Acid Metabolism, β-Cell Function, and Diabetes

A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine

Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes

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