Stimulus-secretion coupling of arginine-induced insulin release. Functional response of islets to l-arginine and l-ornithine

Blachier, François; Leclercq‐Meyer, V.; Marchand, J.; Woussen-Colle, M.C.; Mathias, Paulo Cézar de Freitas; Sener, Abdullah; Malaisse, Willy

doi:10.1016/0167-4889(89)90042-6

Cited by 66 publications

(32 citation statements)

References 20 publications

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“…Further research in the intact animal will be required to assess the physiological relevance of this regulatory mechanism. The action of amino acids described here seems rather similar, both in substrate preferences and in mechanisms, to that reported previously in pancreatic â-cells (Malaisse, 1972;Blachier et al 1989;Drews & Krippeitdrews, 1995;Ashcroft et al 1995). Thus, electrogenic amino acid transport might act as a general mechanism for linking the nutritional andÏor metabolic status with regulation of hormone release in secretory cells possessing voltage-gated Ca¥ channels.…”

Section: Discussionsupporting

confidence: 61%

“…Membrane depolarization also seems the most likely mechanism to explain the increase in Ca¥ entry observed here. The depolarization induced by arginine and other amino acids in pancreatic â-cells (Blachier et al 1989;Drews & Krippeitdrews, 1995;Aschroft, Coles, Gummerson, Sakura & Smith, 1995) and the increase in [Ca¥]é induced by glutamate and other acidic amino acids in GH× pituitary cells (Villalobos & Garc úa-Sancho, 1995a) have both been attributed to electrogenic amino acid entry. We find that the [Ca¥]é-increasing effect of amino acids in AP cells is dependent on external Na¤, suggesting that it may require the operation of a Na¤-dependent transport system.…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids

Alonso

Núñez

García‐Sancho

1997

The Journal of Physiology

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Arginine and other amino acids are secretagogues for growth hormone and prolactin in the intact animal, but the mechanism of action is unclear. We have studied the effects of amino acids on cytosolic free calcium concentration ([Ca2+]i) in single rat anterior pituitary (AP) cells. Arginine elicited a large increase of [Ca2+]i in about 40 % of all the AP cells, suggesting that amino acids may modulate hormone secretion by acting directly on the pituitary. Cell typing by immunofluorescence of the hormone the cells store showed that the arginine‐sensitive cells are distributed uniformly within all the five AP cell types. The arginine‐sensitive cells overlapped closely with the subpopulation of cells sensitive to thyrotrophin‐releasing hormone. Other cationic as well as several neutral (dipolar) amino acids had the same effect as arginine. The increase of [Ca2+]i was dependent on extracellular Ca2+ and blocked by dihydropyridine, suggesting that it is due to Ca2+ influx through l‐type voltage‐gated Ca2+ channels. The [Ca2+]i increase was also blocked by removal of extracellular Na+ but not by tetrodotoxin. The substrate specificity for stimulation of AP cells resembled closely that of the amino acid transport system B0,+. We propose that electrogenic amino acid influx through this pathway depolarizes the plasma membrane with the subsequent activation of voltage‐gated Ca2+ channels and Ca2+ entry. Amino acids also stimulated prolactin secretion in vitro with a similar substrate specificity to that found for the [Ca2+]i increase. Existing data on the stimulation of secretion of other hormones by amino acids suggest that a similar mechanism could apply to other endocrine glands.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids

Alonso

Núñez

García‐Sancho

1997

The Journal of Physiology

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“…Fatty acids (FA) also increase insulin secretion by increasing FA ␤-oxidation leading to a high ATP/ADP ratio or by activating some protein kinases (19 -21). On the other hand, some amino acids such as arginine, alanine, glutamine, and glycine modify the membrane potential, opening the voltage-sensitive calcium channels, and increasing insulin secretion (22)(23)(24). Interestingly, the isoflavones, genistein and daidzein, the main phytoestrogens present in soy protein, also modify insulin secretion.…”

mentioning

confidence: 99%

Pancreatic Insulin Secretion in Rats Fed a Soy Protein High Fat Diet Depends on the Interaction between the Amino Acid Pattern and Isoflavones

Noriega

Tovar²,

González‐Granillo

et al. 2007

Journal of Biological Chemistry

100

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Obesity is frequently associated with the consumption of high carbohydrate/fat diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP) reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose of the present work was to establish whether SP stimulates insulin secretion to a lower extent and/or reduces insulin resistance, and to understand its molecular mechanism of action in pancreatic islets of rats with diet-induced obesity. Long-term consumption of SP in a high fat (HF) diet significantly decreased serum glucose, free fatty acids, leptin, and the insulin:glucagon ratio compared with animals fed a casein HF diet. Hyperglycemic clamps indicated that SP stimulated insulin secretion to a lower extent despite HF consumption. Furthermore, there was lower pancreatic islet area and insulin, SREBP-1, PPAR␥, and GLUT-2 mRNA abundance in comparison with rats fed the casein HF diet. Euglycemic-hyperinsulinemic clamps showed that the SP diet prevented insulin resistance despite consumption of a HF diet. Incubation of pancreatic islets with isoflavones reduced insulin secretion and expression of PPAR␥. Addition of amino acids resembling the plasma concentration of rats fed casein stimulated insulin secretion; a response that was reduced by the presence of isoflavones, whereas the amino acid pattern resembling the plasma concentration of rats fed SP barely stimulated insulin release. Infusion of isoflavones during the hyperglycemic clamps did not stimulate insulin secretion. Therefore, isoflavones as well as the amino acid pattern seen after SP consumption stimulated insulin secretion to a lower extent, decreasing PPAR␥, GLUT-2, and SREBP-1 expression, and ameliorating hyperinsulinemia observed during obesity.Obesity is a major health problem around the world because of chronic overnutrition and increase in the sedentary life style (1, 2). The development of obesity is accompanied by several metabolic changes including insulin resistance, hyperinsulinemia, dyslipidemia, hyperleptinemia, and hepatic steatosis among others, known as the metabolic syndrome (3, 4). Thus, the search for therapies to prevent the development of metabolic syndrome has increased over the last few years, including pharmacological and dietary therapies (5-11).Previous studies have shown that long term consumption of soy protein diet reduces hyperinsulinemia, which in turn decreases the expression of the sterol regulatory element-binding protein (SREBP) 2 -1c in liver, reducing hepatic steatosis (12). Furthermore, recent evidence showed that soy protein is able to reduce hepatic lipotoxicity even in the presence of hyperinsulinemia and hyperleptinemia by a reduction in the expression of lipogenic genes and an increase in oxidative pathways (13). This evidence suggests that the type of dietary protein may play an important role in preventing the development of the metabolic syndrome.It is not clear whether the effect of consumption of soy protein on serum insulin concentration is associated with changes in...

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“…A number of studies have demonstrated that L-arginine triggers insulin release in the presence of D-glucose (1)(2)(3)(4). The underlying mechanisms are not fully elucidated.…”

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confidence: 99%

l-Arginine: An Ultradian-Regulated Substrate Coupled With Insulin Oscillations in Healthy Volunteers

Schaefer¹,

Simon²,

Viola³

et al. 2003

Diabetes Care

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OBJECTIVE -Coupled oscillations of 50 -110 min in insulin and glucose have been found previously in healthy men under continuous enteral nutrition. Because L-arginine induces insulin release as glucose does, we tested the hypothesis that L-arginine can also display such an ultradian rhythm.RESEARCH DESIGN AND METHODS -Seven healthy male subjects participated in one experimental night during which blood was sampled every 10 min from 2300 to 0700. Plasma glucose, C-peptide, and L-arginine levels were measured simultaneously. The insulin secretion rate (ISR) was calculated from plasma C-peptide levels by a deconvolution procedure. RESULTS -Plasma glucose followed the recognizable profiles, with oscillations closely linked to similar changes in the ISR. Pulse analysis of L-arginine profiles revealed significant oscillations linked to glucose and ISR oscillations, with the highest cross-correlation coefficients at time lag 0 ranging from 0.380 to 0.680 for glucose and L-arginine and from 0.444 to 0.726 for ISR and L-arginine (P Ͻ 0.01). The mean period of L-arginine oscillations was 77.2 Ϯ 6.2 min, and their mean amplitude was 19.9 Ϯ 1.7%, similar to that of glucose (17.0 Ϯ 1.9%), when expressed as the percentage of mean overnight levels.CONCLUSIONS -This newly discovered ultradian rhythm of L-arginine and its coupling with glucose and ISR oscillations sheds new light on the regulation of L-arginine, the substrate of numerous metabolic pathways, including nitric oxide synthesis. These oscillations may be of significance in conditions of hyperinsulinemia or abnormal glucose tolerance. Diabetes Care 26:168 -171, 2003A number of studies have demonstrated that L-arginine triggers insulin release in the presence of D-glucose (1-4). The underlying mechanisms are not fully elucidated. The insulinotropic action of L-arginine has been ascribed to transporter-mediated accumulation of this cationic amino acid inside the ␤-cells, with resulting depolarization of the plasma membrane (2,3). One other putative mechanism is the formation of nitric oxide (NO) from Larginine by the action of NO synthase in pancreatic ␤-cells (4 -7). It has been reported that systemic infusion of Larginine induces vasodilation, inhibits platelet aggregation, and reduces blood viscosity and that these effects are mediated by NO release (8,9). Although there might be a dietary need for L-arginine, it is produced endogenously from the turnover of the urea cycle within the liver and via conversion of citrulline to arginine in the renal proximal tubule (10,11).In normal humans, the insulin secretion rate (ISR) presents an oscillatory pattern characterized by slow ultradian oscillations with a period of 50 -110 min coexisting with rapid small fluctuations of 8 -15 min. These ISR oscillations are closely associated with similar oscillations in plasma glucose and are best seen in situations of insulin stimulation, such as during continuous enteral nutrition (12), after meal ingestion (13), and during intravenous glucose infusion (14). Abnormalities in their pa...

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Stimulus-secretion coupling of arginine-induced insulin release. Functional response of islets to l-arginine and l-ornithine

Cited by 66 publications

References 20 publications

Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids

Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids

Pancreatic Insulin Secretion in Rats Fed a Soy Protein High Fat Diet Depends on the Interaction between the Amino Acid Pattern and Isoflavones

l-Arginine: An Ultradian-Regulated Substrate Coupled With Insulin Oscillations in Healthy Volunteers

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