Amino acids as in vitro secretogogues of avian pancreatic polypeptide (APP) and insulin from the chicken pancreas (original) (raw)
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Insulin-secretional effect of exogenic amino acids in rabbits
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 1993
D,L-arginine and L-lysine, introduced into the alimentary canal (IAC), caused significant secretion of insulin in rabbits, whereas D,L-methionine or L-phenylalanine evoked only a small effect. Also, intravenous (IV) injection of D,L-arginine caused dose dependent and biphasic insulin output. On the other hand, L-phenylalanine given IV decreased both basal and glucose--stimulated insulin level in blood.
Insulin regulation of amino acid transport in mesenchymal cells from avian and mammalian tissues
Biochemical Journal, 1976
Insulin regulation of amino acid transport across the cell membrane was studied in a variety of mesenchymal cell directly isolated from avian and mammalian tissues or collected from confluent cultures. Transport activity of the principal systems of mediation in the presence and absence of insulin was evaluated by measuring the uptake of representative amino acids under conditions approaching initial entry rates. Insulin enhanced the transport rate of substrate amino acids from the A system(α-aminoisobutyric acid, L-proline, glycine, L-alanine and L-serine) in fibroblasts and osteoblasts from chick-embryo tissues, in mesenchymal cells (fibroblasts and smooth muscle cells) from immature rat uterus, in thymic lymphocytes from young rats and in chick-embryo fibroblasts from confluent secondary cultures. In these tissues, the uptake of amino acid substrates of transport systems L and Ly+ (L-leucine, L-phenylalanine, L-lysine) was not affected by the presence of the hormone. No insulin co...
In vitro stimulation of insulin release by non-metabolizable, transport-specific amino acids
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1971
The insulin-releasing ability and uptake characteristics of non-metabolizable, transport-specific amino acids were studied in an in vitro system, using microdissected pancreatic islets with more than 9 ° O//o/~-cells. Among the four stereoisomers of 2-aminobicyclo(2,2,i)heptane-2-carboxylic acid (BCH), only the b(-) form stimulated insulin release. This isomer is known as a specific substrate for transport system L in other cells. It was rapidly taken up by the islet cells and stimulated insulin release both in the presence and in the absence of glucose. 4-Amino-I-guanylpiperidine-4-carboxylic acid (GPA), a substrate for cationic transport systems, stimulated insulin release in the presence but not in the absence of glucose. In this respect GPA is similar to arginine. Like arginine, GPA also accumulated in the islet cells to yield distribution ratios well above unity. The results are consonant with the previous hypothesis that amino acids stimulate insulin release by binding to specific transport molecules. Abbreviations: BCH, 2-aminobicyclo(2,2,I)heptane-2-carboxylic acid; GPA, 4-aminoi-guanylpiperidine-4-carboxylic acid.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1972
The transport of L-leucine and D-leucine was studied in microdissected pancreatic islets of obese-hyperglycemic mice. These islets consist to more than 9 ° % of r-cells and are known to release insulin in response to L-leucine but not in response to D-leucine. Both L-leucine and D-leucine were distributed in a space that was larger than that occupied by sucrose, suggesting that both leucine isomers penetrated into the r-cells. The uptake of either isomer was inhibited by L-isoleucine, L-tryptophan, t-phenylalanine and glycine. L-Leucine inhibited the uptake of D-leucine, and D-leucine inhibited the uptake of L-leucine. There was no detectable difference between L-leucine and D-leucine with respect to the concentration dependence of uptake as measured in relation to sucrose. A significantly greater uptake of L-leucine than of D-leucine may be due to the fact that L-leucine was incorporated into islet protein. It appears that D-leucine and L-leucine are largely transported by the same system in pancreatic fl-cells. Consequently, it may be necessary to somewhat qualify the current hypothesis suggesting that the site signalling insulin release in response to L-leucine is identical with the receptor site of transport system L. Abbreviations: BCH, 2-amino-bicyelo(2,2,l)heptane-2-carboxylic acid; GPA, 4-amino-I-guanylpiperidine-4-carboxylic acid.
Metabolism-clinical and Experimental, 1982
In the absence of another exogenous nutrient, L-glutamine does not stimulate insulin release from rat pancreatic islets or isolated perfused pancreases. L-glutamine. however. augments insulin release evoked by L-leucine. These two amino acids could interact by providing both the substrate (L-glutamate) and an activator IL-leucine) for the reaction catalyzed by glutamate dehydrogenase. Under suitable experimental conditions, as little as 0.5 mM L-glutamine is sufficient to enhance leucine-stimulated insulin release. When the pancreases or islets are first exposed to L-glutamine and then stimulated with L-leucine, the rate of secretion is much higher than that evoked by L-leucine in tissue not first exposed to L-glutamine. The memory of a prior exposure to L-glutamine persists for at least 25 min after removal of the latter amino acid from the extracellular fluid. This memory phenomenon is not dependent on the presence of Ca*+ in the extracellular fluid during the first exposure to L-glutamine, but is suppressed when such a prior exposure is performed in the absence of extracellular Kf. The memory phenomenon could be due, in part at least, to inhibition by L-glutamine of K' conductance in the B-cell plasma membrane. Moreover, the amount of L-glutamate which accumulates in islets exposed to L-glutamine is sufficient to maintain, for a much longer period than with other nutrient secretagogues, a sustained increase in catabolic fluxes after removal of the amino acid from the extracellular fluid.
General and Comparative Endocrinology, 1978
Isolated chicken and rat adipocytes and hepatocytes were used to compare chicken vs mammalian pancreatic hormones in regulating glucose and lipid metabolism. Porcine glucagon is twice as potent as chicken glucagon in eliciting lipolysis in both rat and chicken adipocytes. A less marked but significant difference exists between the two glucagon homologs when glucose release by isolated hepatocytes is measured. Chicken adipocytes respond to lower concentrations (1 rig/ml) of glucagon than rat adipocytes (5 r&ml). Hepatocytes from both animal species responded to glucagon at concentrations of 1 @ml. Chicken insulin is slightly more potent than porcine insulin both in inducing glucose utilization and in inhibiting glucagon-stimulated lipolysis in rat adipocytes. Glucose utilization, basal lipolysis, and the rate of glucagon-stimulated lipolysis of the chicken adipocyte are unaltered by insulin concentrations which are 1000 times greater than those required to affect rat adipocytes. The antilipolytic action of avian pancreatic polypeptide (APP) was compared with the bovine homolog of APP, namely bovine pancreatic polypeptide
Amino acid metabolism, insulin secretion and diabetes
Biochemical Society Transactions, 2007
In addition to the primary stimulus of glucose, specific amino acids may acutely and chronically regulate insulin secretion from pancreatic β-cells in vivo and in vitro. Mitochondrial metabolism is crucial for the coupling of glucose, alanine, glutamine and glutamate recognition with exocytosis of insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP (the main coupling messenger in insulin secretion) and other factors that serve as sensors for the control of the exocytotic process. The main factors that mediate the key amplifying pathway over the Ca 2+ signal in nutrient-stimulated insulin secretion are nucleotides (ATP, GTP, cAMP and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and glutamate. In addition, after chronic exposure, specific amino acids may influence gene expression in the β-cell, which have an impact on insulin secretion and cellular integrity. Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion.
Archives of Biochemistry and Biophysics, 1984
I. The metabolic situation found in pancreatic islets exposed to both L-glutamine and 2-ketoisocaproate was investigated in order to assess its relevance to the synergistic effects of these nutrients upon insulin release. 2. In islet homogenates, several 2-keto acids could be used as partners for the transamination of L-glutamate to 2-ketoglutarate. The rate of transamination did not correlate positively with the capacity of each 2-keto acid to stimulate insulin release in the presence of L-glutamine. 3. L-Glutamine enhanced the production of L-leucine from 2-ketoisocaproate and inhibited the conversion of the 2-keto acid to acetoacetate and CO2. L-Glutamine also inhibited the oxidation of pyruvate. 4. In the presence of 2-ketoisocaproate, the rate of generation of 2-ketoglutarate from exogenous L-glutamine was increased, but the oxidative deamination of glutamate was suppressed. 5. L-Valine antagonized the effect of 2-ketoisoeaproate to augment 14C02 output from islets prelabelled with L-[U-~4C]glutamine. 6. L-Glutamine did not increase the islet content of reduced pyridine nudeotides beyond the high level reached in the sole presence of 2-ketoisocaproate. 7. If allowance was made for the influence of exogenous nutrients upon the oxidation of endogenous nutrients, the insulin output evoked by L-glutamine and/or 2-keto acids tightly depended on the increment in oxidation rate attributable to these nutrients. 8. The metabolic and secretory responses to L-glutamine and 2-ketoisoeaproate were best explained by a stimulation of transamination reactions between 2-ketoisocaproate and glutamate derived from exogenous glutamine. * This paper is the sixth in a series. Materials and Methods All experiments were performed with islets removed from fed albino rats. For the measurement of transaminase activity, groups of 400 islets each were sonicated (2 X 5 s) in 0.7 ml of a Tris-acetate buffer (10 mM, pH 8.6). The reaction mixture (100 #1) contained (final concentrations) 50 mM Tris-acetate (.pH 8.6), 2 mM L-[U-14C]-.glutamate, 50/.tM, pyridoxal phosphate, 1.4 mM mercaptoethanol, 10 mM of an unlabeUed 2-keto acid and 30 ~1 islet homogenate. After 20 rain incubation at 30°C, the reaction was stopped by diluting the reaction mixture 15-fold with cold H20 (0-4°C)and immediately passing it through an ion-exchange resin