Insulin-secretional effect of exogenic amino acids in rabbits (original) (raw)
Diabetologia, 2006
Aims/hypothesis The aim of our study was to establish whether the well-known defective or absent secretion of glucagon in type 1 diabetes in response to hypoglycaemia is selective or includes lack of responses to other stimuli, such as amino acids. Materials and methods Responses of glucagon to hypoglycaemia were measured in eight patients with type 1 diabetes and six non-diabetic subjects during hyperinsulinaemic (insulin infusion 0.5 mU kg −1 min −1) and eu-, hypo-and hyperglycaemic clamp studies (sequential steps of plasma glucose 5.0, 2.9, 5.0, 10 mmol/l). Subjects were studied on three randomised occasions with infusion of low-or high-dose alanine, or saline. Results With saline, glucagon increased in hypoglycaemia in non-diabetic subjects but not in diabetic subjects. Glucagon increased further with low-dose (181±16 ng l −1 min −1) and high-dose alanine (238±20 ng l −1 min −1) in non-diabetic subjects, but only with high-dose alanine in diabetic subjects (area under curve 112±5 ng l −1 min −1). The alanine-induced glucagon increase in diabetic subjects paralleled the spontaneous glucagon response to hypoglycaemia in non-diabetic subjects not receiving alanine. The greater responses of glucagon to hypoglycaemia with alanine infusion were offset by recovery of eu-or hyperglycaemia. Conclusions/interpretation In type 1 diabetes, the usually deficient responses of glucagon to hypoglycaemia may improve after increasing the concentration of plasma amino acids. Amino acid-enhanced secretion of glucagon in response to hypoglycaemia remains under physiological control since it is regulated primarily by the ambient plasma glucose concentration. These findings might be relevant to improving counter-regulatory defences against insulininduced hypoglycaemia in type 1 diabetes.
General and Comparative Endocrinology, 1982
The potential for a direct effect of selective amino acids on avian pancreatic polypeptide (APP) and insulin secretion was investigated using a system of perifused microfragments of chicken pancreas. Leucine, isoleucine, phenylalanine, and valine produced a sustained increase in APP release when each was evaluated at 5-mM concentrations; 15 mM arginine also produced a sustained increase in APP secretion. The secretory response differed among the amino acids such that 5 mir4 leucine and isoleucine produced a transitory increase in insulin secretion while lysine, phenylalanine, and arginine produced a sustained increase in insulin secretion. In general, APP secretion exhibited a greater maximal response and a lower threshold for stimulation by various amino acids in vitro than did insulin. The significance of this effect is somewhat unclear due to the failure of intravenous arginine or leucine to alter circulating levels of APP in vivo. In conclusion, amino acids directly increase APP secretion from the chicken pancreas in vitro; although they are relatively unresponsive to glucose, perifused chicken B cells respond to amino acids as do B cells from mammalian species.
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.
Amino acid metabolism, β-cell function, and diabetes
2006
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):
Journal of Diabetes and its Complications, 2007
Aim: The acute effects of the oral administration of l-alanine (l-ala), l-glutamine (l-gln), l-ala+l-gln, and l-alanyl-l-glutamine (AGP) on glycemia recovery during short-term insulin-induced hypoglycemia (IIH) were compared. Methods: For this purpose, the blood glucose levels of 24-h-fasted rats that received intraperitoneal injections of regular insulin (IIH group) or saline [control (COG) group] and, 15 min later, oral administration of l-ala (100 mg/kg), l-gln (100 mg/kg), l-ala (50 mg/kg)+l-gln (50 mg/kg), or AGP (100 mg/kg) were compared. Liver perfusion experiments and blood collection to measure blood glucose levels were performed 30 min after insulin (1.0 U/kg) or saline injection. Livers from the IIH and COG groups were perfused with saturating concentrations of l-ala, l-gln, l-ala+l-gln, or AGP, and the maximal hepatic production of glucose, urea, ammonia, l-lactate, and pyruvate was evaluated. Results: In contrast with l-gln, l-ala+l-gln, or AGP, the oral administration of l-ala promoted glycemia recovery. In agreement with these results, livers from IIH rats showed maximal hepatic production of glucose and urea from l-ala with 50% of the amount used to obtain the maximal hepatic production of glucose and urea in livers from COG rats. In contrast with l-gln, l-ala+l-gln, or AGP, the maximal hepatic production of urea from l-ala occurred in the absence of ammonia accumulation. Conclusion: The results indicate that the best glycemia recovery promoted by the oral administration of l-ala was a consequence of the higher efficiency of the livers from IIH rats in producing glucose from l-ala. D
Amino Acid Metabolism, -Cell Function, and Diabetes
Diabetes, 2006
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):
Evaluation of Pancreatic and Extra Pancreatic Effects of Branched Amino Acids
Romanian Journal of Diabetes Nutrition and Metabolic Diseases, 2019
Background and aims: Leucine, Isoleucine, and Valine collectively known as Branchedchain amino acids (BCAAs), can be closely associated with metabolic dysregulates and with insulin resistance. We aimed to explore the role of BCAAs as potential treatment option for diabetes. Material and method: Bioassay the effect of BCAAs on MIN6 cell line on insulin secretion and pancreatic beta cells expansion, then were checked for inhibitory potential of pancreatic amylase, glucosidase and lipase as alternative approach for diabetes treatment. Results: BCAAs significantly enhance insulin secretion parallel to L-alanine efficacy. Furthermore, BCAAs obtain a dose dependent β-cell proliferation similar to glucagon-like peptide-1. Moreover, these acids could restore the secretory function of MIN6 β-cell despite stressful gluco-lipo-toxicity; separately or combined. Moreover, BCAAs exerted a dose dependent dual inhibition of amylase, glucosidase and lipase. Conclusions: Our current findings suggest that BCAAs supplementation may have a potential therapeutic effect against diabetes as insulin releasing agent and as specific inhibitors for both-amylase/α-amyloglucoside and lipase
BMC Biochemistry, 2011
Background: The generation of energy from glucose is impaired in diabetes and can be compensated by other substrates like fatty acids (Randle cycle). Little information is available on amino acids (AA) as alternative energysource in diabetes. To study the interaction between insulin-stimulated glucose and AA utilization in normal and diabetic subjects, intraportal hyperinsulinaemic euglycaemic euaminoacidaemic clamp studies were performed in normal (n = 8) and streptozotocin (120 mg/kg) induced diabetic (n = 7) pigs of~40-45 kg.
Amino acids and diabetes: implications for endocrine, metabolic and immune function
Frontiers in Bioscience, 2011
2. Structure and hormones of the pancreatic islets 3. Glucose stimulated insulin secretion from the beta cell 4. Mechanisms underlying beta cell actions of amino acids 4.1. Alanine 4.2. Arginine 4.3. Cysteine 4.4. Glutamine 4.5. Glutamate 4.6. Homocysteine 4.7. Leucine 4.8. Taurine 5. Mechanisms underlying alpha cell actions of amino acids 6. Amino acids and muscle function in diabetes 7. Amino acids and liver function in diabetes 8. Amino acids and endothelial cell function in diabetes 9. Amino acids and immune function in diabetes 9.1. Neutrophils 9.2. Lymphocytes 10. Concluding remarks 11. Acknowledgements 12. References
Nutrients, 2020
Different amino acids (AAs) may exert distinct effects on postprandial glucose and insulin concentrations. A quantitative comparison of the effects of AAs on glucose and insulin kinetics in humans is currently lacking. PubMed was queried to identify intervention studies reporting glucose and insulin concentrations after acute ingestion and/or intravenous infusion of AAs in healthy adults and those living with obesity and/or type 2 diabetes (T2DM). The systematic literature search identified 55 studies that examined the effects of l-leucine, l-isoleucine, l-alanine, l-glutamine, l-arginine, l-lysine, glycine, l-proline, l-phenylalanine, l-glutamate, branched-chain AAs (i.e., l-leucine, l-isoleucine, and l-valine), and multiple individual l-AAs on glucose and insulin concentrations. Oral ingestion of most individual AAs induced an insulin response, but did not alter glucose concentrations in healthy participants. Specific AAs (i.e., leucine and isoleucine) co-ingested with glucose exe...