Amino Acid Infusion Research Articles

The Impact of Amino Acids on Postprandial Glucose and Insulin Kinetics in Humans: A Quantitative Overview.

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 exerted a synergistic effect on the postprandial insulin response and attenuated the glucose response compared to glucose intake alone in healthy participants. Oral AA ingestion as well as intravenous AA infusion was able to stimulate an insulin response and decrease glucose concentrations in T2DM and obese individuals. The extracted information is publicly available and can serve multiple purposes such as computational modeling.

Acute hyperaminoacidemia does not suppress insulin-mediated glucose turnover in healthy young men.

Elevated circulating amino acids (AA) concentrations are purported to cause insulin resistance (IR) in humans. To quantify hyperaminoacidemia effects on insulin-mediated glucose turnover in healthy men, we performed 2-stage pancreatic clamps using octreotide with glucagon and growth hormone replacement. In the basal stage, insulin was infused to maintain euglycemia at postabsorptive levels. During the clamp stage, insulin was raised to postprandial levels, glycemia clamped at 5.5 mmol/L by glucose infusion, and branched-chain AA (BCAA) maintained at either postabsorptive (Hyper1; n= 8) or postprandial (Hyper2; n= 7) by AA infusion. Glucose turnover was measured by d-3-[3H]glucose dilution. Octreotide suppressed C-peptide; glucagon, growth hormone, and glycemia were maintained at postabsorptive levels throughout. Insulin did not differ at postabsorptive (72 ± 5 vs. 60 ± 5 pmol/L; Hyper1 vs. Hyper2) and increased to similar concentrations at basal (108 ± 11 vs. 106 ± 14) and clamp stages (551 ± 23 vs. 540 ± 25). Postabsorptive BCAA were maintained during Hyper1 and increased >2-fold (830 ± 26 µmol/L) during Hyper2. Endogenous glucose production was similarly suppressed (0.95 ± 0.16 vs. 1.37 ± 0.23mg/kg lean body mass/min; Hyper1 vs. Hyper2) and basal glucose disposal (3.44 ± 0.12 vs. 3.67 ± 0.14) increased to similar levels (10.89 ± 0.56 vs. 11.11 ± 1.00) during the clamp. Thus, acute physiological elevation of AA for 3 h did not cause IR in healthy men. Novelty: A 2-step pancreatic clamp was used to quantify the effect of AA on insulin sensitivity in humans. Acute physiological elevation of circulating AA to postprandial levels does not cause IR in healthy men.

Renal functional reserve: from physiological phenomenon to clinical biomarker and beyond.

Glomerular filtration rate (GFR) is acutely increased following a high-protein meal or systemic infusion of amino acids. The mechanisms underlying this renal functional response remain to be fully elucidated. Nevertheless, they appear to culminate in preglomerular vasodilation. Inhibition of the tubuloglomerular feedback signal appears critical. However, nitric oxide, vasodilator prostaglandins, and glucagon also appear important. The increase in GFR during amino acid infusion reveals a "renal reserve," which can be utilized when the physiological demand for single nephron GFR increases. This has led to the concept that in subclinical renal disease, before basal GFR begins to reduce, renal functional reserve can be recruited in a manner that preserves renal function. The extension of this concept is that once a decline in basal GFR can be detected, renal disease is already well progressed. This concept likely applies both in the contexts of chronic kidney disease and acute kidney injury. Critically, its corollary is that deficits in renal functional reserve have the potential to provide early detection of renal dysfunction before basal GFR is reduced. There is growing evidence that the renal response to infusion of amino acids can be used to identify patients at risk of developing either chronic kidney disease or acute kidney injury and as a treatment target for acute kidney injury. However, large multicenter clinical trials are required to test these propositions. A renewed effort to understand the renal physiology underlying the response to amino acid infusion is also warranted.

Green coffee derived supplements and infusions as a source of polyamines and free amino acids

This work reports on monoamines (MA), diamines (DA) and polyamines (PA) as well as free amino acids (fAA) in nutritional supplements and infusions derived from green coffee beans. Samples were investigated using a ultra-high performance liquid chromatography UV/FLR method, which was validated regarding specificity, linearity, range, precision, accuracy and limits of detection and quantification. Nutritional supplements based on green coffee beans showed large amounts of total amines ranging from 1090 to 2593 mg/kg, with exceptional high levels of spermidine up to 724 mg/kg, and a content of fAA from 4004 to 12,389 mg/kg. Infusions brewed from green coffee beans showed much lower contents of amines (14–17 mg/L) and fAA (78–100 mg/L). However, if the customary edible portion was considered, infusions from green coffee were a mainly better source for MA and PA as well for fAA, compared to nutritional supplements. Tryptamine and tyramine were predominant as MA putrescine as DA, and spermidine as PA, respectively.Graphic abstract

Comparative Evaluation of Therapeutic Modules for Treatment of Parvoviral Gastroenteritis in Dogs

The present study was conducted on 18 clinically affected dogs of different breeds and age. All the dogs were divided into three groups A, B and C consisting of 6 animals in each one. Group A dogs were given standard therapy. In group B dogs were treated with immune plasma besides standard therapy. In group C dogs were treated with amino acid infusion besides standard therapy. In group A 3 out of 6 dogs (50%) showed complete recovery from dehydration and other clinical signs on day 4 post-treatments, while remaining 3 dogs (50%) recovered on day 5 post-treatments. In group B 4 dogs (66.66%) recovered completely from dehydration and other clinical signs on day 3 post-treatment, while remaining dogs (33.33%) recovered on day 4 post-treatment. In group C 5 dogs (83.33%) recovered completely from dehydration and other clinical sign on day 2 post-treatment, while remaining dogs (16.66%) recovered on day 3 post-treatment. It has been concluded that among various treatment groups, group C (Amino acid + Supportive therapy) was found to be superior as all six (6) dogs recovered day 3 post-treatment.

Evaluation of the incidence of acute nausea and vomiting after administration of an amino acid solution containing only arginine and lysine with lutetium Lu-177 dotatate.

12113 Background: Lutetium Lu-177 dotatate is used to treat patients with gastroenteropancreatic neuroendocrine tumors, and an amino acid (AA) solution must be administered concurrently to mitigate nephrotoxicity. AA solutions may lead to increased rates of nausea and vomiting (NV) due to the inclusion of unnecessary non-essential and essential AA. Methods: This study is a single academic center retrospective chart review from October 6th, 2015 to December 17th, 2019 evaluating the incidence of acute NV in adult patients after administration of an AA solution containing only arginine 25 grams and lysine 25 grams in 1 liter of normal saline (Arginine-Lysine amino acid [AL AA]) with lutetium Lu-177 dotatate. The incidence of acute NV will be compared to the historical incidence in patients administered Parenteral amino acids 10%, Aminosyn II 10% or Clinisol 15% (commercial AA). Secondary endpoints include the incidence of rescue anti-emetic usage and the percentage of patients that require interruption of the AA infusion. Acute NV are defined as any occurrence of NV within twenty-four hours of the AA infusion. Results: 53 patients received a total of 164 treatments with the AL AA, while 18 patients received a total of 48 treatments with the commercial AA. The AL AA significantly decreased the incidence of acute NV, the mean AA infusion time, the interruption of the AA infusion, and the utilization of rescue anti-emetics compared to the commercial AA (Table) in patients on lutetium Lu-177 dotatate. Conclusions: The study findings support the use of an AL AA to be administered concurrently with lutetium Lu-177 dotatate to minimize commercial AA related acute NV. [Table: see text]

SAT-LB311 Inoperable, Metastatic Pheochromocytoma & Paraganglioma Tumor Size Reduction After Lu-177-dotatate (Lutathera®) Treatment Trial: The Role of Nursing

Tumor Size Reduction after Lu-177-DOTATATE (Lutathera®) Treatment in Patients with Inoperable Metastatic Pheochromocytoma and Paraganglioma: The Role of NursingAssumpta Ude, Frank I. Lin, Karel Pacak, Ejigayehu Demissie. Clinical Center Nursing Department, Molecular Imaging Program NCI, Endocrine Service Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development. Background: Nursing management of patients with metastatic pheochromocytoma (PCC) and paraganglioma (PGL) undergoing treatment trial with radiopharmaceutical medication has unpredictable clinical outcomes. Clinical Case: A 52-year old woman with inoperable metastatic PCC/PGL was admitted into protocol 17-C-0087 after poor response to various chemotherapies. Patient was treated in the endocrine nursing unit with 200 mCi of Lu-177-DOTATATE (Lutathera®) intravenous infusion given by a radionuclide specialist every eight weeks for a total of four doses. Prior to admission, various members of the endocrine clinical nursing leadership team reviewed protocol with the medical and radiation safety team and a clinical research nurse (CRN) to ensure CRNs understand their roles and expectations to ensure patient safety during procedures and treatment. The patient was admitted on the day preceding the treatment and monitored for 48 hours afterwards. The CRN obtained comprehensive diet and medication history to determine if there is anything that may falsely elevate plasma/urinary catecholamines/metanephrines. The CRN ensured correct placement of intravenous (IV) line and proper collection of blood from IV line to increase the reliability of results. The CRN ensured that IV amino acid (Clinisol 15 %) infusion was administered 30 minutes prior to dosing to diminish renal issues. This patient had minimal side effects and no adverse events to therapy. The research team followed up the patient in clinic every month while she was on treatment, then every 3 months in the follow-up period. Recent evaluation showed this patient had stable vital signs, impalpable supraclavicular lymph node, returned to baseline physical activity with significant decrease in the size of the PCC/PGL, and reduction in serum catecholamine/metanephrine levels. Conclusion: The endocrine CRN team is critical in the assessment, monitoring, observation and education of patients and families regarding expectations during therapy which played a significant role in minimizing the patient’s side effects to therapy. Working collaboratively with other members of the multidisciplinary research team also contributed to patient’s favorable outcome.

Do Nutritional Interventions Improve the Outcomes of Patients with Cirrhosis and Ascites: A Systematic Review of Randomized Trials.

Ascites is a common, morbid complication of cirrhosis. Nutritional interventions such as sodium-restriction and high-protein diet are considered standard of care. However, their evidence base is limited. We performed a systematic review of randomized trials of nutritional interventions for ascites. Increasing consumption of calories and protein alone was ineffective. Studies reached contradictory conclusions regarding sodium restriction in patients taking combination diuretics. Intravenous amino acid infusion alone did not improve outcomes, peripheral parenteral nutrition did not improve outcomes except alone but reduced mortality in conjunction with branched-chain amino acid evening snack. Patients may benefit from sodium restriction and a protein-rich evening snack. Future trials should prioritize standardizing nutritional targets and tailoring interventions to the specific needs of patients including the socioeconomic factors impacting adherence.

Effect of peptide receptor radionuclide therapy (PRRT) with tandem isotopes - [90Y]Y/[177Lu]Lu-DOTATATE in patients with disseminated neuroendocrine tumours depending on [18F]FDG PET/CT qualification in Polish multicentre experience - do we need [18F]FDG PET/CT for qualification to PRRT?

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). The aim of the study was the evaluation of the role of [¹⁸F]FDG PET/CT in predicting response, progression-free survival (PFS) and overall survival (OS) after tandem therapy [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE. Seventy-five patients with histopathologically proven NET G1 and G2 were included in the study. Before treatment [⁶⁸Ga]Ga-DOTATATE PET/CT and [¹⁸F]FDG PET/CT was performed. Patients were treated with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE (1:1) with mixed amino-acid infusion for kidney protection. Progression-free survival was 22.2 months for [¹⁸F]FDG-positive patients and 59.3 months for [¹⁸F]FDG-negative patients (p = 0.003). The OS from diagnosis (OS-D) and from the start of PRRT (OS-T) was not reached in [¹⁸F]FDG-negative patients, and in [¹⁸F]FDG-positive patients it was 71.8 months and 55.8 months, respectively. The observed overall one-year survival in [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients was 96.8% vs. 99.1%, two-year survival was 88.9% vs. 96%, and five-year survival was 58.8% vs. 88%, respectively. The one-year and two-year risk of progression was 15%vs. 58.9% in [¹⁸F]FDG-positive patients and 11% vs. 32% in [18F]FDG-negative patients. The objective response rate (ORR) [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients was 41.7% vs. 17%. [¹⁸F]FDG-positive patients have statistically significant shorter survival parameters than [¹⁸F]FDG-negative patients. The risk of progression in [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients in one-year follow-up is comparable, whereas in two-year follow-up it is nearly two times higher for [¹⁸F]FDG PET/CT-positive patients.

Successful Long-Term Management of Canine Superficial Necrolytic Dermatitis With Amino Acid Infusions and Nutritionally Balanced Home-Made Diet Modification

A 10-year old, castrated male, Bichon Frise with a history of hyperadrenocorticism and intrahepatic portal vein hypoplasia was diagnosed with superficial necrolytic dermatitis (SND). The dog exhibited thick crusts on the chin, muzzle, prepuce, and paws. In addition, the dorsal surfaces of all paws were erythematous while the palmar/plantar surfaces were hyperkeratotic, hardened, and painful. The dog was treated with intravenous amino acid infusions (AAI), raw egg yolks, as well as zinc and omega-3 fatty acid oral supplements. The dog required AAI once every 2–3 weeks because this coincided with recrudescence of painful skin lesions. The dog was subsequently diagnosed with diabetes mellitus. A consult with the Nutrition Service was pursued 220 days after the original SND diagnosis because of concern for feeding raw eggs and for malnutrition since appetite was variable, muscle condition was reduced, and greater than 50% of ingested calories were from foods that were not nutritionally complete. There was also concern regarding the variability of the diet and the impact it would have on the management of diabetes mellitus. The diet was prepared by the dog owner according to a provided recipe and presented twice daily. The diet was rich in high quality protein and fat. All other treatments including medications, supplements, and bathing schedule remained unchanged at the time of diet modification. The dog was subclinical for SND associated clinical signs approximately 3 weeks after the diet modification, which also coincided with the last AAI. The AAI was postponed and was next administered 7 weeks later (i.e., 10 weeks from the previous infusion). The dog remained subclinical for SND related clinical signs and continued to receive AAI once every 10–12 weeks until he was euthanized 718 days later for complications related to severe multi-drug resistant, skin infections. In conclusion, this report highlights a novel role for nutritionally balanced home-made diets designed by a board-certified veterinary nutritionist could substantially increase time interval between AAI and outcome in dogs with SND.

Outcomes of lactulose plus branched-chain amino acid infusion and lactulose alone for hepatic encephalopathy: A retrospective cohort study using a national inpatient database.

Previous randomized controlled trials of branched-chain amino acid infusion for hepatic encephalopathy involved a small number of patients, and the effectiveness of branched-chain amino acid infusion has not been clarified. We evaluated whether branched-chain amino acid infusion in addition to lactulose treatment was associated with short-term outcomes in a large population of patients. Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients with hepatic encephalopathy who received lactulose within 2days of admission from July 2011 to March 2017. We divided the patients into those who received branched-chain amino acid infusion within 2days of admission in addition to lactulose treatment and those who did not. We conducted propensity-score inverse probability of treatment weighting analyses to compare in-hospital mortality, consciousness at discharge, in-hospital complications, length of stay, and total hospitalization costs between the groups. We identified 8051 patients with hepatic encephalopathy treated with lactulose, including 7560 patients who received lactulose plus branched-chain amino acid infusion and 491 who received lactulose alone. The lactulose plus branched-chain amino acid infusion group had a significantly lower mortality than the lactulose alone group (9.6% vs. 15.0%, odds ratio 0.60, 95% confidence interval 0.44-0.82). The lactulose plus branched-chain amino acid infusion group also had a lower proportion of patients with impaired mental status at discharge, and lower total hospitalization costs than the lactulose alone group. Branched-chain amino acid infusion together with lactulose may improve the prognosis of hepatic encephalopathy.

Tandem peptide receptor radionuclide therapy using 90Y/177Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience

IntroductionOne of the concepts of theranostics in nuclear medicine is peptide receptor radionuclide therapy (PRRT), whereby labeled somatostatin analogs are used for imaging and treating inoperable or disseminated neuroendocrine tumors (NET).AimThe aim of the study was to determine the therapeutic efficacy and toxicity of tandem 90Y /177Lu-DOTATATE in patients with disseminated NET in a multicenter trial.Materials and methods103 patients with NET G1/G2 treated with 90Y/177Lu-DOTATATE (1:1) with amino-acid infusion for nephroprotection were included in the study.ResultsOverall survival from the disease diagnosis (OS-D) was 127.4 months and from the time of PRRT (OS-T) was 89.5 months. Progression-free survival (PFS) was 29.9 months. An analysis based on the proliferation index revealed a statistically significant impact on PFS and OS-T (PFS G1 vs G2, 59.3 vs 24.3 months; OS-T G1 vs G2, not reached vs 79.9 months). The effect of the primary disease site was also analyzed. For pancreatic vs small bowel vs large bowel, the PFS was 30.8 vs 30.3 vs 40.6 months, the OS-T was 94 vs 61.9 vs 131.2 months and OS-D was 130.4 vs 89.2 vs not reached months, respectively. The 2-year risk of progression was 42%. The probability of 2-year and 5-year overall survival was 89% and 62%, respectively. PRRT was well tolerated by all patients. One patient (1%) developed myelodysplastic syndrome. No other grade 3 and 4 hematological or renal toxicity was observed.ConclusionsThis multicenter trial showed that tandem 90Y/177Lu-DOTATATE is highly effective and safe therapy for patients with disseminated NET.

Postruminal infusions of amino acids or glucose affect metabolisms of splanchnic, mammary, and other peripheral tissues and drive amino acid use in dairy cows

Effects of AA and glucose infusions on efficiency of use of essential AA (EAA) were studied according to a 2 × 2 factorial using 5 multicatheterized cows in a 4 × 4 Latin square plus one cow, with 2-wk periods. The diet provided 87% of energy and 70% of metabolizable protein requirements, and the 4 treatments were abomasal infusions of (1) water, (2) an AA mixture with a casein profile (695 g/d), (3) glucose (1,454 g/d), or (4) a combination of AA and glucose infusions. Milk samples were collected on the last 6 milkings. On d 14, 6 blood samples were collected from arterial, and portal, hepatic, and mammary venous vessels. Splanchnic plasma flow was calculated by dilution of p-aminohippurate and mammary flow by the Fick principle using Phe + Tyr. The net flux of AA across tissues [splanchnic, i.e., portal-drained viscera (PDV) + liver, and mammary gland] was calculated as the efflux minus the influx across that tissue. The efficiency of EAA was calculated as the sum of exported true proteins [milk protein yield (MPY), scurf, and metabolic fecal protein] multiplied by their respective AA profile and divided by the predicted AA supply minus AA endogenous urinary loss. In addition, catabolism was estimated for each tissue: AA supply - (portal net flux + metabolic fecal protein) for the PDV; -hepatic net flux for the liver; splanchnic net flux- (-mammary net flux + scurf) for the other peripheral tissues; and -mammary net flux - milk for the mammary gland. The MIXED procedure (SAS Institute Inc., Cary, NC) was used with cow as a random effect. No AA × glucose interaction existed for most of the measured parameters. With infusions of AA and glucose, MPY increased by 17 and 14%, respectively. The decreased efficiency of EAA-N with AA infusion resulted from increased EAA-N in MPY smaller than the increased EAA-N supply and was accompanied by increased liver catabolism of His + Met + Phe (representing group 1 AA) and increased mammary and PDV catabolisms of group 2 AA-N (Ile, Leu, Lys, and Val). In contrast, the increased efficiency of EAA-N with glucose infusion, resulting from increased EAA-N in MPY with no change in EAA-N supply, was accompanied by decreased mammary catabolism of group 2 AA-N and hepatic catabolism of His + Met + Phe. No mammary catabolism of His, Met, and Phe existed in all treatments, as indicated by the mammary uptake to milk output ratio close to one for these EAA. Therefore, the mammary gland contributes significantly to variations of efficiency of group 2 AA-N through variations of AA catabolism, in response to both AA and glucose supplies, whereas additional PDV catabolism was observed with increased AA supply. Partition of AA use between tissues allows to delineate their anabolic or catabolic fate across tissues and better understand changes of efficiency of EAA in response to protein and energy supplies.

A Prospective, Randomized, Placebo-controlled Comparative Study of Amino Acid Supplementation in Lactation Insufficiency

ABSTRACT Objective Our study evaluates the clinical efficacy of intravenous (i/v) amino acids in the prevention of lactation insufficiency and improvement of neonatal weight gain. Design A prospective, randomized, open-label, placebo-controlled clinical trial is reported. Population or sample This study recruited 305 lactating mothers of age-group, 22–35 years. Methods Test group, n = 152, received i/v amino acid infusion, 500 mL, as study drug once daily for 4 days, and control group, n = 153, received normal saline as placebo, 500 mL od for 4 days. Main outcome measures We studied the efficacy and safety of i/v amino acids in the prevention of lactation insufficiency. We further evaluated the role of maternal amino acid supplementation in ameliorating physiological weight loss and overall neonatal weight gain. Results Lactation onset was reported in 86.3% of mothers in the amino acid group at day 0 as compared to 32.23% in the control group (p value < 0.001). Lactation was achieved by all the mothers in the study group by day 1 itself with two doses of i/v amino acids (p value < 0.001). An increase in neonatal weight was observed in the amino acid group, (2.900 ± 0.488, p value = 0.001) compared with the control group at 2 weeks (2.716 ± 0.484, p value = 0.001). Conclusion Maternal amino acid supplementation is proven to be both efficacious and safe in augmenting breast milk production, thereby preventing lactation insufficiency. It effectively prevented neonatal physiological weight loss at 2 weeks and promoted substantial weight gain over a period of a month after birth. How to cite this article Nagarathnamma R, Pooja Bhushan, Dutta T, Ezhil Arasan R. A Prospective, Randomized, Placebo-controlled Comparative Study of Amino Acid Supplementation in Lactation Insufficiency. J South Asian Feder Obst Gynae 2020;12(6):408–414.

The effect of early versus late lipid infusion in parenteral nutrition on the biochemical and cortical auditory evoked potential parameters in preterm neonates

BackgroundAs brain activity depends greatly on the functions provided by lipid membranes, dietary fat in early life can affect the developing nervous system. Despite the adoption of an early more aggressive parenteral nutrition approach with amino acid infusions still reluctance to the early use of intravenous lipids in neonates.AimTo compare the effect of delayed versus early introduction of intravenous lipid in preterm on the biochemical parameters and on brain development by the cortical auditory evoked potential (CAEP) latency and amplitude.MethodsThis is a comparative study included 49 neonates admitted at the ain shams university NICUs. Participants were divided into two groups: 26 in group of early lipid infusion and 23 in late lipid infusion, Demographic data, and biochemical parameters were documented during the 1st 2 weeks of life. The CAEP was performed at age of 6 months. The latency and amplitude of P1 were recorded and compared between both groups.ResultsIn the present work we found that group of early lipid infusion had reach their full oral intake earlier with shorter duration of parenteral nutrition and length of stay. They had better weight gain and significantly better glucose level control than group of late lipid infusion. There was no significant difference in the other chemical parameters between both groups expect for the higher incidence of cholestasis in the group of late lipid infusion. At 6 months of age, the group of early lipid infusion had significantly shorter latency and amplitude of P1 than the group of late lipid infusion.ConclusionEarly effective nutrition positively affect feeding tolerance and weight gain and maturation of higher brain centers brain.

Energy and nitrogen balance of dairy cattle as affected by provision of different essential amino acid profiles at the same metabolizable protein supply

Amino acid composition of metabolizable protein (MP) is important in dairy cattle diets, but effects of AA imbalances on energy and N utilization are unclear. This study determined the effect of different AA profiles within a constant supplemental MP level on whole-body energy and N partitioning in dairy cattle. Five rumen-fistulated Holstein-Friesian dairy cows (2.8 ± 0.4 lactations; 81 ± 11 d in milk; mean ± standard deviation) were randomly assigned to a 5 × 5 Latin square design in which each experimental period consisted of 5 d of continuous abomasal infusion followed by 2 d of rest. A total mixed ration consisting of 58% corn silage, 16% alfalfa hay, and 26% concentrate (dry matter basis) was formulated to meet 100 and 83% of net energy and MP requirements, respectively, and was fed at 90% of ad libitum intake by individual cow. Abomasal infusion treatments were saline (SAL) or 562 g/d of essential AA delivered in 4 profiles where individual AA content corresponded to their relative content in casein. The profiles were (1) a complete essential amino acid mixture (EAAC), (2) Ile, Leu, and Val (ILV), (3) His, Ile, Leu, Met, Phe, Trp, Val (GR1+ILV), and (4) Arg, His, Lys, Met, Phe, Thr, Trp (GR1+ALT). The experiment was conducted in climate respiration chambers to determine energy and N balance in conjunction with milk production and composition, digestibility, and plasma constituents. Compared with SAL, infusion of EAAC increased milk, protein, and lactose yield, increased energy retained as body protein, and did not affect milk N efficiency. Total N intake and urine N output was higher with all AA infusions relative to SAL. Compared with EAAC, infusions of GR1+ILV and GR1+ALT produced the same milk yield and the same yield and content of milk fat, protein, and lactose, and had similar energy and N retention. Milk N efficiency was not different between EAAC and GR1+ILV, but was lower with GR1+ALT compared with EAAC, and tended to be lower with GR1+ALT compared with GR1+ILV. Infusion of ILV tended to decrease dry matter intake compared with the other AA infusions. Milk production and composition was not different between ILV and SAL. Compared with EAAC, infusion of ILV decreased or tended to decrease milk, protein, and lactose yields and milk protein content, and increased milk fat and lactose content. Milk N efficiency decreased with ILV compared with SAL, EAAC, and GR1+ILV. Milk urea concentration was not affected by essential amino acid (EAA) infusions. Plasma urea concentration did not differ between EAAC and SAL, tended to increase with ILV and GR1+ILV over SAL, and increased with GR1+ALT compared with EAAC and SAL. In conclusion, removing Arg, Lys, and Thr or removing Ile, Leu, and Val from a complete EAA profile when the total amount of EAA infused remained constant did not impair milk production, but milk N efficiency decreased when Ile, Leu, and Val were absent. Infusion of only Ile, Leu, and Val decreased milk protein yield and content and reduced milk N efficiency compared with a complete EAA profile.

Parenteral amino acid supplementation with high-dose insulin prevents hypoaminoacidemia during cardiac surgery.

Surgery triggers a stress response that produces insulin resistance and hyperglycemia. During cardiac surgery, the administration of high-dose insulin along with dextrose titration maintains normoglycemia, but dramatically decreases plasma amino acids (AAs) compared with preoperative fasting levels. Hypoaminoacidemia limits protein synthesis and prevents anabolic responses after surgery. We investigated whether parenteral infusion of AAs during and immediately after cardiac surgery would prevent hypoaminoacidemia in patients who receive high-dose insulin therapy. Sixteen patients undergoing coronary artery bypass grafting surgery were randomly allocated to receive AAs with % kcal equivalent to either 20% (n = 8) or 35% (n = 8) of their measured resting energy expenditure (REE). Insulin was infused at a constant rate of 5 mU/(kg × min), whereas dextrose was titrated to maintain normoglycemia during and until 5 h after surgery. Plasma AA concentrations were measured at baseline before and after surgery. Compared with the 20% AA group after surgery, AA concentrations were significantly higher in the 35% AA group for 12 of 20 AAs (P < 0.032), including all branched-chain AAs. In the 20% AA group, total essential AAs decreased by 21% and nonessential AAs decreased by 14% after surgery compared with preoperative fasting levels. In contrast, giving 35% AAs prevented this unfavorable decrease in AAs, and in fact allowed for a 23% and 12% increase in essential and nonessential AAs, respectively. AA supplementation at 35% REE, but not 20% REE, can effectively prevent hypoaminoacidemia caused by high-dose insulin therapy during cardiac surgery.

Effects of jugular infusions of isoleucine, leucine, methionine, threonine, and other amino acids on insulin and glucagon concentrations, mammalian target of rapamycin (mTOR) signaling, and lactational performance in goats

The supply and profile of absorbed AA may affect milk protein synthesis through hormonal changes and mammalian target of rapamycin (mTOR) signaling pathways; and Ile, Leu, Met, and Thr (ILMT) are the 4 AA that have been reported to have the greatest effect on mammary mTOR signaling. The extent to which ILMT and the other remaining AA (RAA) differ in their effects on milk protein synthesis needs to be systematically investigated. In this study, 5 lactating goats, averaging 120 ± 10 d in milk, fitted with jugular vein and carotid artery catheters, were fasted for 24 h, followed by intravenous infusions of a mixture containing AA and glucose for 8 h in a 5 × 5 Latin square design. The AA mixtures were formulated according to the profile of casein. The amounts of AA infused were calculated based on supplies of AA when metabolizable protein (MP) was at requirement (MR). Treatments were an infusate containing glucose without AA (NTAA); an infusate containing 3 × the MR of Ile, Leu, Met and Thr (3F0R); and infusates containing 3F0R plus 1, 2, or 3 × MR of RAA (3F1R, 3F2R, and 3F3R, respectively) according to amounts provided when fed to meet MP requirements for maintenance and lactation for each goat. Milk, arterial blood, and mammary tissue samples were collected immediately after halting the infusion. Relative to NTAA, supplementation of ILMT tended to increase milk protein production and plasma glucose concentrations, and increased milk and lactose production, but had no effects on production or content of milk fat. Graded supplementation of RAA tended to quadratically affect production of milk and lactose. Arterial glucose and glucagon concentrations decreased linearly, and plasma insulin concentrations decreased quadratically with increased RAA. Mammary p70-S6K1 phosphorylation was decreased by addition of ILMT compared with NTAA but increased linearly with increased RAA infusion. Furthermore, EIF4EBP1 gene expression was much lower for 3F-treated goats than for the NTAA treatment. Both MTOR and RPS6KB1 gene expressions were decreased quadratically with increased RAA supply. These results suggested that short-term milk protein yield tended to be increased by elevated ILMT availability, and this trend was not explained by variations in mammary mTOR signaling or pancreatic hormone secretions, whereas graded increase of RAA in combination with ILMT appeared to regulate the efficiency of conversion of glucose to lactose in a manner not involving milk protein production.

Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors.

Protein intake robustly stimulates the secretion of the incretin hormone, glucagon‐like peptide‐1 (GLP‐1) but the molecular mechanisms involved are not well understood. In particular, it is unknown whether proteins stimulate secretion by activation of luminal or basolateral sensors. We characterized the mechanisms using a physiologically relevant model – the isolated perfused proximal rat small intestine. Intraluminal protein hydrolysates derived from meat (peptone; 50 mg/mL) increased GLP‐1 secretion 2.3‐fold (from a basal secretion of 110 ± 28 fmol/min). The sensory mechanisms underlying the response depended on di/tripeptide uptake through Peptide Transporter 1 (PepT1) and subsequent basolateral activation of the amino acid sensing receptor, Calcium‐Sensing Receptor (CaSR), since inhibition of PepT1 as well as CaSR both attenuated the peptone‐induced GLP‐1 response. Supporting this, intraluminal peptones were absorbed efficiently by the perfused intestine (resulting in increased amino acid concentrations in the venous effluent) and infusion of amino acids robustly stimulated GLP‐1 secretion. Inhibitors of voltage‐gated L‐type Ca2+ channels had no effect on secretion suggesting that peptone‐mediated GLP‐1 secretion is not mediated by L‐cell depolarization with subsequent opening of these channels. Specific targeting of CaSR could serve as a target to stimulate the endogenous secretion of GLP‐1.

Protein malnutrition prevents heat conservation induced by amino acid infusion during general anesthesia in rats

The intravenous administration of an amino acid (AA) mixture during general anesthesia reduces anesthesia-induced hypothermia. AA-induced skeletal muscle protein synthesis and thermogenesis play important roles in the antihypothermic effects of AAs. We hypothesized that a preanesthetic dietary protein deficiency impairs the antihypothermic effects of AAs during general anesthesia due to a reduction in thermogenesis caused by a decrease in muscle protein synthesis. Sprague-Dawley rats were divided into 4 groups: fed a control diet plus saline (CON-SAL) or the AA mixture (CON-AA), and fed a protein-free diet plus saline (PF-SAL) or the AA mixture (PF-AA). SAL solution or AA mixture solution was infused for 180 minutes during sevoflurane anesthesia, and rectal temperatures were measured. Rectal temperatures were significantly higher in the CON-AA group than in the PF-AA group 90 to 180 minutes after initiating the intravenous infusion of the test solutions. There was no significant difference between the PF-SAL and PF-AA groups. Plasma insulin concentrations were significantly higher in the CON-AA group than in the PF-AA group (P < .05). The phosphorylation states of protein kinase B, mammalian target of rapamycin, and eukaryotic initiation factor 4E-binding protein 1 were significantly greater in the CON-AA group than in the PF-AA group (P < .05, P < .05, and P < .01, respectively). Our results indicated that a dietary protein deficiency before general anesthesia impaired the antihypothermic effects of an AA mixture infusion during general anesthesia by decreasing muscle protein synthesis through the insulin-stimulated phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin complex 1 signaling pathway followed by metabolic heat production.