Insulin resistance and regulation of serum amino acid levels in myotonic dystrophy

1986 ◽  
Vol 71 (4) ◽  
pp. 429-436 ◽  
Author(s):  
Richard T. Moxley ◽  
William J. Kingston ◽  
Kenneth L. Minaker ◽  
Alastair J. Corbett ◽  
John W. Rowe
Keyword(s):  
Insulin Resistance ◽  
Amino Acid ◽  
Myotonic Dystrophy ◽  
Insulin Infusion ◽  
Normal Subjects ◽  
Amino Acid Uptake ◽  
Whole Body ◽  
Glucose Disposal ◽  
Acid Uptake ◽  
Amino Acid Levels

1. To quantify the degree of whole body insulin resistance in patients with myotonic dystrophy and to determine if these same patients display signs of a whole body decrease in the action of insulin on amino acid uptake and glucose disposal, three separate 120 min studies employing the euglycaemic insulin clamp technique (20, 80 and 200 m-units min−1 m−2) were performed on five ambulatory patients with myotonic dystrophy. The results were compared with findings obtained in identical studies in 21 normal volunteers. 2. Myotonic dystrophy patients showed a slower, less marked decline in the serum concentration of insulin sensitive amino acids (threonine, valine, leucine, isoleucine, tyrosine, phenylalanine) during all three insulin infusions compared with normals. The greatest difference occurred at the low physiological elevations of insulin produced by the 20 m-units min−1 m−2 infusion. 3. Alanine levels fell significantly below baseline in patients with myotonic dystrophy after 60 and 120 min of insulin infusion with all three rates of insulin infusion. Normal subjects had only a minimal, insignificant decline in arterialized alanine concentrations during the three different insulin infusions. 4. Creatinine adjusted rates of whole body glucose disposal were 30–40% lower in the myotonic dystrophy group at all three doses of insulin compared with the normals. This demonstrates that their insulin resistance was not due simply to a reduction in muscle mass. 5. The overall pattern of findings in these studies of patients with myotonic dystrophy indicates that there is a whole body derangement in the regulation of circulating amino acid levels by insulin as well as a marked decrease in the action of this hormone in stimulating glucose uptake by target tissues.

The role of amino acid transporters in inherited and acquired diseases

2011 ◽  
Vol 436 (2) ◽  
pp. 193-211 ◽  
Author(s):  
Stefan Bröer ◽  
Manuel Palacín
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Mammalian Cells ◽  
Neuronal Excitability ◽  
Tumour Progression ◽  
Building Blocks ◽  
Amino Acid Uptake ◽  
Whole Body ◽  
Amino Acid Transporters ◽  
Acid Uptake

Amino acids are essential building blocks of all mammalian cells. In addition to their role in protein synthesis, amino acids play an important role as energy fuels, precursors for a variety of metabolites and as signalling molecules. Disorders associated with the malfunction of amino acid transporters reflect the variety of roles that they fulfil in human physiology. Mutations of brain amino acid transporters affect neuronal excitability. Mutations of renal and intestinal amino acid transporters affect whole-body homoeostasis, resulting in malabsorption and renal problems. Amino acid transporters that are integral parts of metabolic pathways reduce the function of these pathways. Finally, amino acid uptake is essential for cell growth, thereby explaining their role in tumour progression. The present review summarizes the involvement of amino acid transporters in these roles as illustrated by diseases resulting from transporter malfunction.

Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia

1990 ◽  
Vol 259 (2) ◽  
pp. E185-E194 ◽  
Author(s):  
W. M. Bennet ◽  
A. A. Connacher ◽  
C. M. Scrimgeour ◽  
R. T. Jung ◽  
M. J. Rennie
Keyword(s):  
Amino Acid ◽  
Healthy Subjects ◽  
Amino Acid Uptake ◽  
Whole Body ◽  
Slight Reduction ◽  
Acid Uptake ◽  
Protein Breakdown ◽  
Body Protein ◽  
Kinetics Of ◽  
Stimulation Of

The effect of insulin on leg and whole body protein turnover was determined by leg exchange and plasma kinetics of [15N]phenylalanine and [1-13C]leucine during amino acid (AA) sufficiency. Eight healthy subjects were studied during AA infusion alone and during infusion of glucose and insulin (0.29 nmol.m-2.min-1) with additional AA. Insulin strongly stimulated the positive leg AA balance seen with AA (AA alone, 2.6 +/- 6.1 vs. insulin + AA, 33.1 +/- 5.8 nmol phenylalanine . 100 g leg-1.min-1; P less than 0.001). Phenylalanine uptake by leg tissues rose during insulin plus AA (47.3 +/- 11.5 vs. 73.1 +/- 7.3 nmol. 100 g-1.min-1; P = 0.022) but with only a slight reduction in leg phenylalanine release (44.7 +/- 8.1 vs. 40.0 +/- 7.9 nmol.100 g-1.min-1). Leg nonoxidative leucine plus alpha-ketoisocaproate (KIC) uptake was increased slightly with insulin (129 +/- 26 vs. 146 +/- 21 nmol.100 g-1. min-1), but leg leucine oxidation increased fourfold (P = 0.012). Leg leucine plus KIC release was reduced by insulin (120 +/- 17 vs. 84 +/- 10 nmol.100 g-1.min-1; P = 0.005); endogenous leucine appearance of leucine and phenylalanine decreased with insulin (leucine, 1.97 +/- 0.08 vs. 1.65 +/- 0.10; phenylalanine, 0.76 +/- 0.03 vs. 0.54 +/- 0.08 mumols.kg-1.min-1; P less than 0.02). The results suggest that insulin, given with sufficient amino acids, may stimulate leg and whole body protein balance by mechanisms including stimulation of protein synthesis and inhibition of protein breakdown.

Dependence of intestinal amino acid uptake on dietary protein or amino acid levels

1987 ◽  
Vol 252 (5) ◽  
pp. G614-G625 ◽  
Author(s):  
W. H. Karasov ◽  
D. H. Solberg ◽  
J. M. Diamond
Keyword(s):  
Amino Acid ◽  
Brush Border ◽  
Dietary Protein ◽  
Brush Border Membrane ◽  
Amino Acid Uptake ◽  
Multiple Roles ◽  
Acid Uptake ◽  
Imino Acid ◽  
Amino Acid Levels ◽  
High Concentrations

To understand how intestinal amino acid (AA) transport is regulated by dietary substrate levels, we measured uptake of seven AAs and glucose across the jejunal brush-border membrane of mice kept on one of three isocaloric rations differing in nitrogen content. In the high-protein ration, uptake increased by 77-81% for the nonessential, less toxic AAs, proline, and aspartate but only by 32-61% for the more toxic essential AAs tested. In the nitrogen-deficient ration, uptake decreased for the nonessential aspartate and proline but stayed constant or increased for essential AAs and for the nonessential alanine. These patterns imply independent regulation of the intestine's various AA transporters. With decreasing dietary AA (or protein), the imino acid and acidic AA "private" transporters are repressed, while activities of the basic AA transporter and the neutral AA "public" transporter decrease to an asymptote or else go through a minimum. These regulatory patterns can be understood as a compromise among conflicting constraints imposed by protein's multiple roles as a source of calories, nitrogen, and essential AAs and by the toxicity of essential AAs at high concentrations.

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

2007 ◽  
Vol 293 (5) ◽  
pp. E1393-E1398 ◽  
Author(s):  
Marietta Anderwald-Stadler ◽  
Michael Krebs ◽  
Miriam Promintzer ◽  
Martina Mandl ◽  
Martin G. Bischof ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Infusion ◽  
Plasma Concentrations ◽  
Hdl Cholesterol ◽  
Whole Body ◽  
Glucose Disposal ◽  
Insulin Resistant ◽  
Amino Acid Peptide ◽  
Fasting Plasma ◽  
Precursor Peptide

Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 ± 2 yr, BMI = 25.5 ± 0.9 kg/m2) and low (IR; n = 18, 12 females and 6 males, age 45 ± 2 yr, P = 0.49, BMI = 27.5 ± 1.1 kg/m2, P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU·min−1·m−2) isoglycemic clamp tests. M100–120 min was higher in IS (10.7 ± 0.7) than in IR (4.4 ± 0.2 mg·min−1·kg−1, P < 10−9), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 ± 6% vs. IS: 82 ± 5%, P < 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24–28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 ± 26 pg/ml vs. IS: 469 ± 23 pg/ml, P < 0.02). Clamp insulin infusion reduced plasma obestatin to ∼81% of basal values in IS ( P < 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M ( r = 0.34, P = 0.04), HDL cholesterol ( r = 0.45, P = 0.01), and plasma ghrelin concentrations ( r = 0.80, P < 0.000001) and negatively with measures of adiposity, plasma FFA during clamp ( r = −0.42, P < 0.01), and systolic blood pressure ( r = −0.33, P < 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.

scholarly journals Molecular Imaging of Brain Tumor-Associated Epilepsy

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1049
Author(s):  
Csaba Juhász ◽  
Sandeep Mittal
Keyword(s):  
Brain Tumor ◽  
Amino Acid ◽  
Brain Tumors ◽  
Treatment Strategies ◽  
Amino Acid Uptake ◽  
Seizure Outcome ◽  
Acid Uptake ◽  
Positron Emission ◽  
Oncology Practice ◽  
Glioneuronal Tumors

Epilepsy is a common clinical manifestation and a source of significant morbidity in patients with brain tumors. Neuroimaging has a pivotal role in neuro-oncology practice, including tumor detection, differentiation, grading, treatment guidance, and posttreatment monitoring. In this review, we highlight studies demonstrating that imaging can also provide information about brain tumor-associated epileptogenicity and assist delineation of the peritumoral epileptic cortex to optimize postsurgical seizure outcome. Most studies focused on gliomas and glioneuronal tumors where positron emission tomography (PET) and advanced magnetic resonance imaging (MRI) techniques can detect metabolic and biochemical changes associated with altered amino acid transport and metabolism, neuroinflammation, and neurotransmitter abnormalities in and around epileptogenic tumors. PET imaging of amino acid uptake and metabolism as well as activated microglia can detect interictal or peri-ictal cortical increased uptake (as compared to non-epileptic cortex) associated with tumor-associated epilepsy. Metabolic tumor volumes may predict seizure outcome based on objective treatment response during glioma chemotherapy. Advanced MRI, especially glutamate imaging, can detect neurotransmitter changes around epileptogenic brain tumors. Recently, developed PET radiotracers targeting specific glutamate receptor types may also identify therapeutic targets for pharmacologic seizure control. Further studies with advanced multimodal imaging approaches may facilitate development of precision treatment strategies to control brain tumor-associated epilepsy.

scholarly journals Polyribonucleotide Synthesis and Bacterial Amino Acid Uptake: the Work of Leon A. Heppel

2007 ◽  
Vol 282 (18) ◽  
pp. e13-e15
Author(s):  
Nicole Kresge ◽  
Robert D. Simoni ◽  
Robert L. Hill
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake

scholarly journals Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 125
Author(s):  
Uğur Kahya ◽  
Ayşe Sedef Köseer ◽  
Anna Dubrovska
Keyword(s):  
Amino Acid ◽  
Cancer Metabolism ◽  
Tumor Imaging ◽  
Redox Homeostasis ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Tumor Evolution ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

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