Insulin modulates energy and substrate sensing and protein catabolism induced by chronic peritonitis in skeletal muscle of neonatal pigs

Manjarín, Rodrigo; Suryawan, Agus; Koo, Sue Jie; Wilson, Frederick A.; Nguyen, Hanh V.; Davis, Teresa A.; Orellana, Renán A.

doi:10.1038/pr.2016.129

Cited by 5 publications

(4 citation statements)

References 32 publications

(62 reference statements)

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“…Longissimus dorsi muscle is a good tissue target for measuring energy sensing and insulin signaling (Manjarín et al, 2016). Insulin is a peptide hormone that activates PI 3-kinase signaling, which, through conversion of PIP 2 to PIP 3 , recruits PDK1 to the plasma membrane with resultant phosphorylation of AKT and subsequent translocation of GLUT4 to the plasma membrane of skeletal muscle.…”

Section: Muscle Plasma Membrane Glut4 Concentrationmentioning

confidence: 99%

Effect of phytase on intestinal phytate breakdown, plasma inositol concentrations, and glucose transporter type 4 abundance in muscle membranes of weanling pigs1

Kühn

Bedford

et al. 2019

Journal of Animal Science

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The objective of this present study was to determine the effects of phytase dosing on growth performance, mineral digestibility, phytate breakdown, and the level of glucose transporter type 4 (GLUT4) in muscle plasma membranes of weanling pigs. A total of 160 barrows were used in a randomized completely block design and assigned to 4 treatments for a 7-wk study. Depending on the feeding phase, diets differed in dietary calcium (Ca) and phosphorus (P) levels (positive control [PC]: 8 to 6.8g/kg Ca; 7.3 to 6.3 g/kg P; negative control [NC]: 5.5 to 5.2 g/kg Ca; 5.4 to 4.7 g/kg P). NC diets were supplemented with phytase at 0 (NC); 500 (NC + 500 FTU); or 2,000 FTU/kg (NC + 2,000 FTU) phytase units/kg. Blood was collected after fasting (day 48) or feeding (day 49) for measurement of plasma inositol concentrations. On day 49, 2 pigs per pen were euthanized, and duodenal and ileal digesta samples were collected to determine inositol phosphates (InsP6-2) concentrations. High phytase supplementation increased BW on days 21, 35, and 49 (P < 0.05). Over the entire feeding period, ADG, ADFI, and feed efficiency were increased by NC + 2,000 FTU compared with the other treatments (P < 0.05). Postprandial plasma inositol concentration was increased in NC + 2,000 (P < 0.01), but there was only a tendency (P = 0.06) of a higher fasting plasma inositol concentration in this group. Inositol concentrations in the portal vein plasma (day 49) were not different among treatments. Duodenal digesta InsP5 and InsP6 concentrations were similar in PC and NC, but higher in these 2 treatments (P < 0.05) than those supplemented with phytase. Phytase supplementation decreased InsP6-4, resulting in increased InsP3-2 and myo-inositol concentrations. Similar effects were found in ileal contents. Compared with NC, phytase supplementation resulted in greater cumulative InsP6-2 disappearance (93.6% vs. 72.8% vs. 25.0%, for NC + 2,000 FTU, NC + 500 FTU and NC, respectively, P < 0.01) till the distal ileum. Longissimus dorsi muscle plasma membrane GLUT4 concentration was increased by NC + 2,000 FTU (P < 0.01) compared with NC. In summary, high phytase supplementation increased growth performance of nursery pigs. The higher myo-inositol release from phytate could contribute to the increased expression of GLUT4 in muscle plasma membranes. Further investigation is needed to determine whether this is associated with enhanced cellular glucose uptake and utilization.

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Section: Muscle Plasma Membrane Glut4 Concentrationmentioning

confidence: 99%

Effect of phytase on intestinal phytate breakdown, plasma inositol concentrations, and glucose transporter type 4 abundance in muscle membranes of weanling pigs1

Kühn

Bedford

et al. 2019

Journal of Animal Science

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“…In this context, is should be mentioned that mitochondrial dysfunction itself can lead to insulin resistance [ 179 ]. Not only in chronic disease, but also in acute conditions of critical illness, insulin resistance has been linked to impaired mitochondrial biogenesis [ 180 ]. The phenomenon of insulin resistance was highlighted as a metabolic hallmark feature in critical illness myopathy and ICUAW [ 90 , 181 , 182 ].…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Klawitter

Ehler

Bajorat

et al. 2023

IJMS

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Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.

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“…Neonatal/juvenile porcine models have also been developed to mimic inflammatory processes in humans. For example, neonatal pigs were used to develop a model of chronic peritonitis by ligating and puncturing the cecum, with the goal of testing the effects of insulin on muscle protein metabolism [ 238 ]. More extreme cases of inflammation may lead to endotoxic shock, which can be reproduced in pediatric pig models by the administration of lipopolysaccharides [ 239 , 240 ] or E. Coli endotoxin [ 241 ].…”

Section: Fields Of Applicationmentioning

confidence: 99%

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

et al. 2020

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Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point. This review summarizes the comparative postnatal development of pigs and humans and discusses the advantages of the juvenile pig in view of developmental pharmacology, pediatric diseases, drug discovery and drug safety testing. Furthermore, limitations and unexplored aspects of this large animal model are covered. At this point in time, the potential of the neonatal and juvenile pig as nonclinical safety models for pediatric drug development is underexplored.

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Insulin modulates energy and substrate sensing and protein catabolism induced by chronic peritonitis in skeletal muscle of neonatal pigs

Cited by 5 publications

References 32 publications

Effect of phytase on intestinal phytate breakdown, plasma inositol concentrations, and glucose transporter type 4 abundance in muscle membranes of weanling pigs1

Effect of phytase on intestinal phytate breakdown, plasma inositol concentrations, and glucose transporter type 4 abundance in muscle membranes of weanling pigs1

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

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