Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes

Dietze, Daniela; Koenen, Marlis; Röhrig, K.; Horikoshi, Hiroyoshi; Hauner, Hans; Eckel, Jürgen

doi:10.2337/diabetes.51.8.2369

Cited by 158 publications

(131 citation statements)

References 47 publications

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“…Culture of human skeletal muscle cells HSkMC isolated from rectus abdominis muscle of six healthy white donors (three male donors of 16, 18, and 21 years of age, and three female donors of 25, 33 and 37 years of age) were supplied as proliferating myoblasts from PromoCell (Heidelberg, Germany) or Lonza (Basel, Switzerland) and cultured as described previously [27]. Briefly, myoblasts were seeded in six-well culture dishes and were cultured in growth medium containing α-modified Eagle's (αMEM)/Ham's F-12 medium (Gibco, Berlin, Germany) and the supplement pack for skeletal muscle cells from PromoCell.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of PRAS40 inhibits insulin action via proteasome-mediated degradation of IRS1 in primary human skeletal muscle cells

Wiza

Nascimento

et al. 2013

Diabetologia

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Aims/hypothesis The proline-rich Akt substrate of 40 kDa (PRAS40) is a component of the mammalian target of rapamycin complex 1 (mTORC1) and among the most prominent Akt substrates in skeletal muscle. Yet the cellular functions of PRAS40 are incompletely defined. This study assessed the function of PRAS40 in insulin action in primary human skeletal muscle cells (hSkMC). Methods Insulin action was examined in hSkMC following small interfering RNA-mediated silencing of PRAS40 (also known as AKT1S1) under normal conditions and following chemokine-induced insulin resistance. Results PRAS40 knockdown (PRAS40-KD) in hSkMC decreased insulin-mediated phosphorylation of Akt by 50% (p<0.05) as well as of the Akt substrates glycogen synthase kinase 3 (40%) and tuberous sclerosis complex 2 (32%) (both p<0.05). Furthermore, insulin-stimulated glucose uptake was reduced by 20% in PRAS40-KD myotubes (p<0.05). Exposing PRAS40-KD myotubes to chemokines caused no additional deterioration of insulin action. PRAS40-KD further reduced insulin-mediated phosphorylation of the mTORC1-regulated proteins p70S6 kinase (p70S6K) (47%), S6 (43%), and eukaryotic elongation 4E-binding protein 1 (100%), as well as protein levels of growth factor receptor bound protein 10 (35%) (all p<0.05). The inhibition of insulin action in PRAS40-KD myotubes was associated with a reduction in IRS1 protein levels (60%) (p<0.05), and was reversed by pharmacological proteasome inhibition. Accordingly, expression of the genes encoding E3-ligases Fbox protein 32 (also known as atrogin-1) and muscle RINGfinger protein-1 and activity of the proteasome was elevated in PRAS40-KD myotubes. Conclusions/interpretation Inhibition of insulin action in PRAS40-KD myotubes was found to associate with IRS1 degradation promoted by increased proteasome activity rather than hyperactivation of the p70S6K-negative-feedback loop. These findings identify PRAS40 as a modulator of insulin action.

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Section: Methodsmentioning

confidence: 99%

Knockdown of PRAS40 inhibits insulin action via proteasome-mediated degradation of IRS1 in primary human skeletal muscle cells

Wiza

Nascimento

et al. 2013

Diabetologia

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“…In addition, results obtained from isolated cell systems should be treated with some caution, because they are not representative of multi-organ systems. Indeed, even when different cell types, for example adipocytes and myocytes, are co-cultured and subjected to a pharmacological intervention, the results obtained are different from those obtained through culturing the cell types in isolation and subjecting them to the identical intervention [75].…”

Section: Interaction Between Il-6 and Glucose Transport In Vitromentioning

confidence: 95%

Interleukin-6 and insulin sensitivity: friend or foe?

2004

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“…Interaction between adipocytes and myoblasts in the very early stages of growth is likely to occur and influences the respective differentiation of both cellular types. As an example, impairment of insulin signalling has been demonstrated in muscle cells by in vitro coculture with human adipocytes (Dietze et al, 2002). Then, the activity of adipocytes in secreting adipokines (such as leptin; Kokta et al, 2004) as well as that of muscle fibres secreting myokines (such as myostatin, Artaza et al, 2005;Hirai et al, 2007) are among the key putative mechanisms of this interaction.…”

Section: How Might Marbling Begin?mentioning

confidence: 99%

Intramuscular fat content in meat-producing animals: development, genetic and nutritional control, and identification of putative markers

Hocquette

Gondret

Baéza³

et al. 2010

Animal

654

447

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Intramuscular fat (IMF) content plays a key role in various quality traits of meat. IMF content varies between species, between breeds and between muscle types in the same breed. Other factors are involved in the variation of IMF content in animals, including gender, age and feeding. Variability in IMF content is mainly linked to the number and size of intramuscular adipocytes. The accretion rate of IMF depends on the muscle growth rate. For instance, animals having a high muscularity with a high glycolytic activity display a reduced development of IMF. This suggests that muscle cells and adipocytes interplay during growth. In addition, early events that influence adipogenesis inside the muscle (i.e proliferation and differentiation of adipose cells, the connective structure embedding adipocytes) might be involved in interindividual differences in IMF content. Increasing muscularity will also dilute the final fat content of muscle. At the metabolic level, IMF content results from the balance between uptake, synthesis and degradation of triacylglycerols, which involve many metabolic pathways in both adipocytes and myofibres. Various experiments revealed an association between IMF level and the muscle content in adipocyte-type fatty acid-binding protein, the activities of oxidative enzymes, or the delta-6-desaturase level; however, other studies failed to confirm such relationships. This might be due to the importance of fatty acid fluxes that is likely to be responsible for variability in IMF content during the postnatal period rather than the control of one single pathway. This is evident in the muscle of most fish species in which triacylglycerol synthesis is almost zero. Genetic approaches for increasing IMF have been focused on live animal ultrasound to derive estimated breeding values. More recently, efforts have concentrated on discovering DNA markers that change the distribution of fat in the body (i.e. towards IMF at the expense of the carcass fatness). Thanks to the exhaustive nature of genomics (transcriptomics and proteomics), our knowledge on fat accumulation in muscles is now being underpinned. Metabolic specificities of intramuscular adipocytes have also been demonstrated, as compared to other depots. Nutritional manipulation of IMF independently from body fat depots has proved to be more difficult to achieve than genetic strategies to have lipid deposition dependent of adipose tissue location. In addition, the biological mechanisms that explain the variability of IMF content differ between genetic and nutritional factors. The nutritional regulation of IMF also differs between ruminants, monogastrics and fish due to their digestive and nutritional particularities.

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Impairment of Insulin Signaling in Human Skeletal Muscle Cells by Co-Culture With Human Adipocytes

Cited by 158 publications

References 47 publications

Knockdown of PRAS40 inhibits insulin action via proteasome-mediated degradation of IRS1 in primary human skeletal muscle cells

Knockdown of PRAS40 inhibits insulin action via proteasome-mediated degradation of IRS1 in primary human skeletal muscle cells

Interleukin-6 and insulin sensitivity: friend or foe?

Intramuscular fat content in meat-producing animals: development, genetic and nutritional control, and identification of putative markers

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