Dataset Information

SOCS-3 in muscle

ABSTRACT: Aims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined. Methods We generated transgenic mice constitutively expressing SOCS-3 in skeletal muscle to define whether the sole expression of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism. Results We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 expression, several genes had deregulated expression, among them other members of the SOCS family. This could maintain the insulin signal into skeletal muscle. Interestingly, we found that SOCS-3 interacts with calcineurin, which has been implicated in muscle contractility. In SOCS-3 transgenic muscle, this leads to delocalisation of calcineurin to the fibre periphery. Relevant to this finding, SOCS-3 transgenic animals had dilatation of the sarcoplasmic reticulum associated with swollen mitochondria and decreased voluntary activity. Conclusions/interpretation Our results show that constitutive SOCS-3 expression in skeletal muscle is not in itself sufficient to induce the establishment of metabolic disorders such as diabetes. In contrast, we reveal a novel role of SOCS-3, which appears to be important for muscle integrity and locomotor activity. (Patricia Lebrun et al, Diabetologia, 2009)

ORGANISM(S): Mus musculus

PROVIDER: GSE17063 | GEO | 2009/12/31

SECONDARY ACCESSION(S): PRJNA119841

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Physical inactivity and western diet are the main factors leading to skeletal muscle (and whole-body) insulin resistance – a defect in insulin-mediated glucose uptake and metabolism – and associated metabolic diseases, such as obesity and type 2 diabetes mellitus (T2D). The study of the response to a mixed meal (normalized for body mass and/or basal metabolic rate) is of particular interest, as it simulates the physiological response to a typical (daily) single meal that depends on both the secretory function of the beta cells (insulin response) and the sensitivity of skeletal muscle signaling to insulin – variables, which markedly changing during development of insulin resistance and T2D. We aimed to compare the early transcriptomic response to a mixed meal normalized to body mass in skeletal muscle of healthy subjects and obese patients without (Ob) and with T2D (Ob+T2D). To investigate the early transcriptomic response we took biopsy samples from the vastus lateralis muscle prior to and 1 h after a meal. In the Ob+T2D group the average level and increase in C-peptide and insulin in the blood were comparable with healthy subjects that, apparently, is explained by dysfunction of the beta-cells induced by chronic T2D. At the same time, the Ob+T2D group demonstrated dysregulation of mixed meal-induced gene expression in skeletal muscle: morу than two times lower number of DEGs and a small overlapping with the gene response in the control group. On the contrary, the postprandial level of C-peptide and insulin in the Ob group was significantly greater than in healthy control that is related to insulin oversecretion associated with insulin resistance. Despite this, the gene response in skeletal muscle was also significantly dysregulated; moreover, it differed from the response in the Ob+T2D group. It means that defect in regulation of insulin-induced gene expression (insulin resistance in terms of gene expression) appears at the first stage of the development of metabolic disorders.

Dataset Information

SOCS-3 in muscle

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets