Musclin ;Skeletal muscle

[goose]

I got this paper a while back,I have not seen any new information,not Thrilling but intresting.Enjoy.



Bascially, the authors found a small (~11kDa) protein that appears to be secreted from skeletal muscle and is exquisitly sensitive to nutritional regulation.

In brief, the authors state:

1. Mouse cDNA for musclin encoded for 130 amino acids, including an N-terminal 30-AA signal sequence (indicating secretion).
2. Contains a region homologous to the natureitic peptide family of proteins.
3. Contains a KKKR sequence, possibly for proteolytic cleavage (again, supportive of a secreted factor)
4. Full-length and cleaved form were secreted in media of musclin cDNA-transfected cells (pretty much guarantees that we have a hormone).
5. cDNA levels in sk. muscle were VERY low during fasting (48hrs), and increased back to baseline upon feeding; were also very low in STZ-treated mice (no/few functional beta-cells).
6. Insulin increased, while epinephrine, isoproterenol, and forskolin all decreased musclin mRNA.
7. Overexpression of musclin mRNA was found in skeletal muscle of Agouti mice, as well as db/db.
8. Recombinant musclin reduced insulin-stimulated glucose transport and glycogen synthesis in myocytes.
9. No effects on myogenesis, at least in C2C12 myoblasts with respect to differentiation and proliferation.
10. IGF-1 induces musclin mRNA as well, in fully-differentiated myocytes

Another paper.

Department of Medicine, Division of Physiology, University of Fribourg, Switzerland. [email protected]

Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely: the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport),the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recentlythe stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes).This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity.




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[goose]

Bump.


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