Transcriptional activation of the IL‐6 gene in human contracting skeletal muscle: influence of muscle glycogen content

Keller, Charlotte; Steensberg, Adam; Pilegaard, Henriette; Osada, Takuya; Saltin, Bengt; Pedersen, Bente Klarlund; Neufer, P. Darrell

doi:10.1096/fj.01-0507fje

Cited by 429 publications

(444 citation statements)

References 31 publications

Supporting

Mentioning

385

Contrasting

Unclassified

Order By: Relevance

“…However, our data demonstrate that loss of GS does not affect insulin secretion in a beta cell-autonomous manner, thus implying that the high insulin response in constitutive Gys1 KO mice was probably secondary to alterations in other organs. In this regard, IL-6, which is more potently secreted by the muscle in conditions of low glycogen availability [34], has been shown to stimulate insulin release through glucagon-like peptide 1 (GLP-1)-dependent mechanisms [35]. Our data strongly support the notion that glycogen synthesis in beta cells is not relevant for the maintenance of proper glucose homeostasis.…”

Section: Discussionsupporting

confidence: 72%

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis

et al. 2016

View full text Add to dashboard Cite

Aims/hypothesis Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Methods Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreasspecific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acidSchiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Results Gys1 knockout (Gys1 KO ) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 KO and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG OE ) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG OE mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Conclusions/interpretation Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

show abstract

Section: Discussionsupporting

confidence: 72%

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…exacerbação da expressão da IL-6 35 , uma vez que esta citocina funciona como um sensor energético muscular 1 , entretanto, os estoques de glicogênio não foram avaliados no presente estudo, fato este que deve ser levado em consideração na interpretação dos resultados, e que pode ser visto como uma limitação.…”

Section: Discussionunclassified

Efeitos de diferentes intensidades de exercício sobre a concentração sérica de interleucinas

Neves

Tenório

Muniz

et al. 2014

Rev. bras. educ. fís. esporte

View full text Add to dashboard Cite

ResumoO presente estudo teve como objetivo analisar os efeitos agudos e de curta duração de duas intensidades de exercício aeróbio sobre a concentração circulante de IL-6 e IL-10. Quinze homens jovens fi sicamente ativos (21,0 ± 1,9 anos) foram submetidos a duas sessões de exercício ("crossover"): alta intensidade de exercício (AIE)-(80% VO 2 pico), e baixa intensidade de exercício (BIE)-(40% VO 2 pico), com intervalo de sete dias ("Wash out"). Amostras de sangue foram coletadas em tubos com EDTA, antes do exercício (basal), imediatamente após o exercício (agudo) e após 2 h de recuperação passiva. As concentrações séricas de IL-6 e IL-10 foram determinadas com a utilização de kits comerciais de ELISA. Os resultados demonstraram elevação aguda da IL-6, em resposta ao AIE em relação ao BIE (p < 0,05), enquanto que a IL-10 apresentou maior redução sistêmica aguda para BIE em comparação a AIE (p < 0,05). Não houve diferença na variação das citocinas após 2 h do término do exercício. Conclui-se que ambas as sessões agudas de exercício são capazes de modular a concentração circulante destas citocinas, e que a magnitude das alterações são dependentes da intensidade do esforço. PALAVRAS-CHAVE: Exercício aeróbio; Infl amação; Citocinas; Homens jovens.Um estado de in amação crônico, caracterizado pelo aumento na concentração sistêmica de algumas citocinas e proteína de fase aguda com concomitante redução da contagem de neutró los e células "natural killer" (NK) 1-2 , é um fator chave para o desenvolvimento de algumas condições patológicas 3 , tais como a resistência à insulina 4-5 e aterosclerose 6 .Por estarem envolvidas em diversas funções como angiogênese, lipólise, controle do metabolismo da glicose e regulação de processos in amatórios, citocinas como a interleucina 10 (IL-10) e a interleucina 6 (IL-6) têm recebido especial atenção por parte de diversos grupos de pesquisa [7][8] . O balanço entre a concentração circulante de citocinas pró e antiin amatórias, é considerado, um importante meio de controle da in amação crônica, estando condicionada a regulação por parte de fatores gené-ticos (polimor smos) e ao estilo de vida 9 .Dentre os fatores modi cáveis, o exercício físico ocupa um lugar de destaque, pois oferece proteção contra algumas das principais causas de morte na vida adulta, incluindo doenças cardiovasculares, diabetes tipo 2, câncer de cólon e de mama 2,10 .O efeito crônico do exercício físico sobre os processos in amatórios é re exo do somatório de diversas ações antiin amatórias promovidas pelas sessões de exercícios (efeito agudo) 1 . Classicamente, acredita-se que em resposta ao esforço físico, ocorram incrementos na produção da IL-6, com consequente disparo de uma cascata antiin amatória, efetivada pela elevação nos níveis circulantes de IL-10, do receptor antagonista da interleucina -1 (IL-1ra) e do receptor solúvel do

show abstract

“…These pathways mediate increased glucose uptake, GLUT4 translocation and glycogen synthesis on acute exposure to IL-6 (Table 1) [18][19][20]. Interestingly, ingestion of glucose during exercise blunts IL-6 secretion from contracting muscle [21], and a low pre-exercise muscular glycogen level augments the induction of IL-6 expression and release by exercise [11,22]. Exercise-induced adaptation in skeletal muscle also includes an increase in pre-exercise muscular glycogen content.…”

Section: Myokines and Metabolic Regulationmentioning

confidence: 99%

Myokines in insulin resistance and type 2 diabetes

et al. 2014

View full text Add to dashboard Cite

Skeletal muscle represents the largest organ of the body in non-obese individuals and is now considered to be an active endocrine organ releasing a host of so-called myokines. These myokines are part of a complex network that mediates communication between muscle, the liver, adipose tissue, the brain and other organs. Recent data suggest that myokines regulated by muscle contraction may play a key role in mediating the health-promoting effects of regular physical activity. Although hundreds of myokines have recently been described in proteomic studies, we currently have a rather limited knowledge of the specific role these myokines play in the prevention of insulin resistance, inflammation and associated metabolic dysfunction. Several myokines are known to have both local and endocrine functions, but in many cases the contribution of physical activity to the systemic level of these molecules remains as yet unexplored. Very recently, novel myokines such as irisin, which is thought to induce a white to brown shift in adipocytes, have gained considerable interest as potential therapeutic targets. In this review, we summarise the most recent findings on the role of myokines in the regulation of substrate metabolism and insulin sensitivity. We further explore the role of myokines in the regulation of inflammation and provide a critical assessment of irisin and other myokines regarding their potential as therapeutic targets.

show abstract

Transcriptional activation of the IL‐6 gene in human contracting skeletal muscle: influence of muscle glycogen content

Cited by 429 publications

References 31 publications

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis

Efeitos de diferentes intensidades de exercício sobre a concentração sérica de interleucinas

Myokines in insulin resistance and type 2 diabetes

Contact Info

Product

Resources

About