Shared control of hepatic glycogen synthesis by glycogen synthase and glucokinase

Gomis, Roger R.; Ferrer, Juan Carlos; Guinovart, Joan J.

doi:10.1042/bj3510811

Cited by 39 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3C) and glycogen content (31.7 Ϯ 3.4 and 67.2 Ϯ 6.9 g/10 6 cells, respectively) (Fig. 3A) of AdCMV-GK-infected hepatocytes treated with 5 or 25 mM glucose also rose significantly and in a glucose-concentration dependent manner, as described previously (1).…”

Section: Resultssupporting

confidence: 86%

Glucose 6-Phosphate Produced by Gluconeogenesis and by Glucokinase Is Equally Effective in Activating Hepatic Glycogen Synthase

Gomis

Favre

Garcı́a-Rocha

et al. 2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Glucose 6-phosphate (Glc-6-P) produced in cultured hepatocytes by direct phosphorylation of glucose or by gluconeogenesis from dihydroxyacetone (DHA) was equally effective in activating glycogen synthase (GS). However, glycogen accumulation was higher in hepatocytes incubated with glucose than in those treated with DHA. This difference was attributed to decreased futile cycling through GS and glycogen phosphorylase (GP) in the glucose-treated hepatocytes, owing to the partial inactivation of GP induced by glucose. Our results indicate that the gluconeogenic pathway and the glucokinasemediated phosphorylation of glucose deliver their common product to the same Glc-6-P pool, which is accessible to liver GS. As observed in the treatment with glucose, incubation of cultured hepatocytes with DHA caused the translocation of GS from a uniform cytoplasmic distribution to the hepatocyte periphery and a similar pattern of glycogen deposition. We hypothesize that Glc-6-P has a major role in glycogen metabolism not only by determining the activation state of GS but also by controlling its subcellular distribution in the hepatocyte.

show abstract

Section: Resultssupporting

confidence: 86%

Glucose 6-Phosphate Produced by Gluconeogenesis and by Glucokinase Is Equally Effective in Activating Hepatic Glycogen Synthase

Gomis

Favre

Garcı́a-Rocha

et al. 2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Only when blood sugar concentration increases above a threshold level does GK translocate to the cytosol and start to produce Glc-6-P, thus giving the signal that triggers the synthesis of hepatic glycogen. In this case, the control of glycogen synthesis is not exerted by glucose transport but rather by GK and GS (8). It appears that the inability of the Glc-6-P produced by HK I to stimulate the activation of LGS is one way for the hepatocyte to ensure that hepatic glycogen synthesis is only engaged when needed, that is when blood glucose levels are high.…”

Section: Discussionmentioning

confidence: 95%

“…The nitrocellulose blot was incubated overnight at 4°C in blocking buffer (1% bovine serum albumin, 0.05% Tween 20 in phosphate-buffered saline). The blot was then incubated for 1 h at room temperature with a rabbit antibody against rat LGS (8), human MGS (14), or rat GK (21) or a mouse antibody against rat HK I (Chemicon), washed, and then incubated for 1 h with a secondary anti-rabbit (Amersham Biosciences) or anti-mouse (Dako, Glostrup, Denmark) antibody conjugated to horseradish peroxidase. Immunoreactive bands were visualized using an ECL kit (Amersham Biosciences) following the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…This is attributed to a different capacity of Glc-6-P produced by GK or HK I to induce the activation of liver glycogen synthase (LGS) (7). Further studies in cultured hepatocytes have shown that LGS shares the control of glycogen synthesis with GK (8). In contrast, the control of glycogen deposition from glucose in muscle is shared between glucose transport and muscle glycogen synthase (MGS) (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Liver Glycogen Synthase but Not the Muscle Isoform Differentiates between Glucose 6-Phosphate Produced by Glucokinase or Hexokinase

Gomis¹,

Cid²,

Garcı́a-Rocha

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Using adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, we have overexpressed hexokinase I (HK I), glucokinase (GK), liver glycogen synthase (LGS), muscle glycogen synthase (MGS), and combinations of each of the two glucose-phosphorylating enzymes with each one of the GS isoforms. FTO-2B cells do not synthesize glycogen even when incubated with high doses of glucose. Adenovirus-induced overexpression of HK I and/or LGS, two enzymes endogenously expressed by these cells, did not produce a significant increase in the levels of active GS and the total glycogen content. In contrast, GK overexpression led to the glucosedependent activation of endogenous or overexpressed LGS and to the accumulation of glycogen. Similarly overexpressed MGS was efficiently activated by the glucose-6-phosphate (Glc-6-P) produced by either endogenous or overexpressed HK I and by overexpressed GK. These results indicate the existence of at least two pools of Glc-6-P in the cell, one of them is accessible to both isoforms of GS and is replenished by the action of GK, whereas LGS is excluded from the cellular compartment where the Glc-6-P produced by HK I is directed. These findings are interpreted in terms of the metabolic role that the two pairs of enzymes, HK I-MGS in the muscle and GK-LGS in the hepatocyte, perform in their respective tissues.

show abstract

“…Glucose transport and phosphorylation are the first steps in glucose utilization in the liver, where GK contributes to glucose disposal. Several studies in vitro have shown that GK activation is needed for glycolysis and glycogen synthesis [1,2,3,4]. Similarly, in transgenic liquid N 2 .…”

mentioning

confidence: 96%

Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance

et al. 2003

View full text Add to dashboard Cite

Aims/hypothesis. Glucokinase overexpression in the liver increases glucose uptake and utilization, and improves glucose tolerance in young transgenic mice. Here, we examined the long-term effects of hepatic overexpression of glucokinase on glucose homeostasis. Moreover, we determined whether glucokinase overexpression counteracted high-fat diet-induced insulin resistance. Methods. Transgenic mice overexpressing glucokinase in liver under the control of the phosphoenolpyruvate carboxykinase promoter, fed either a standard diet or a high-fat diet, were studied. We used non-transgenic littermates as controls. Results. Transgenic mice over 6 months old developed impaired glucose tolerance. In addition, at 12 months of age, transgenic mice showed mild hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. In spite of increased glucokinase activity, the liver of these mice accumulated less glycogen and increased triglyceride deposition. When 2-month-old glucose-tolerant mice were fed a high-fat diet, transgenic mice gained more body weight and became hyperglycaemic and hyperinsulinaemic. This was concomitant to glucose intolerance, liver steatosis and whole-body insulin resistance. Conclusion/interpretation. Long-term overexpression of glucokinase increases hepatic lipogenesis and circulating lipids, which lead to insulin resistance. Our results also suggest that the liver plays a key role in the onset of diabetes. [Diabetologia (2003) mice overexpressing GK in the liver, intracellular glucose 6-phosphate, glycogen and L-pyruvate kinase activity are increased, indicating that the activation of GK can induce glycolysis and glycogen synthesis in vivo [5]. These transgenic mice have reduced glycaemia, insulinaemia and blood glucose after an intraperitoneal glucose tolerance test, indicating that GK overexpression increased blood glucose disposal by the liver [5]. Similar results have also been obtained in transgenic mice expressing the human GK gene in the liver [6] and in mice overexpressing one or more extra copies of the entire mouse GK gene locus [7].Since the decrease in glucokinase gene expression in diabetic animals could contribute to hyperglycaemia, the effect of hepatic GK overexpression has been studied in animal models of Type 1 and Type 2 diabetes. Thus, streptozotocin-treated GK-expressing transgenic mice maintained normal levels of GK activity, Glucokinase (GK) is the main glucose-phosphorylating enzyme in the liver and pancreatic beta cells. Glucose transport and phosphorylation are the first steps in glucose utilization in the liver, where GK contributes to glucose disposal. Several studies in vitro have shown that GK activation is needed for glycolysis and glycogen synthesis [1,2,3,4]. Similarly, in transgenic

show abstract

Shared control of hepatic glycogen synthesis by glycogen synthase and glucokinase

Cited by 39 publications

References 30 publications

Glucose 6-Phosphate Produced by Gluconeogenesis and by Glucokinase Is Equally Effective in Activating Hepatic Glycogen Synthase

Glucose 6-Phosphate Produced by Gluconeogenesis and by Glucokinase Is Equally Effective in Activating Hepatic Glycogen Synthase

Liver Glycogen Synthase but Not the Muscle Isoform Differentiates between Glucose 6-Phosphate Produced by Glucokinase or Hexokinase

Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance

Contact Info

Product

Resources

About