The rate of substrate cycling between fructose 6-phosphate and fructose 1,6-bisphosphate in skeletal muscle from cold-exposed, hyperthyroid or acutely exercised rats

Challis, R. A. John; Arch, Jonathan R.S.; Newsholme, Eric A.

doi:10.1042/bj2310217

Cited by 20 publications

(9 citation statements)

References 17 publications

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“…For example, PEP carboxykinase, expressed in adipose tissue, is part of the pathway of glyceroneogenesis in this organ (29,58). In some muscles, fructose-1,6-diphosphatase is a component of a substrate cycle that regulates the rate of glycolysis (12). The four gluconeogenic enzymes (Figure 1) are expressed in the small intestine of suckling rats, mice, and rabbits (2,27,28,67,69), but their activities decrease to very low levels after weaning.…”

Section: Activities Of Gluconeogenic Enzymes In Tissues Other Than LImentioning

confidence: 99%

Is There Glucose Production Outside of the Liver and Kidney?

Previs

Brunengraber

2009

Annu. Rev. Nutr.

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This review analyzes the evidence presented to support the role of organs other than the liver and kidney to release substantial amounts of glucose into the mammalian blood circulation. The evidence includes (a) the identification of gluconeogenic enzyme activities in various organs, especially the small intestine, (b) levels of mRNA for the same enzymes, and (c) measurements of gluconeogenic flux in the small intestine. The latter would be the definite proof of extrahepatic, extrarenal glucose production. We critically evaluate the radioactive and stable isotopic techniques used to measure intestinal gluconeogenesis. We also simulate the impact of unavoidable measurement errors on apparent rates of intestinal gluconeogenesis. We conclude that there is so far no credible evidence to support the concept that glucose can be produced by the intestine or by muscle.

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Section: Activities Of Gluconeogenic Enzymes In Tissues Other Than LImentioning

confidence: 99%

Is There Glucose Production Outside of the Liver and Kidney?

Previs

Brunengraber

2009

Annu. Rev. Nutr.

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“…A hypothesis was proposed by Newsholme in 1976 that the futile cycle between fructose-6-phosphate and fructose-1,6-bisphosphate mediated by Fbp2 could regulate whole-body thermal homeostasis 18 . Furthermore, the activity of Fbp2 has been known to be increased by cold challenge 19 as well as translocated to the mitochondria by glycogen synthase kinase 3 inhibition 20,21 , suggesting its role in thermogenesis. However, whether Fbp2 directly contributes to muscle thermogenesis in vivo and the underlying mechanisms have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

The essential role of fructose-1,6-bisphosphatase 2 enzyme in thermal homeostasis upon cold stress

et al. 2020

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Skeletal muscle is a major organ for glucose disposal and thermogenesis. While hepatic fructose-1,6-bisphosphatase is well known as a key enzyme for gluconeogenesis, the role of muscle fructose-1,6-bisphosphatase 2 (Fbp2) in glucose disposal and thermogenesis is unknown. Here, using Fbp2 knockout (KO) mice, we assessed the physiological role of Fbp2 in energy and glucose metabolism and thermogenesis. In vivo assessments of energy metabolism, glucose metabolism, and thermogenesis were performed by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and cold challenge studies, respectively. Under both feeding and fasting conditions, Fbp2 KO mice showed similar phenotypes regarding energy and glucose metabolism compared to wild-type (WT) mice. However, Fbp2 KO mice were severely intolerant to cold challenge under fasting conditions. Mechanistically, the cold-induced intramuscular conversion of lactate to glycogen (glyconeogenesis) is completely abolished in the KO muscle, which leads to a lack of glycogen source for thermogenesis in Fbp2 KO mice. The cold-intolerant phenotype of KO mice disappeared after feeding, and the KO mice were equally as cold tolerant as the WT mice and survived during the cold challenge for three weeks. Taken together, these data demonstrate that Fbp2 is essential for muscle thermogenesis by replenishing the intramuscular glycogen pool through glyconeogenesis when the exogenous glucose source is limited. These data imply the physiological importance of Fbp2 in thermal homeostasis and suggest a potential novel therapy targeted to increase glycogen replenishment upon cold stress.

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“…There is considerable evidence, provided above, which supports the view that catecholamines can stimulate the rate of substrate cycles: increased rates of cycling will not only increase sensitivity in metabolic control but will also increase the rate of thermogenesis (16). It is suggested, therefore, that the increased rate of thermogenesis under conditions when catecholamines are elevated is due, in part, to increased rates of substrate cycling.…”

Section: Insulin Resistance and Thermogenesismentioning

confidence: 89%

Some Experiments on Factors That Can Change Insulin Sensitivity

Newsholme

1990

Annals of Medicine

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Local hormones such as adenosine or prostaglandins can dramatically change the sensitivity of glucose transport in muscle to insulin. It is possible that these factors may play a role in changes in insulin sensitivity in vivo produced by such diverse conditions as treatment with furosemide, thyroid status or catecholamine status. In particular, there is evidence that chronic elevation of catecholamine or sympathetic stimulation improves insulin sensitivity. Evidence is also available to support the view that elevation of plasma catecholamine concentrations results in increased thermogenesis through activation of substrate cycling in a number of tissues. Consequently, insulin resistance and decreased thermogenesis may be explained by decreased levels of catecholamines and/or a decreased sensitivity of skeletal muscle and perhaps other tissues to catecholamines or a decreased activity of the sympathetic nervous system.

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The rate of substrate cycling between fructose 6-phosphate and fructose 1,6-bisphosphate in skeletal muscle from cold-exposed, hyperthyroid or acutely exercised rats

Cited by 20 publications

References 17 publications

Is There Glucose Production Outside of the Liver and Kidney?

Is There Glucose Production Outside of the Liver and Kidney?

The essential role of fructose-1,6-bisphosphatase 2 enzyme in thermal homeostasis upon cold stress

Some Experiments on Factors That Can Change Insulin Sensitivity

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