Binding and translocation of glucokinase in hepatocytes

Agius, Loranne; Peak, Matthew

doi:10.1042/bst0250145

Cited by 22 publications

(17 citation statements)

References 9 publications

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“…These data suggest that FFA induce hepatic insulin resistance at the site of glucokinase. We speculate that FFA decrease insulin-induced glucokinase translocation (an effect that is possibly mediated by PKC-␦) (67), because insulin-potentiated glucose-induced glucokinase translocation and palmitic acid partially counteracted glucose-induced glucokinase translocation in hepatocytes (2). However, high-fat feeding induced hepatic insulin resistance at the site of glucose-6-phosphatase in 5-h-fasted rats (91).…”

Section: Hepatic Glucokinase and Glucose-6-phosphatasementioning

confidence: 99%

Mechanisms of the free fatty acid-induced increase in hepatic glucose production

Lam

Carpentier

Lewis

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

236

149

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nisms of the free fatty acid-induced increase in hepatic glucose production. Am J Physiol Endocrinol Metab 284: E863-E873, 2003; 10.1152/ajpendo.00033.2003.-The associations between obesity, insulin resistance, and type 2 diabetes mellitus are well documented. Free fatty acids (FFA), which are often elevated in obesity, have been implicated as an important link in these associations. Contrary to muscle glucose metabolism, the effects of FFA on hepatic glucose metabolism and the associated mechanisms have not been extensively investigated. It is still controversial whether FFA have substantial effects on hepatic glucose production, and the mechanisms responsible for these putative effects remain unknown. We review recent progress in this area and try to clarify controversial issues regarding the mechanisms responsible for the FFA-induced increase in hepatic glucose production in the postabsorptive state and during hyperinsulinemia.lipid; hepatic insulin resistance FREE FATTY ACIDS (FFA), which are often elevated in obese individuals (6, 15, 29,70), have been implicated as an important causative link in the associations between obesity, insulin resistance, and type 2 diabetes mellitus (11,48,56,73,82). Elevated plasma FFA clearly impair the ability of insulin to stimulate muscle glucose uptake (45,98). This effect is associated with a reduction in insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity, an important step in the insulin-signaling cascade that has been shown to be inhibited by FFA-induced PKC activation in muscle (42,53). In contrast, although a number of studies have indicated that elevated plasma FFA and high-fat diets can increase postabsorptive (referred to throughout this manuscript as "basal") hepatic glucose production (HGP) (7, 14,67,68,113) and induce hepatic insulin resistance (i.e., reduce the ability of insulin to suppress HGP) (9, 13,51,67,68,74,91,97,102,111,125), the magnitude of these effects and the mechanisms involved remain controversial.Because elevated HGP and hepatic insulin resistance have been well documented in individuals with type 2 diabetes (12, 40,85), studies that examine the effects of FFA on hepatic glucose metabolism are essential in understanding the pathogenesis of insulin resistance in type 2 diabetes. In this brief review, the physiological effects of FFA on hepatic glucose metabolism and the putative mechanisms of these effects will be discussed. FFA AND BASAL HGP FFA and GluconeogenesisGlucose is produced by glycogenolysis and gluconeogenesis in the liver. FFA increase hepatic gluconeogenesis both in vitro and in vivo (11, 20,127). FFA stimulation of gluconeogenesis has been attributed to the production of 1) acetyl-CoA derived from FFA oxidation, which allosterically activates pyruvate carboxylase, 2) NADH, which is used for the formation of glyceraldehyde 3-phosphate from 1,3-bisphosphoglycerate, and 3) ATP, which is used as an energy source. Additionally, increased levels of citrate (product of acetyl-CoA derived from FFA o...

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Section: Hepatic Glucokinase and Glucose-6-phosphatasementioning

confidence: 99%

Mechanisms of the free fatty acid-induced increase in hepatic glucose production

Lam

Carpentier

Lewis

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

236

149

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“…Additionally, higher GK activities than in the control group were reported in rats fed on a HF (25 % coconut oil) -high cholesterol (1 %) diet, which has been associated with the needs of the liver to synthesise other substrates when glucose provided by the diet is low (94) . In this sense, it is known that NEFA inhibit GK activity through allosteric binding (95) and impair GK translocation in hepatocytes (96) . The effect of fatty acids depends on their nature.…”

Section: Rattus Norvegicusmentioning

confidence: 99%

Nutritional regulation of glucokinase: a cross-species story

Panserat

Rideau²,

Polakof

2014

Nutr. Res. Rev.

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The glucokinase (GK) enzyme (EC 2.7.1.1.) is essential for the use of dietary glucose because it is the first enzyme to phosphorylate glucose in excess in different key tissues such as the pancreas and liver. The objective of the present review is not to fully describe the biochemical characteristics and the genetics of this enzyme but to detail its nutritional regulation in different vertebrates from fish to human. Indeed, the present review will describe the existence of the GK enzyme in different animal species that have naturally different levels of carbohydrate in their diets. Thus, some studies have been performed to analyse the nutritional regulation of the GK enzyme in humans and rodents (having high levels of dietary carbohydrates in their diets), in the chicken (moderate level of carbohydrates in its diet) and rainbow trout (no carbohydrate intake in its diet). All these data illustrate the nutritional importance of the GK enzyme irrespective of feeding habits, even in animals known to poorly use dietary carbohydrates (carnivorous species).

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“…Post-translationally, glucokinase is regulated by an interaction with glucokinase regulatory protein (GCKR), where binding to GCKR results in the loss of enzymatic activity and localization to the nucleus, while active glucokinase is found in the cytoplasm and is not bound to GCKR (Agius and Peak, 1997;van Schaftingen et al, 1997). Levels of fructose-6-phosphate, which change in parallel with blood glucose levels, regulate the binding of glucokinase with GCKR, allowing glucokinase to be active only when blood glucose levels are elevated (Agius and Peak, 1997;van Schaftingen et al, 1997).…”

Section: Glucokinase Regulatory Protein and The Tissue-specific Rolesmentioning

confidence: 99%

“…Levels of fructose-6-phosphate, which change in parallel with blood glucose levels, regulate the binding of glucokinase with GCKR, allowing glucokinase to be active only when blood glucose levels are elevated (Agius and Peak, 1997;van Schaftingen et al, 1997). GCKR is only abundantly expressed in the liver, and not appreciably in the other sites of glucokinase expression (Detheux et al, 1993;Vandercammen and Van Schaftingen, 1993).…”

Section: Glucokinase Regulatory Protein and The Tissue-specific Rolesmentioning

confidence: 99%

Evolution of glucose utilization: Glucokinase and glucokinase regulator protein

Irwin

2014

Molecular Phylogenetics and Evolution

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Glucose is an essential nutrient that must be distributed throughout the body to provide energy to sustain physiological functions. Glucose is delivered to distant tissues via be blood stream, and complex systems have evolved to maintain the levels of glucose within a narrow physiological range. Phosphorylation of glucose, by glucokinase, is an essential component of glucose homeostasis, both from the regulatory and metabolic point-of-view. Here we review the evolution of glucose utilization from the perspective of glucokinase. We discuss the origin of glucokinase, its evolution within the hexokinase gene family, and the evolution of its interacting regulatory partner, glucokinase regulatory protein (GCKR). Evolution of the structure and sequence of both glucokinase and GCKR have been necessary to optimize glucokinase in its role in glucose metabolism.

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Binding and translocation of glucokinase in hepatocytes

Cited by 22 publications

References 9 publications

Mechanisms of the free fatty acid-induced increase in hepatic glucose production

Mechanisms of the free fatty acid-induced increase in hepatic glucose production

Nutritional regulation of glucokinase: a cross-species story

Evolution of glucose utilization: Glucokinase and glucokinase regulator protein

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