Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose

Parniak, Michael A.; Kalant, N.

doi:10.1042/bj2510795

Cited by 20 publications

(13 citation statements)

References 32 publications

(44 reference statements)

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“…Well controlled studies need to be conducted in human subjects to determine the effect of long-term physiologic doses of fructose (incorporated into mixed meals) on tissue glycogen storage. It would also be interesting to know whether glucose and fructose act synergistically on glycogen synthesis in human tissue as they have been reported to do in rat liver (15,71,74,107,108).…”

Section: Effect Of Fructose On Glycogen Synthesismentioning

confidence: 93%

Current Issues in Fructose Metabolism

Henry¹,

Crapo²,

Thorburn³

1991

Annu. Rev. Nutr.

102

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The ingestion of fructose, particularly in refined form, has significantly increased in the North American diet over the last two decades. The unique way in which fructose is metabolized has given rise to much research examining whether fructose is advantageous in appetite control, exercise endurance, and disease states such as diabetes. Overall, there is very little evidence that modest amounts of fructose have detrimental effects on carbohydrate and lipid metabolism in nondiabetic or NIDDM subjects or that its use is particularly advantageous compared to that of other sugars. However, fructose can cause insulin and triglyceride levels to rise dramatically, and hence be potentially harmful, in a subgroup of NIDDM subjects who have concomitant pronounced hypertriglyceridemia. Large doses of fructose should also be avoided by subjects with gout because of the hyperuricemia which may result. No evidence exists that fructose has any clear advantages over glucose in regard to exercise endurance. Similarly there is no conclusive evidence that physiologic amounts of dietary fructose exacerbate copper deficiency or aid in weight control.

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Section: Effect Of Fructose On Glycogen Synthesismentioning

confidence: 93%

Current Issues in Fructose Metabolism

Henry¹,

Crapo²,

Thorburn³

1991

Annu. Rev. Nutr.

102

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“…After the incubation, the HCl was neutralized with an equal volume of 2 M NaOH, and the NaOH samples were neutralized with an equal volume of 2 M HCl. Glucose concentrations were measured with a glucose kit from Sigma, and the results were normalized by protein concentrations (27).…”

Section: Micementioning

confidence: 99%

Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance

Garbacz

Miller

et al. 2016

Molecular and Cellular Biology

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The common complications in obesity and type 2 diabetes include hepatic steatosis and disruption of glucose-glycogen homeostasis, leading to hyperglycemia. Fatty acid translocase (FAT/CD36), whose expression is inducible in obesity, is known for its function in fatty acid uptake. Previous work by us and others suggested that CD36 plays an important role in hepatic lipid homeostasis, but the results have been conflicting and the mechanisms were not well understood. In this study, by using CD36-overexpressing transgenic (CD36Tg) mice, we uncovered a surprising function of CD36 in regulating glycogen homeostasis. Overexpression of CD36 promoted glycogen synthesis, and as a result, CD36Tg mice were protected from fasting hypoglycemia. When challenged with a high-fat diet (HFD), CD36Tg mice showed unexpected attenuation of hepatic steatosis, increased very low-density lipoprotein (VLDL) secretion, and improved glucose tolerance and insulin sensitivity. The HFD-fed CD36Tg mice also showed decreased levels of proinflammatory hepatic prostaglandins and 20-hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictive and proinflammatory arachidonic acid metabolite. We propose that CD36 functions as a protective metabolic sensor in the liver under lipid overload and metabolic stress. CD36 may be explored as a valuable therapeutic target for the management of metabolic syndrome. Individuals with metabolic syndrome or type 2 diabetes are susceptible to nonalcoholic fatty liver disease (1) and disruption of hepatic glucose and glycogen homeostasis (2). Hepatic steatosis is defined as an excess accumulation of fat in hepatocytes. Previous reports suggested that fatty acid translocase (FAT/CD36) plays an important role in hepatic lipid homeostasis (3-6). CD36 is a multiligand class B scavenger receptor with high affinity for lipids and lipid-containing ligands. CD36 is known for its lipid uptake function in macrophages, skeletal muscle, and the heart. However, the role of CD36 in hepatic lipid metabolism is still not well understood, and the available evidence is often conflicting, partly due to the lack of a reliable in vivo liver-specific gain-of-function model to specifically evaluate the function of CD36 in the liver.The basal expression of CD36 in the liver is low; however, it is highly inducible by a high-fat diet (HFD) (3). The hepatic expression of CD36 is under the transcriptional control of the nuclear receptors: liver X receptor (LXR), pregnane X receptor (PXR), peroxisome proliferator-activated receptors (PPARs), and the aryl hydrocarbon receptor (AhR) (4). Some studies have suggested that hepatic CD36, by functioning as a fatty acid transporter, has a role in the pathogenesis of hepatic steatosis (3), obesity (7, 8), and age-related hepatic steatosis (5). Furthermore, we and others reported that induction of CD36 was a common factor in fatty liver following the activation of LXR and PXR (6, 9). On the other hand, recent reports suggested that CD36 signaling might actually be beneficial in preventing fatty live...

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“…It has been proposed that this effect results from a decrease in the breakdown of newly deposited glycogen [31,321, owing to inhibition of glycogen phosphorylase by millimolar concentrations of F r u l P [31,331. However, at the concentrations found in the portal blood after a fructose-rich meal (z 2 mM), the ketose also stimulates the incorporation of ['4C]glucose into COz, lactate, pyruvate and amino acids in isolated hepatocytes [9] and increases the glucose uptake by the perfused liver [34].…”

Section: Physiological Implicationsmentioning

confidence: 99%

Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes

Schaftingen

Vandercammen

1989

European Journal of Biochemistry

107

103

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The phosphorylation of glucose was measured by the formation of [3H]Hz0 from [2-3H]glucose in suspensions of freshly isolated rat hepatocytes. Fructose (0.2 mM) stimulated 2 -4-fold the rate of phosphorylation of 5 mM glucose although not of 40 mM glucose, thus increasing the apparent affinity of the glucose phosphorylating system. A half-maximal stimulatory effect was observed at about 50 pM fructose. Stimulation was maximal 5 niin after addition of the ketose and was stable for at least 40 min, during which period 60% of the fructose was consumed. The effect of fructose was reversible upon removal of the ketose. Sorbitol and tagatose were as potent as fructose in stimulating the phosphorylation of 5 mM glucose. D-Glyceraldehyde also had a stimulatory effect but at tenfold higher concentrations. In contrast, dihydroxyacetone had no significant effect and glycerol inhibited the detritiation of glucose. Oleate did not affect the phosphorylation of glucose, even in the presence of fructose, although it stimulated the formation of ketone bodies severalfold, indicating that it was converted to its acylCoA derivative. These results allow the conclusion that fructose stimulates glucokinase in the intact hepatocyte. They also suggest that this effect is mediated through the formation of fructose I-phosphate, which presumably interacts with a competitive inhibitor of glucokinase other than long-chain acyl-CoAs.Glucokinase (hexokinase D) is a high K , hexokinase present in two glucose-sensitive cell types, the liver parenchymal cell and the pancreatic b-cell [l, 21. The activity of this enzyme is regulated in vivo by the intracellular concentration of glucose, which is permanently adjusted to the level of the glycemia in both cell types [3, 41. Kinetic studies have shown that unlike other hexokinases, glucokinase is not inhibited by physiological concentrations of Glc6P 111. Furthermore, although purified glucokinase has been shown to be inhibited by long-chain Fatty acyl-CoAs [5 -71, the physiological significance of this effect has not been demonstrated. Control by substrate concentration represents, therefore, the only type of short-term regulation that is currently considered to play a role under physiological conditions. The literature contains, however, some indications that the activity of glucokinase can be regulated rapidly by other means. Glucose phosphorylation, as measured by the loss of tritium from [2-3H]glucose [8], increases in isolated hepatocytes in response to the addition of 2.5 mM fructose [9] or to the presence of a potassium-rich medium [lo].The purpose of our work was to elucidate the mechanism of the fructose effect. This paper reports studies in which glucose phosphorylation was measured on freshly isolated hepatocytes by the [2-3H]glucose technique and from which we draw the tentative conclusion that the effect of fructose is mediated by Frul P. The accompanying paper [I I] describes the existence in liver of a protein that inhibits glucokinase and whose effect is strengthened by Fru6P and anta...

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Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose

Cited by 20 publications

References 32 publications

Current Issues in Fructose Metabolism

Current Issues in Fructose Metabolism

Hepatic Overexpression of CD36 Improves Glycogen Homeostasis and Attenuates High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance

Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes

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