Compartmentation of glucose 6-phosphate in hepatocytes

Kalant, N.; Parniak, Michael A.; Lemieux, Melissa

doi:10.1042/bj2480927

Cited by 28 publications

(19 citation statements)

References 22 publications

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“…Although the in vivo administration of the gluconeogenic precursors did not affect the concentration of plasma mannose, mannose output was decreased when isolated livers were perfused using lactate; this inconsistency is probably due to lack of neural and endocrine control in the perfusion experiment. It is believed that glucose 6-phosphate in hepatocytes does not exist as a homogeneous pool but is associated with separate compartments linked to glycogenolysis, gluconeogenesis, and glycolysis (4,11). This may explain why mannose production is increased when glycogenolysis, but not gluconeogenesis, is enhanced.…”

Section: Discussionmentioning

confidence: 97%

Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

Taguchi¹,

Yamashita²,

Mizutani³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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D-mannose is an essential monosaccharide constituent of glycoproteins and glycolipids. However, it is unknown how plasma mannose is supplied. The aim of this study was to explore the source of plasma mannose. Oral administration of glucose resulted in a significant decrease of plasma mannose concentration after 20 min in fasted normal rats. However, in fasted type 2 diabetes model rats, plasma mannose concentrations that were higher compared with normal rats did not change after the administration of glucose. When insulin was administered intravenously to fed rats, it took longer for plasma mannose concentrations to decrease significantly in diabetic rats than in normal rats (20 and 5 min, respectively). Intravenous administration of epinephrine to fed normal rats increased the plasma mannose concentration, but this effect was negated by fasting or by administration of a glycogen phosphorylase inhibitor. Epinephrine increased mannose output from the perfused liver of fed rats, but this effect was negated in the presence of a glucose-6-phosphatase inhibitor. Epinephrine also increased the hepatic levels of hexose 6-phosphates, including mannose 6-phosphate. When either lactate alone or lactate plus alanine were administered as gluconeogenic substrates to fasted rats, the concentration of plasma mannose did not increase. When lactate was used to perfuse the liver of fasted rats, a decrease, rather than an increase, in mannose output was observed. These findings indicate that hepatic glycogen is a source of plasma mannose.

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Section: Discussionmentioning

confidence: 97%

Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

Taguchi¹,

Yamashita²,

Mizutani³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…This implies that certain molecules of glucose 6-phosphate are destined for glycolysis and that when this is depressed the fate of these molecules is immediate dephosphorylation. It is difficult to explain this phenomenon without invoking the concept that the glucose 6-phosphate pool is not homogenous [35,36] but is segregated into glycolytic and glycogenic moieties. Even if this were to be the case, it does not explain by what mechanism glucose 6-phosphate surplus to glycolysis is detected and channelled towards de-phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes

et al. 1993

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We have studied the inhibitory action of long-and short-chain fatty acids on hepatic glucose utilization in hepatocytes isolated from fasted rats. The rates of hepatic glucose phosphorylation and glycolysis were determined from the tritiated products of [2-'H] and [6-3H]glucose metabolism, respectively. The difference between these was taken as an estimate of the 'cycling' between glucose and glucose-6-phosphate. In the presence of 40 mM glucose this cycling was estimated at 0.68 pmol/min/g wet wt. Glucose phosphorylation was unaffected during palmitate and hexanoate oxidation to ketone bodies but glycolysis was inhibited. The rate of glucose cycling was increased during this phase to 1.25 pmol/min/g. Following the complete metabolism of the fatty acids, glycolysis was reinstated and cycling rates returned to control levels. Hepatic glucose cycling appears to be an important component of the glucose/fatty acid cycle.

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“…Gustafson et al (33) also noted that enhancement of hepatocyte G6P levels by inhibition of G6P translocase did not stimulate glucose synthase activity in either the presence or absence of oleate. Thus, changes in hepatic G6P do not always result in changes in glycogen synthase activity, a phenomenon that might be related to the metabolic zonation of the liver (42) or to compartmentation of G6P within the hepatocyte (43,44). Net hepatic glycogen synthesis is the sum of the processes of glycogen synthesis and glycogenolysis.…”

Section: Discussionmentioning

confidence: 99%

Nonesterified Fatty Acids and Hepatic Glucose Metabolism in the Conscious Dog

et al. 2004

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We used tracer and arteriovenous difference techniques in conscious dogs to determine the effect of nonesterified fatty acids (NEFAs) on net hepatic glucose uptake (NHGU E levated levels of nonesterified fatty acids (NEFAs) impair insulin-mediated suppression of endogenous glucose production under postabsorptive conditions (1-9). However, the relationship between NEFA concentrations and net splanchnic or hepatic glucose uptake (HGU) in the postprandial state is less clearly understood. NEFA concentrations and net hepatic or splanchnic uptake of NEFA fall during the postprandial period (10 -12). Postprandial NEFA concentrations are higher in individuals with type 2 diabetes than nondiabetic individuals, even though their insulin concentrations are also higher (13,14). Normally, the liver extracts approximately one-third of a glucose load delivered enterally or into the portal vein (15-17), but net HGU (NHGU) is reduced in individuals with type 2 diabetes (13,18) and in those at risk of developing type 2 diabetes (19,20). Whether an elevation of NEFA concentrations might contribute to impaired postprandial HGU has not been established.We hypothesized that the failure to suppress NEFA concentrations postprandially would reduce NHGU. To test this hypothesis, we studied conscious dogs under euinsulinemic-hyperglycemic conditions as a first step toward understanding the impact of elevated NEFA concentrations in conjunction with the relative insulin deficiency of type 2 diabetes. RESEARCH DESIGN AND METHODSStudies were carried out on conscious mongrel dogs of both sexes, fasted 42 h, and with a mean weight of 23.6 Ϯ 0.9 kg. The 42-h fast was chosen because it is a time when hepatic glycogen has reached a stable minimum in both dogs and humans (21,22). Approximately 16 days before study, each dog underwent a laparotomy for placement of ultrasonic flow probes (Transonic Systems, Ithaca, NY) around the portal vein and the hepatic artery, as well as insertion of sampling catheters into the left common hepatic vein, the portal vein, and a femoral artery, and the insertion of infusion catheters into a splenic and a jejunal vein (9). Diet, housing, protocol approval, criteria for study, and preparation for study were as previously described (15).Each experiment consisted of a 90-min equilibration period (Ϫ120 to Ϫ30 min), a 30-min basal period (Ϫ30 to 0 min), and a 240-min experimental period (0 -240 min). At Ϫ120 min, priming doses of [U-14 C]glucose (11 Ci/kg) and [3-3 H]glucose (34 Ci/kg) were given, and constant infusions of [U-14 C]glucose (0.4 Ci/min), [3-3 H]glucose (0.35 Ci/min), and indocyanine green dye (0.14 mg/min) (Sigma, St. Louis, MO) were initiated. A constant peripheral infusion of p-aminohippuric acid (PAH) (1.7 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) (Sigma) was also started at Ϫ120 min, continuing until 0 min. At 0 min, a constant peripheral infusion of somatostatin (0.8 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) (Bachem, Torrance, CA) was begun to suppress endogenous insulin and glucagon secretion, and porcine insulin (0.4 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ...

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Compartmentation of glucose 6-phosphate in hepatocytes

Cited by 28 publications

References 22 publications

Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes

Nonesterified Fatty Acids and Hepatic Glucose Metabolism in the Conscious Dog

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