Sleep-associated fall in glucose disposal and hepatic glucose output in normal humans. Putative signaling mechanism linking peripheral and hepatic events

Clore, J. N.; Nestler, J. E.; Blackard, W. G.

doi:10.2337/diabetes.38.3.285

Cited by 28 publications

(26 citation statements)

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“…It is suggested that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein. Taken together with numerous other reports on the impact of lipids on carbohydrate metabolism in skeletal muscle (7)(8)(9), liver (8)(9)(10)12,13), and pancreatic (3-cells (11,38,39), our finding provides experimental support for the role of hyperlipidemia in the pathogenesis of NIDDM (40,41).…”

Section: Discussionsupporting

confidence: 50%

“…It also suggests that the mechanism(s) by which a sustained increase in the availability of lipids might affect hepatic glucose output involves more than the short-term increase in the rate of gluconeogenesis (15). Indeed, increased hepatic glucose production is an early (~1 week) consequence of high-fat feeding in rodents (34), and the plasma FFA levels are closely related to the rate of endogenous glucose production in humans (8)(9)(10)12,13). Furthermore, most patients with NIDDM display increased concentrations of plasma FFA throughout the day (14).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, numerous studies have shown that the rate of endogenous glucose production is closely related to the circulating plasma FFA concentrations ER, endoplasmic reticulum; FFA, free fatty acid; PMSF, phenylmethylsulfonyl fluoride; SSC, sodium chloride-sodium citrate. (9,10,12,13) and that the majority of individuals with NIDDM have increased 24-h plasma FFA profiles (14). While the acute effects of an increase in plasma FFA availability are likely to be largely caused by its known stimulatory effect on gluconeogenesis (15), much less is known regarding the long-term consequences of increased hepatic availability of FFAs.…”

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confidence: 99%

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Induction of Hepatic Glucose-6-Phosphatase Gene Expression by Lipid Infusion

et al. 1997

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The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) complex. The recently cloned catalytic unit of this complex has been shown to be regulated by insulin, dexamethasone, cAMP, and glucose. Using a combination of intralipid and/or nicotinic acid infusions and a pancreatic clamp technique, we maintained plasma free fatty acids (FFAs) at three different levels (0.26 ± 0.07, 0.56 ± 0.09, and 1.59 ± 0.12 mmol/1) in the presence of well-controlled hormonal and metabolic conditions. An increase in the plasma FFA concentration within the physiological range caused a rapid, greater than threefold increase in the mRNA and protein levels of the catalytic subunit of Glc-6-Pase in the liver. These data indicate that the in vivo gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein. G lucose-6-phosphatase (Glc-6-Pase) catalyzes the final enzymatic step for hepatic gluconeogenesis and glycogenolysis (1). Glc-6-Pase is a complex of proteins with the catalytic portion deeply embedded in the endoplasmic reticulum (ER) (1). Because of its intracellular localization, it has long been suggested that the lipid composition of the ER membrane would play a pivotal role in the regulation of Glc-6-Pase activity. Indeed, some recent reports have shown an acute inhibitory effect of fatty acyl-CoA (2,3) and fatty acid ester (4,5) on Glc-6-Pase activity. In contrast, increased hepatic Glc-6-Pase activity has been reported to follow prolonged increases in dietary saturated fatty acids (6).Important interactions between glucose and lipid metabolism have been demonstrated in skeletal muscle (7-9), liver (8-10), and 3-cells (11). In particular, numerous studies have shown that the rate of endogenous glucose production is closely related to the circulating plasma FFA concentrations ER, endoplasmic reticulum; FFA, free fatty acid; PMSF, phenylmethylsulfonyl fluoride; SSC, sodium chloride-sodium citrate. (9,10,12,13) and that the majority of individuals with NIDDM have increased 24-h plasma FFA profiles (14). While the acute effects of an increase in plasma FFA availability are likely to be largely caused by its known stimulatory effect on gluconeogenesis (15), much less is known regarding the long-term consequences of increased hepatic availability of FFAs.Indeed, dietary fatty acids have been shown to regulate the gene expression of pancreatic GLUT2 and glucokinase (16), and long-chain fatty acids can induce the expression of the genes for the adipocyte fatty acid-binding protein aP2 (17) and liver carnitine palmitoyltransferase I (CPT I) (18). Additionally, the expression of a number of hepatic lipogenic, glycolytic, and gluconeogenic genes is regulated by polyunsaturated fatty acids at the transcriptional level (19,20).Since Glc-6-Pase mRNA and activity increase in metabolic conditions associated with high ...

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Induction of Hepatic Glucose-6-Phosphatase Gene Expression by Lipid Infusion

et al. 1997

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“…For example, Clore et al demonstrated a fall in both FFA and HGO during sleep (34), and that preventing the fall in FFA with heparin increased gluconeogenesis without any change in HGO (35). These results led the authors to hypothesize that the relative contributions of gluconeogenesis and glycogenolysis are autoregulated; that is, that decreases in gluconeogenesis are compensated for by increases in glycogenolysis.…”

Section: Discussionmentioning

confidence: 91%

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

Rebrin¹,

Steil²,

Mittelman³

et al. 1996

J. Clin. Invest.

267

186

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Suppression of hepatic glucose output (HGO) has been shown to be primarily mediated by peripheral rather than portal insulin concentrations; however, the mechanism by which peripheral insulin suppresses HGO has not yet been determined. Previous findings by our group indicated a strong correlation between free fatty acids (FFA) and HGO, suggesting that insulin suppression of HGO is mediated via suppression of lipolysis. To directly test the hypothesis that insulin suppression of HGO is causally linked to the suppression of adipose tissue lipolysis, we performed euglycemic-hyperinsulinemic glucose clamps in conscious dogs ( n ϭ 8) in which FFA were either allowed to fall or were prevented from falling with Liposyn plus heparin infusion (LI; 0.

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“…Previous studies have demonstrated that the plasma concentrations of growth hormone [30] ACTH [31] and prolactin [32] show a diurnal periodicity in which higher plasma concentrations are observed during the night as compared to the daytime. In addition, plasma concentrations of free fatty acids are known to rise at night in response to an increased rate of lipolysis [33]. Plasma concentrations of insulin are also known to be suppressed during periods of fasting as occur during the nocturnal hours in normal human subjects.…”

Section: Discussionmentioning

confidence: 99%

Diurnal variations in the plasma concentrations of mevalonic acid in patients with abetalipoproteinaemia

Pappu

Illingworth

1994

Eur J Clin Investigation

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Abstract. Previous studies have demonstrated that changes in the rates of cholesterol biosynthesis can be evaluated by the determination of plasma concentrations of sterol intermediates, including mevalonic acid and lathosterol and that, in normal human subjects, a diurnal rhythm exists in which the highest concentrations of sterol intermediates are observed at night. The factors responsible for this diurnal rhythm in cholesterol synthesis are, however, unknown. To test the hypothesis that the nocturnal increase in cholesterol biosynthesis is attributable to a reduced rate of hepatic uptake of chylomicron remnants at night as compared to higher rates of uptake during the daytime in response to alimentary lipaemia, we have examined the diurnal rhythm of mevalonic acid in six normal volunteers and three patients with phenotypic abetalipoproteinaemia. The latter patients do not absorb appreciable amounts of dietary cholesterol and are unable to synthesize chylomicron particles. Plasma concentrations of mevalonic acid exhibited a diurnal rhythm in the normal subjects, and the highest plasma concentrations were observed between 24.00 hours/04.00 hours. A similar rhythm was observed in the plasma of patients with abetalipoproteinaemia. These results suggest that the nocturnal increase in cholesterol biosynthesis which occurs in humans is not attributable to reduced hepatic uptake of chylomicron remnants at night; further studies are needed to better define those factors which influence the periodicity of cholesterol biosynthesis in humans.

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Sleep-associated fall in glucose disposal and hepatic glucose output in normal humans. Putative signaling mechanism linking peripheral and hepatic events

Cited by 28 publications

References 0 publications

Induction of Hepatic Glucose-6-Phosphatase Gene Expression by Lipid Infusion

Induction of Hepatic Glucose-6-Phosphatase Gene Expression by Lipid Infusion

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

Diurnal variations in the plasma concentrations of mevalonic acid in patients with abetalipoproteinaemia

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