Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

2007 ◽  
Vol 292 (4) ◽  
pp. R1400-R1407 ◽  
Author(s):  
Dalila Azzout-Marniche ◽  
Claire Gaudichon ◽  
Clémence Blouet ◽  
Cécile Bos ◽  
Véronique Mathé ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Amino Acid ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthesis ◽  
High Protein ◽  
Hepatic Glycogen ◽  
Molecular Evidence ◽  
Experimental Conditions ◽  
Fed State

This paper provides molecular evidence for a liver glyconeogenic pathway, that is, a concomitant activation of hepatic gluconeogenesis and glycogenesis, which could participate in the mechanisms that cope with amino acid excess in high-protein (HP) fed rats. This evidence is based on the concomitant upregulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression, downregulation of glucose 6-phosphatase catalytic subunit (G6PC1) gene expression, an absence of glucose release from isolated hepatocytes and restored hepatic glycogen stores in the fed state in HP fed rats. These effects are mainly due to the ability of high physiological concentrations of portal blood amino acids to counteract glucagon-induced liver G6PC1 but not PEPCK gene expression. These results agree with the idea that the metabolic pathway involved in glycogen synthesis is dependent upon the pattern of nutrient availability. This nonoxidative glyconeogenic disposal pathway of gluconeogenic substrates copes with amino excess and participates in adjusting both amino acid and glucose homeostasis. In addition, the pattern of PEPCK and G6PC1 gene expression provides evidence that neither the kidney nor the small intestine participated in gluconeogenic glucose production under our experimental conditions. Moreover, the main glucose-6-phosphatase (G6Pase) isoform expressed in the small intestine is the ubiquitous isoform of G6Pase (G6PC3) rather than the G6PC1 isoform expressed in gluconeogenic organs.

Differential effect of amino acid infusion route on net hepatic glucose uptake in the dog

1999 ◽  
Vol 276 (2) ◽  
pp. E295-E302 ◽  
Author(s):  
Mary Courtney Moore ◽  
Po-Shiuan Hsieh ◽  
Paul J. Flakoll ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Amino Acid ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Portal Infusion

Concomitant portal infusion of gluconeogenic amino acids (GNGAA) and glucose significantly reduces net hepatic glucose uptake (NHGU), in comparison with NHGU during portal infusion of glucose alone. To determine whether this effect on NHGU is specific to the portal route of GNGAA delivery, somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and intraportal glucose (to increase the hepatic glucose load by ∼50%) were infused for 240 min. GNGAA were infused peripherally into a group of dogs (PeAA), at a rate to match the hepatic GNGAA load in a group of dogs that were given the same GNGAA mixture intraportally (PoAA) at 7.6 μmol ⋅ kg−1 ⋅ min−1(9). The arterial blood glucose concentrations and hepatic glucose loads were the same in the two groups, but NHGU (−0.9 ± 0.2 PoAA and −2.1 ± 0.5 mg ⋅ kg−1 ⋅ min−1in PeAA, P < 0.05) and net hepatic fractional extraction of glucose (2.6 ± 0.7% in PoAA vs. 5.9 ± 1.4% in PeAA, P < 0.05) differed. Neither the hepatic loads nor the net hepatic uptakes of GNGAA were significantly different in the two groups. Net hepatic glycogen synthesis was ∼2.5-fold greater in PeAA than PoAA ( P < 0.05). Intraportal, but not peripheral, amino acid infusion suppresses NHGU and net hepatic glycogen synthesis in response to intraportal glucose infusion.

scholarly journals Amylin impairment of insulin effects on glycogen synthesis and phosphoenolpyruvate carboxykinase gene expression in rat primary cultured hepatocytes

1994 ◽  
Vol 304 (2) ◽  
pp. 449-453 ◽  
Author(s):  
S Baqué ◽  
J J Guinovart ◽  
A M Gómez-Foix
Keyword(s):  
Gene Expression ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Mrna Level ◽  
Rat Hepatocytes ◽  
Synthesis Rate ◽  
Cultured Hepatocytes ◽  
Glycogen Accumulation ◽  
Primary Cultured Hepatocytes

The ability of amylin to impair hepatic insulin action is controversial. We have found that the effect of amylin in primary cultured hepatocytes is strongly dependent on the culture conditions. Only in hepatocytes preincubated in the presence of fetal serum did amylin, at concentrations ranging from 1 to 100 nM, reduce insulin-stimulated glycogen synthesis rate and glycogen accumulation without showing direct effects. Neither basal glycogen synthase nor glycogen phosphorylase activity was modified by amylin treatment. Nevertheless, amylin (100 nM) blocked the activation of glycogen synthase by insulin. Amylin also proved capable of opposing the reduction in the expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene induced by insulin, whereas the basal mRNA level of PEPCK was unaffected by amylin treatment. Thus, these results show that, in cultured rat hepatocytes, amylin is indeed able to interfere with insulin regulation of glycogenesis and PEPCK gene expression, favouring the hypothesis that amylin may modulate liver sensitivity to insulin.

Molecular morphology of hepatic glycogen metabolism

1991 ◽  
Vol 49 ◽  
pp. 48-49
Author(s):  
Robert R. Cardell
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Smooth Endoplasmic Reticulum ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Hepatic Glycogen ◽  
Hepatic Gluconeogenesis ◽  
Morphological Aspects ◽  
Molecular Morphology

For over two decades we have studied morphological aspects of hepatic glycogen metabolism, particularly the role of smooth endoplasmic reticulum in this process. Recently investigators have emphasized the role of hepatic gluconeogenesis (formation of glucose from non-carbohydrate precursors) in glycogen synthesis. To contribute new morphological information to this discussion we have developed probes for the detection of the relevant gluconeogenic enzymes by immunocytochemistry and the expression of the genes for the enzymes by in situ hybridization histochemistry. In this report we present: our work on the expression of a gene for the major rate limiting enzyme in hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK).

Glucose homeostasis in a carnivorous animal (cat) and in rats fed a high-protein diet

1980 ◽  
Vol 239 (5) ◽  
pp. R437-R444 ◽  
Author(s):  
I. C. Kettelhut ◽  
M. C. Foss ◽  
R. H. Migliorini
Keyword(s):  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
High Protein Diet ◽  
Liver Glycogen ◽  
High Protein ◽  
Glucose Turnover ◽  
Fed State ◽  
Liver Cytosol ◽  
Reduced Body ◽  
Efficient Reduction

Glucose homeostasis in a carnivorous (cat) and in an omnivorous (rat) animal fed a high-protein, low-carbohydrate (HP) diet followed a pattern similar to that previously found in carnivorous birds [Am. J. Physiol. 234 (Regulatory Integrative Comp. Physiol. 3): R115-R121, 1978]. Thus, compared to controls given carbohydrate-rich (HC) diets. HP-fed animals had, in the fed state, lower levels of blood sugar, lower concentrations of liver glycogen, and a tendency to reduced body glucose mass. During fasting, their liver glycogen was little mobilized and their glycemia remained remarkably constant. Accordingly, their body glucose mass remained unchanged. Gluconeogenic capacity, already high in the fed state, was not further activated by fasting. Phosphoenolpyruvate carboxykinase activity actually decreased in rat liver cytosol, remaining unchanged in cat liver cytosol and mitochondria. [3H]glucose turnover studies revealed that in HP-fed cats and rats glucose replacement rates in the fed state were as high as in HC-fed animals and that the resistance of their glycemia to fasting depended on the high gluconeogenic capacity and not on a more efficient reduction of glucose utilization.

Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis

2007 ◽  
Vol 292 (6) ◽  
pp. E1683-E1693 ◽  
Author(s):  
Masako Doi ◽  
Ippei Yamaoka ◽  
Mitsuo Nakayama ◽  
Kunio Sugahara ◽  
Fumiaki Yoshizawa
Keyword(s):  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Synthesis ◽  
Isolated Hepatocytes ◽  
Hypoglycemic Effect ◽  
Whole Body ◽  
Hepatic Glycogen ◽  
Mrna Levels

Isoleucine, a branched chain amino acid, plays an important role in the improvement of glucose metabolism as evidenced by the increase of insulin-independent glucose uptake in vitro. This study evaluated the effect of isoleucine on glucose uptake and oxidation in fasted rats and on gluconeogenesis in vivo and in vitro. Oral administration of isoleucine decreased the plasma glucose level by 20% and significantly increased muscle glucose uptake by 71% without significant elevation of the plasma insulin level compared with controls at 60 min after administration. Furthermore, expiratory excretion of 14CO2 from [U-14C]glucose in isoleucine-administered rats was increased by 19% compared with controls. Meanwhile, isoleucine decreased AMP levels in the liver but did not affect hepatic glycogen synthesis. Under insulin-free conditions, isoleucine significantly inhibited glucose production when alanine was used as a glucogenic substrate in isolated hepatocytes. This inhibition by isoleucine was also associated with a decline in mRNA levels for phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (G6Pase) and a decreased activity of G6Pase in isolated hepatocytes. These findings suggest that a reduction of gluconeogenesis in liver, along with an increase of glucose uptake in the muscle, is also involved in the hypoglycemic effect of isoleucine. In conclusion, isoleucine administration stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to the hypoglycemic effect in rats.

Hepatic glucose disposition during concomitant portal glucose and amino acid infusions in the dog

1998 ◽  
Vol 274 (5) ◽  
pp. E893-E902 ◽  
Author(s):  
Mary Courtney Moore ◽  
Paul J. Flakoll ◽  
Po-Shiuan Hsieh ◽  
Michael J. Pagliassotti ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Amino Acid ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Experimental Period ◽  
Hepatic Glycogen ◽  
Blood Concentrations ◽  
Amino Acid Infusion ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

The effect of concomitant intraportal infusion of glucose and gluconeogenic amino acids (AA) on net hepatic glucose uptake (NHGU) and glycogen synthesis was examined in 42-h-fasted dogs. After a basal period, there was a 240-min experimental period during which somatostatin was infused continuously into a peripheral vein and insulin and glucagon (at 3-fold basal and basal rates, respectively) and glucose (18.3 μmol ⋅ kg−1⋅ min−1) were infused intraportally. One group (PoAA, n = 7) received an AA mixture intraportally at 7.6 μmol ⋅ kg−1⋅ min−1, whereas the other group (NoAA, n = 6) did not receive AA. Arterial blood glucose concentrations and hepatic glucose loads were the same in the two groups. NHGU averaged 4.8 ± 2.0 (PoAA) and 9.4 ± 2.0 (NoAA) μmol ⋅ kg−1⋅ min−1( P < 0.05), and tracer-determined hepatic glucose uptake was 4.6 ± 1.6 (PoAA) and 10.0 ± 1.7 (NoAA) μmol ⋅ kg−1⋅ min−1( P < 0.05). AA data for PoAA and NoAA, respectively, were as follows: arterial blood concentrations, 1,578 ± 133 vs. 1,147 ± 86 μM ( P < 0.01); hepatic loads, 56 ± 3 vs. 32 ± 4 μmol ⋅ kg−1⋅ min−1( P < 0.01); and net hepatic uptakes, 14.1 ± 1.4 vs. 5.6 ± 0.4 μmol ⋅ kg−1⋅ min−1( P < 0.01). The rate of net hepatic glycogen synthesis was 7.5 ± 1.9 (PoAA) vs. 10.7 ± 2.3 (NoAA) μmol ⋅ kg−1⋅ min−1( P = 0.1). In a net sense, intraportal gluconeogenic amino acid delivery directed glucose carbon away from the liver. Despite this, net hepatic carbon uptake was equivalent in the presence and absence of amino acid infusion.

Drumstick is a zinc finger protein that antagonizes Lines to control patterning and morphogenesis of theDrosophilahindgut

Development ◽  
2002 ◽  
Vol 129 (15) ◽  
pp. 3645-3656 ◽  
Author(s):  
Ryan B. Green ◽  
Victor Hatini ◽  
Katherine A. Johansen ◽  
Xue-Jun Liu ◽  
Judith A. Lengyel
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Amino Acid ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Ectopic Expression ◽  
Genetic Data ◽  
Specific Pattern ◽  
Cell Rearrangement ◽  
Finger Protein

Elongation of the Drosophila embryonic hindgut epithelium occurs by a process of oriented cell rearrangement requiring the genes drumstick (drm) and lines (lin). The elongating hindgut becomes subdivided into domains – small intestine, large intestine and rectum – each characterized by a specific pattern of gene expression dependent upon normal drm and lin function. We show that drm encodes an 81 amino acid (10 kDa) zinc finger protein that is a member of the Odd-skipped family. drm expression is localized to the developing midgut-hindgut junction and is required to establish the small intestine, while lin is broadly expressed throughout the gut primordium and represses small intestine fate. lin is epistatic to drm, suggesting a model in which localized expression of drm blocks lin activity, thereby allowing small intestine fate to be established. Further supporting this model, ectopic expression of Drm throughout the hindgut produces a lin phenotype. Biochemical and genetic data indicate that the first conserved zinc finger of Drm is essential for its function. We have thus defined a pathway in which a spatially localized zinc finger protein antagonizes a globally expressed protein, thereby leading to specification of a domain (the small intestine) necessary for oriented cell rearrangement.

scholarly journals Cytosolic phosphoenolpyruvate carboxykinase as a cataplerotic pathway in the small intestine

2018 ◽  
Vol 315 (2) ◽  
pp. G249-G258 ◽  
Author(s):  
Austin Potts ◽  
Aki Uchida ◽  
Stanislaw Deja ◽  
Eric D. Berglund ◽  
Blanka Kucejova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Small Intestine ◽  
Fatty Acid ◽  
Amino Acid ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Postprandial Triglyceride ◽  
Amino Acid Profiles ◽  
Gluconeogenic Enzyme ◽  
Acid Esterification ◽  
Fatty Acid Esterification

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is a gluconeogenic enzyme that is highly expressed in the liver and kidney but is also expressed at lower levels in a variety of other tissues where it may play adjunct roles in fatty acid esterification, amino acid metabolism, and/or TCA cycle function. PEPCK is expressed in the enterocytes of the small intestine, but it is unclear whether it supports a gluconeogenic rate sufficient to affect glucose homeostasis. To examine potential roles of intestinal PEPCK, we generated an intestinal PEPCK knockout mouse. Deletion of intestinal PEPCK ablated ex vivo gluconeogenesis but did not significantly affect glycemia in chow, high-fat diet, or streptozotocin-treated mice. In contrast, postprandial triglyceride secretion from the intestine was attenuated in vivo, consistent with a role in fatty acid esterification. Intestinal amino acid profiles and 13C tracer appearance into these pools were significantly altered, indicating abnormal amino acid trafficking through the enterocyte. The data suggest that the predominant role of PEPCK in the small intestine of mice is not gluconeogenesis but rather to support nutrient processing, particularly with regard to lipids and amino acids. NEW & NOTEWORTHY The small intestine expresses gluconeogenic enzymes for unknown reasons. In addition to glucose synthesis, the nascent steps of this pathway can be used to support amino acid and lipid metabolisms. When phosphoenolpyruvate carboxykinase, an essential gluconeogenic enzyme, is knocked out of the small intestine of mice, glycemia is unaffected, but mice inefficiently absorb dietary lipid, have abnormal amino acid profiles, and inefficiently catabolize glutamine. Therefore, the initial steps of intestinal gluconeogenesis are used for processing dietary triglycerides and metabolizing amino acids but are not essential for maintaining blood glucose levels.

scholarly journals Metabolic effects of cortisol treatment in a marine teleost, the sea raven

1996 ◽  
Vol 199 (7) ◽  
pp. 1509-1514
Author(s):  
M M Vijayan ◽  
T P Mommsen ◽  
H C Glémet ◽  
T W Moon
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Coconut Oil ◽  
Glucose Production ◽  
Tyrosine Aminotransferase ◽  
Metabolic Effects ◽  
Hepatic Glycogen ◽  
Sea Raven ◽  
Hemitripterus Americanus

Sea raven (Hemitripterus americanus) given intraperitoneal implants of coconut oil containing cortisol (50 mg kg-1) and sampled 5 days later had plasma cortisol, glucose and urea concentrations higher than in a sham-implanted group. No differences in plasma ammonia, free amino acid or fatty acid concentrations were apparent between the cortisol- and sham-treated groups. There was no change in hepatic glycogen content, whereas glutamine synthetase, allantoicase, arginase, aspartate aminotransferase, tyrosine aminotransferase, alanine aminotransferase, glutamate dehydrogenase, phosphoenolpyruvate carboxykinase and 3-hydroxyacyl-coenzyme A dehydrogenase activities were higher in the cortisol-treated fish liver compared with the sham-implanted fish. On the basis of these general increases in enzyme activities, our results suggest that cortisol stimulates nitrogen metabolism in the sea raven. Amino acid catabolism may be a major source of substrate for gluconeogenesis and/or oxidation, while fatty acid mobilization may provide the fuel for endogenous use by the liver in cortisol-treated sea raven. These results further support the hypothesis that cortisol plays a role in the regulation of glucose production in stressed fish.

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