Enhanced Uptake of Insulin and Glucagon by Liver in Rats Adapted to a High Protein Diet

Demigné, Christian; Fafournoux, Pierre; Rémésy, Christian

doi:10.1093/jn/115.8.1065

Cited by 22 publications

(5 citation statements)

References 28 publications

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“…Previous studies had reported a postprandial secretion of both insulin and glucagon in rats fed a HP diet (3,18). In that context, the respective influence of amino acids and insulin on glucagoninduced PEPCK and G6PC1 gene expression was investigated in vitro in primary cultures of isolated hepatocytes with constant concentration of glucose (5.5 mM).…”

Section: Discussionmentioning

confidence: 99%

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

Azzout‐Marniche¹,

Gaudichon²,

Blouet³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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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.high-protein diet; glyconeogenesis; glucose 6-phosphatase; phosphoenolpyruvate carboxykinase; liver THE CONSEQUENCES OF HIGH-PROTEIN feeding on the regulation and pathways of glucose disposal through glycogen metabolism and gluconeogenesis remain unclear. High-protein feeding induced both insulin and glucagon secretion in the fed state, associated with the repletion of glycogen stores (3, 45, 52), whereas excess dietary amino acids are metabolized within tissues and the derived nitrogen released into the circulation in the form of glutamine, alanine, serine, and glycine (28, 56). These amino acids are subsequently taken up by the liver, and the nitrogen is converted to urea and glutamine (12,28), the bulk of their carbon skeleton being converted to glucose through hepatic gluconeogenesis (8,29,37,51). This concomitant activation of both glycogen synthesis and gluconeogenesis in the fed state raises the question as to whether the glucose-6-P produced from gluconeogenic amino acid precursors could be directly channeled to glycogen through glycogenesis instead of being excreted as glucose from hepatocytes. This pathway of glyconeogenesis has been discussed over several decades, but despite some evidence during refeeding (49), its significance and molecular basis remain poorly understood (4, 30), and it has not previously been hypothesized under high-protein feeding.It is established that insulin stimulates glycogen synthesis and represses the gluconeogenic production of glucose, whereas glucagon represses glycogen synthesis and stimulates glucose ...

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Section: Discussionmentioning

confidence: 99%

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

Azzout‐Marniche¹,

Gaudichon²,

Blouet³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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show abstract

“…For this purpose, we studied the time course changes of energy metabolism during the transition from a normal to an HP diet in rats. Thus, we were able to follow the metabolic adjustments occurring during the 15-d period in which adaptation of protein and energy metabolism to the diet was achieved (36)(37)(38). 21 ) was added at the expense of sucrose and starch.…”

Section: Introductionmentioning

confidence: 99%

Postprandial Nutrient Partitioning but Not Energy Expenditure Is Modified in Growing Rats during Adaptation to a High-Protein Diet

Stępień

Gaudichon

Azzout‐Marniche

et al. 2010

The Journal of Nutrition

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It has been suggested that high-protein (HP) diets may favor weight management by lowering energy intake and reducing body fat. Whether these effects result from changes in energy metabolism remains unclear. We measured the adaptation of energy metabolism components during 2 wk of HP feeding. Fifty male Wistar rats were switched from a control diet to an HP diet (14 and 55% of protein, respectively) for 1, 3, 6, or 14 d. Energy expenditure (EE) and substrate oxidation were measured by indirect calorimetry in feed-deprived rats and after consumption of a test meal. EE components, including the thermic effect of feeding and activity, were not modified during adaptation to an HP diet. Nutrient oxidation in feed-deprived rats was not affected by HP feeding, except for an early increase in protein oxidation. After 1 d, the postprandial inhibition of lipid oxidation (Lox) was blunted, carbohydrate (CHO) oxidation decreased by one-half, and urea clearance decreased by 66%. Thereafter, CHO oxidation gradually rose, resulting in a null CHO balance. Lox and urea clearance recovered after 3 d of adaptation to an HP diet, while protein oxidation reached a plateau. The postprandial oxidation of CHO counterbalanced the amount of ingested CHO as soon as 3 d, leading to a null postprandial CHO balance. We conclude that the inhibition of de novo lipogenesis from dietary CHO, but not EE and Lox, may participate in limiting the adiposity induced by HP feeding. The transient changes occurring during the period of adaptation to the diet highlight that the duration of the diet is critical in HP diet studies.

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“…Our results clearly demonstrate that the fraction of intraportally infused insulin reaching the systemic circulation decreases with higher doses of insulin. This implies that the liver contains adaptable mechanisms to reduce the systemic insulin levels 119, 37,49]. These mechanisms are not only regulated by the portal insulin levels, but are also under the control of other factors [37,50].…”

Section: Discussionmentioning

confidence: 99%

Insulin Levels After Portal and Systemic Insulin Infusion Differ in a Dose-Dependent Fashion

Vos¹,

Haan²,

Vegter³

et al. 1998

Horm Metab Res

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The role of the liver in the regulation of systemic insulin levels is not well understood. The reported extraction rates vary between 0 to 85%, and extraction of a constant fraction of 50% of the portally delivered insulin is generally assumed. In the present study, we have investigated the role of the liver in the regulation of systemic insulin levels in the normal rat. Insulin was infused into the portal vein of conscious and freely moving rats in doses of 20, 40, 80 pmol/min during 15 min to mimic the gradual release of insulin by the native endocrine rat pancreas. The profiles of plasma insulin and glucose levels in the systemic circulation were compared to those obtained after direct infusion into the systemic circulation. The effect of intraportal and direct systemic infusion on plasma insulin and blood glucose levels were virtually similar where 20 pmol/min was applied. But, these effects were different if the dose was 40 pmol/min, and this difference increased when the dose was increased to 80 pmol/min, since hypoglycemia was less severe and normoglycemia was restored more rapidly with portal than with systemic infusion. Thus, our results show that the fraction of intraportally infused insulin reaching the systemic circulation decreases with higher doses of insulin. This suggests that the liver contains adaptable mechanisms to reduce the systemic insulin levels.

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Enhanced Uptake of Insulin and Glucagon by Liver in Rats Adapted to a High Protein Diet

Cited by 22 publications

References 28 publications

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

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

Postprandial Nutrient Partitioning but Not Energy Expenditure Is Modified in Growing Rats during Adaptation to a High-Protein Diet

Insulin Levels After Portal and Systemic Insulin Infusion Differ in a Dose-Dependent Fashion

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