The Experts below are selected from a list of 849 Experts worldwide ranked by ideXlab platform
Daniel E. Crocker - One of the best experts on this subject based on the ideXlab platform.
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Adult male northern elephant seals maintain high rates of glucose production during extended breeding fasts
Journal of Comparative Physiology B, 2017Co-Authors: Daniel E. Crocker, Cory D. Champagne, Brian K. Wenzel, Dorian S. HouserAbstract:Many species undergo natural fasts as part of their life histories. Extended fasting is associated with increased β-oxidation of fatty acids and reduced oxidation of glucose to minimize commitment of body protein to gluconeogenesis. However, the metabolic strategies used to sustain extended fasts simultaneous with high rates of energy expenditure are not well understood. Studies in fasting adult female and weanling northern elephant seals (NES) have revealed high rates of endogenous glucose production (EGP) under constraints of high nutrient demand for lactation or development but relatively low rates of metabolism. These studies revealed low rates of glucose oxidation and high rates of glucose recycling through the Cori Cycle. We measured rates of glucose flux in fasting adult male NES to assess how significantly longer fasting durations, higher metabolic rates, and greater rates of muscular activity affect glucose kinetics. We measured glucose turnover in 18 adult males using the clearance of [6-H^3] glucose during breeding and molting. Adult male NES maintain high rates of EGP across extended fasts. EGP greatly exceeded estimated needs for glucose-dependent tissues, varied directly with plasma insulin and lactate concentrations, and was inversely related to plasma ketoacid concentrations. Together, these findings suggest that high rates of glucose production and recycling during breeding maintain high blood glucose levels to support glucose-dependent tissues while minimizing production of ketoacids and commitment of protein stores to glucose production.
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Adiposity and Fat Metabolism in Lactating and Fasting Northern Elephant Seals
Advances in Nutrition, 2014Co-Authors: Daniel E. Crocker, Cory D. Champagne, Melinda A. Fowler, Dorian S. HouserAbstract:Several taxa of animals fast completely from food and water during energy-intensive periods such as lactation, breeding, and development. In elephant seals, these behaviors are sustained by high adiposity, high rates of fat mobilization, and reduced oxidation of carbohydrates and proteins. Adiposity and the regulation of lipolysis directly affect lactation energetics, milk composition, and mating success. Long-term fasting induces changes in regulation of lipolysis and lipid metabolism that influence fatty acid (FA) availability and the onset of insulin resistance. Hypoinsulinemia and elevated circulating FAs are also associated with several unique features of carbohydrate metabolism, including elevated plasma glucose, gluconeogenesis, and Cori Cycle activity as well as high rates of pyruvate and tricarboxylic acid cycling. Glucose-lactate pools and triacylglycerol-FA Cycles may be linked via glyceroneogenesis and this may be an important pathway influencing both fat and carbohydrate metabolism. Together, these features allow a sustained, high intensity, fat-based metabolism without substantial accumulation of ketoacids.
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Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals (Mirounga angustirostris)
Journal of Comparative Physiology B, 2013Co-Authors: Stephen K. Tavoni, Cory D. Champagne, Dorian S. Houser, Daniel E. CrockerAbstract:Elephant seals maintain rates of endogenous glucose production (EGP) typical of post-absorptive mammals despite enduring prolonged periods of food deprivation concurrent with low rates of glucose oxidation. These high rates of EGP suggest extensive glucose recycling during fasting. We investigated lactate metabolism in fasting elephant seals to assess its role in glucose recycling. Whole-animal glucose and lactate fluxes were measured as the rates of appearance of glucose and lactate ( Ra _gluc and Ra _lac, respectively) using a primed constant infusion of [U-^14C] lactate and [6-^3H] glucose, and we calculated the minimum contribution of lactate to gluconeogenesis ( GNG _lac). Ra _lac was high compared to resting values in other species (3.21 ± 0.71 mmol min^−1* kg^−1), did not change between 14 ± 1 and 31 ± 8 days of fasting and varied directly with Ra _glu. The minimum GNG _lac was 44.6 ± 6.0 % of EGP, varied directly with plasma lactate levels, and did not change over the fast. Ra _ lac and Ra _ glu both varied directly with plasma insulin concentrations. These data suggest that lactate is the predominant gluconeogenic precursor in fasting elephant seals and that high rates of glucose recycling through Cori Cycle activity contribute to the maintenance of EGP during fasting. High levels of Cori Cycle activity and EGP may be important components of metabolic adaptations that maintain glucose production while avoiding ketosis during extended fasting or are related to sustained metabolic alterations associated with extended breath-holds in elephant seals.
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glucose production and substrate Cycle activity in a fasting adapted animal the northern elephant seal
The Journal of Experimental Biology, 2005Co-Authors: Cory D. Champagne, Dorian S. Houser, Daniel E. CrockerAbstract:SUMMARY During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose Cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose Cycle activity were investigated. Glucose Cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80±0.65 mg kg –1 min –1 early and 2.21±0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast ( t =5.27, 2.84; P =0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori Cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.
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Glucose production and substrate Cycle activity in a fasting adapted animal, the northern elephant seal.
The Journal of experimental biology, 2005Co-Authors: Cory D. Champagne, Dorian S. Houser, Daniel E. CrockerAbstract:During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose Cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose Cycle activity were investigated. Glucose Cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80+/-0.65 mg kg(-1) min(-1) early and 2.21+/-0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast (t=5.27, 2.84; P=0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori Cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.
Hiroshi Morisaki - One of the best experts on this subject based on the ideXlab platform.
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inhibition of the oxygen sensor phd2 in the liver improves survival in lactic acidosis by activating the Cori Cycle
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Tomohiro Suhara, Takako Hishiki, Masataka Kasahara, Noriyo Hayakawa, Tomoko Oyaizu, Tsuyoshi Nakanishi, Akiko Kubo, Hiroshi MorisakiAbstract:Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori Cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.
Tsuyoshi Nakanishi - One of the best experts on this subject based on the ideXlab platform.
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inhibition of the oxygen sensor phd2 in the liver improves survival in lactic acidosis by activating the Cori Cycle
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Tomohiro Suhara, Takako Hishiki, Masataka Kasahara, Noriyo Hayakawa, Tomoko Oyaizu, Tsuyoshi Nakanishi, Akiko Kubo, Hiroshi MorisakiAbstract:Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori Cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.
Masataka Kasahara - One of the best experts on this subject based on the ideXlab platform.
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inhibition of the oxygen sensor phd2 in the liver improves survival in lactic acidosis by activating the Cori Cycle
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Tomohiro Suhara, Takako Hishiki, Masataka Kasahara, Noriyo Hayakawa, Tomoko Oyaizu, Tsuyoshi Nakanishi, Akiko Kubo, Hiroshi MorisakiAbstract:Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori Cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.
Cory D. Champagne - One of the best experts on this subject based on the ideXlab platform.
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Adult male northern elephant seals maintain high rates of glucose production during extended breeding fasts
Journal of Comparative Physiology B, 2017Co-Authors: Daniel E. Crocker, Cory D. Champagne, Brian K. Wenzel, Dorian S. HouserAbstract:Many species undergo natural fasts as part of their life histories. Extended fasting is associated with increased β-oxidation of fatty acids and reduced oxidation of glucose to minimize commitment of body protein to gluconeogenesis. However, the metabolic strategies used to sustain extended fasts simultaneous with high rates of energy expenditure are not well understood. Studies in fasting adult female and weanling northern elephant seals (NES) have revealed high rates of endogenous glucose production (EGP) under constraints of high nutrient demand for lactation or development but relatively low rates of metabolism. These studies revealed low rates of glucose oxidation and high rates of glucose recycling through the Cori Cycle. We measured rates of glucose flux in fasting adult male NES to assess how significantly longer fasting durations, higher metabolic rates, and greater rates of muscular activity affect glucose kinetics. We measured glucose turnover in 18 adult males using the clearance of [6-H^3] glucose during breeding and molting. Adult male NES maintain high rates of EGP across extended fasts. EGP greatly exceeded estimated needs for glucose-dependent tissues, varied directly with plasma insulin and lactate concentrations, and was inversely related to plasma ketoacid concentrations. Together, these findings suggest that high rates of glucose production and recycling during breeding maintain high blood glucose levels to support glucose-dependent tissues while minimizing production of ketoacids and commitment of protein stores to glucose production.
-
Adiposity and Fat Metabolism in Lactating and Fasting Northern Elephant Seals
Advances in Nutrition, 2014Co-Authors: Daniel E. Crocker, Cory D. Champagne, Melinda A. Fowler, Dorian S. HouserAbstract:Several taxa of animals fast completely from food and water during energy-intensive periods such as lactation, breeding, and development. In elephant seals, these behaviors are sustained by high adiposity, high rates of fat mobilization, and reduced oxidation of carbohydrates and proteins. Adiposity and the regulation of lipolysis directly affect lactation energetics, milk composition, and mating success. Long-term fasting induces changes in regulation of lipolysis and lipid metabolism that influence fatty acid (FA) availability and the onset of insulin resistance. Hypoinsulinemia and elevated circulating FAs are also associated with several unique features of carbohydrate metabolism, including elevated plasma glucose, gluconeogenesis, and Cori Cycle activity as well as high rates of pyruvate and tricarboxylic acid cycling. Glucose-lactate pools and triacylglycerol-FA Cycles may be linked via glyceroneogenesis and this may be an important pathway influencing both fat and carbohydrate metabolism. Together, these features allow a sustained, high intensity, fat-based metabolism without substantial accumulation of ketoacids.
-
Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals (Mirounga angustirostris)
Journal of Comparative Physiology B, 2013Co-Authors: Stephen K. Tavoni, Cory D. Champagne, Dorian S. Houser, Daniel E. CrockerAbstract:Elephant seals maintain rates of endogenous glucose production (EGP) typical of post-absorptive mammals despite enduring prolonged periods of food deprivation concurrent with low rates of glucose oxidation. These high rates of EGP suggest extensive glucose recycling during fasting. We investigated lactate metabolism in fasting elephant seals to assess its role in glucose recycling. Whole-animal glucose and lactate fluxes were measured as the rates of appearance of glucose and lactate ( Ra _gluc and Ra _lac, respectively) using a primed constant infusion of [U-^14C] lactate and [6-^3H] glucose, and we calculated the minimum contribution of lactate to gluconeogenesis ( GNG _lac). Ra _lac was high compared to resting values in other species (3.21 ± 0.71 mmol min^−1* kg^−1), did not change between 14 ± 1 and 31 ± 8 days of fasting and varied directly with Ra _glu. The minimum GNG _lac was 44.6 ± 6.0 % of EGP, varied directly with plasma lactate levels, and did not change over the fast. Ra _ lac and Ra _ glu both varied directly with plasma insulin concentrations. These data suggest that lactate is the predominant gluconeogenic precursor in fasting elephant seals and that high rates of glucose recycling through Cori Cycle activity contribute to the maintenance of EGP during fasting. High levels of Cori Cycle activity and EGP may be important components of metabolic adaptations that maintain glucose production while avoiding ketosis during extended fasting or are related to sustained metabolic alterations associated with extended breath-holds in elephant seals.
-
glucose production and substrate Cycle activity in a fasting adapted animal the northern elephant seal
The Journal of Experimental Biology, 2005Co-Authors: Cory D. Champagne, Dorian S. Houser, Daniel E. CrockerAbstract:SUMMARY During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose Cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose Cycle activity were investigated. Glucose Cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80±0.65 mg kg –1 min –1 early and 2.21±0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast ( t =5.27, 2.84; P =0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori Cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.
-
Glucose production and substrate Cycle activity in a fasting adapted animal, the northern elephant seal.
The Journal of experimental biology, 2005Co-Authors: Cory D. Champagne, Dorian S. Houser, Daniel E. CrockerAbstract:During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose Cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose Cycle activity were investigated. Glucose Cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80+/-0.65 mg kg(-1) min(-1) early and 2.21+/-0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast (t=5.27, 2.84; P=0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori Cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.