Measurements of Gluconeogenesis and Glycogenolysis: A Methodological Review

Chung, Stephanie T.; Chacko, Shaji; Sunehag, Agneta L.; Haymond, Morey W.

doi:10.2337/db15-0640

Cited by 69 publications

(47 citation statements)

References 123 publications

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“…When the [6,6‐ 2 H 2 ]‐glucose tracer undergoes degradation during glycolytic pathways, the deuteriums on C‐6 are mostly lost and undetectable, before being recycled up via the gluconeogenic pathway (Chung et al . ). Furthermore, because both labels are on the same carbon of [6,6‐ 2 H 2 ]‐glucose, any potential recycling of infused tracer (M+2 in this instance) will not interfere with the GNG measurement (M+1) (Chacko et al .…”

Section: Discussionmentioning

confidence: 97%

“…By assessing the average incorporation of deuterium on multiple glucose carbons, any potential error that results in inequality between the top and bottom half of glucose (if real) will probably be reduced (Chung et al . ). Furthermore, it has been shown that measured fractional GNG in overnight fasted individuals (similar to that used in the present study) was comparable when using the average deuterium incorporation method and the 13 C‐NMR method, which is not influenced by transaldolase exchange (Chung et al .…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore, it has been shown that measured fractional GNG in overnight fasted individuals (similar to that used in the present study) was comparable when using the average deuterium incorporation method and the 13 C‐NMR method, which is not influenced by transaldolase exchange (Chung et al . ).…”

Section: Discussionmentioning

confidence: 97%

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Gluconeogenesis during endurance exercise in cyclists habituated to a long‐term low carbohydrate high‐fat diet

Webster

Noakes

Chacko

et al. 2016

The Journal of Physiology

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114

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Key pointsr Blood glucose is an important fuel for endurance exercise. It can be derived from ingested carbohydrate, stored liver glycogen and newly synthesized glucose (gluconeogenesis).r We hypothesized that athletes habitually following a low carbohydrate high fat (LCHF) diet would have higher rates of gluconeogenesis during exercise compared to those who follow a mixed macronutrient diet.r We used stable isotope tracers to study glucose production kinetics during a 2 h ride in cyclists habituated to either a LCHF or mixed macronutrient diet.r The LCHF cyclists had lower rates of total glucose production and hepatic glycogenolysis but similar rates of gluconeogenesis compared to those on the mixed diet.r The LCHF cyclists did not compensate for reduced dietary carbohydrate availability by increasing glucose synthesis during exercise but rather adapted by altering whole body substrate utilization.Abstract Endogenous glucose production (EGP) occurs via hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) and plays an important role in maintaining euglycaemia. Rates of GLY and GNG increase during exercise in athletes following a mixed macronutrient diet; however, these processes have not been investigated in athletes following a low carbohydrate high fat (LCHF) diet. Therefore, we studied seven well-trained male cyclists that were habituated to either a LCHF (7% carbohydrate, 72% fat, 21% protein) or a mixed diet (51% carbohydrate, 33% fat, 16% protein) for longer than 8 months. After an overnight fast, participants performed a 2 h laboratory ride at 72% of maximal oxygen consumption. Glucose kinetics were measured at rest and during the final 30 min of exercise by infusion of [6,6-2 H 2 ]-glucose and the ingestion of 2 H 2 O tracers. Rates of EGP and GLY both at rest and during exercise were significantly lower in the LCHF group than the mixed diet group (Exercise EGP: LCHF, 6.0 ± 0.9 mg kg −1 min −1 , Mixed, 7.8 ± 1.1 mg kg −1 min −1 , P < 0.01; Exercise GLY: LCHF, 3.2 ± 0.7 mg kg −1 min −1 , Mixed, 5.3 ± 0.9 mg kg −1 min −1 , P < 0.01). Conversely, no difference was detected in rates of GNG between groups at rest or during exercise (Exercise: LCHF, 2.8 ± 0.4 mg kg −1 min −1 , Mixed, 2.5 ± 0.3 mg kg −1 min −1 , P = 0.15). We conclude that athletes on a LCHF diet do not compensate for reduced glucose availability via higher rates of glucose synthesis compared to athletes on a mixed diet. Instead, GNG remains relatively stable, whereas glucose oxidation and GLY are influenced by dietary factors. Abbreviations ASA24, automated self-administered 24 h recall; βHB, β-hydroxybutyrate; BMI, body mass index; CV, coefficient of variation; EGP, endogenous glucose production; FFA, free fatty acids; GLY, glycogenolysis; GNG, gluconeogenesis; HR, heart rate; HR max , maximum heart rate; LCHF, low carbohydrate high fat; MIDA, mass isotopomer distribution analysis; MUFA, monounsaturated fatty acids; PPO, peak power output; PUFA, polyunsaturated fatty acids; R a , rate of appearance; R d , rate of disappearance; RER, respira...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Gluconeogenesis during endurance exercise in cyclists habituated to a long‐term low carbohydrate high‐fat diet

Webster

Noakes

Chacko

et al. 2016

The Journal of Physiology

Self Cite

114

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“…However, organs such as brain utilize glucose as their preferred or only metabolic fuel supply. Gluconeogenesis is the process that provides glucose to these tissues from precursors such as glycerol, lactate, pyruvate, and glucogenic amino acids; it takes place primarily in the liver and in a specific area of renal cortex [35].…”

Section: Liver Metabolic Plasticity For Carbohydrates Lipids and Promentioning

confidence: 99%

High Protein Diet and Metabolic Plasticity in Non-Alcoholic Fatty Liver Disease: Myths and Truths

2019

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Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation within the liver affecting 1 in 4 people worldwide. As the new silent killer of the twenty-first century, NAFLD impacts on both the request and the availability of new liver donors. The liver is the first line of defense against endogenous and exogenous metabolites and toxins. It also retains the ability to switch between different metabolic pathways according to food type and availability. This ability becomes a disadvantage in obesogenic societies where most people choose a diet based on fats and carbohydrates while ignoring vitamins and fiber. The chronic exposure to fats and carbohydrates induces dramatic changes in the liver zonation and triggers the development of insulin resistance. Common believes on NAFLD and different diets are based either on epidemiological studies, or meta-analysis, which are not controlled evidences; in most of the cases, they are biased on test-subject type and their lifestyles. The highest success in reverting NAFLD can be attributed to diets based on high protein instead of carbohydrates. In this review, we discuss the impact of NAFLD on body metabolic plasticity. We also present a detailed analysis of the most recent studies that evaluate high-protein diets in NAFLD with a special focus on the liver and the skeletal muscle protein metabolisms.

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“…This study was designed to elucidate the mechanisms underlying the lower prevalence of fasting hyperglycemia and the relationship of hepatic to whole-body insulin sensitivity among Black and White women. During the normal postabsorptive state, glucose concentrations (70-99 mg/dl) are closely regulated by a network of neural, hormonal, and intracellular factors (26,27). In the presence of risk factors, such as obesity, disruption of this neurohormonal network regulation causes fasting hyperglycemia and increased rates of both components of hepatic glucose production: (a) higher rates of gluconeogenesis; and (b) resistance to insulin-mediated suppression of glycogenolysis (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Gluconeogenesis and risk for fasting hyperglycemia in Black and White women

Chung¹,

Courville²,

Onuzuruike³

et al. 2018

JCI Insight

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Black women, compared with White women, have high rates of whole-body insulin resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis. This dissociation of whole-body insulin resistance from fasting hyperglycemia may be explained by racial differences in gluconeogenesis, hepatic fat, or tissue-specific insulin sensitivity. Two groups of premenopausal federally employed women, without diabetes were studied. Using stable isotope tracers, [2H2O] and [6,62-H2]glucose, basal glucose production was partitioned into its components (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis ([2H5]glycerol) was measured. Indices of insulin sensitivity, whole-body (SI), hepatic (HISIGPR), and adipose tissue, were calculated. Hepatic fat was measured by proton magnetic resonance spectroscopy. Black women had less hepatic fat and lower fractional and absolute gluconeogenesis. Whole-body SI, HISIGPR, and adipose tissue sensitivity were similar by race, but at any given level of whole-body SI, Black women had higher HISIGPR. Therefore, fasting hyperglycemia may be a less common early pathological feature of prediabetes in Black women compared with White women, because gluconeogenesis remains lower despite similar whole-body SI.

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Measurements of Gluconeogenesis and Glycogenolysis: A Methodological Review

Cited by 69 publications

References 123 publications

Gluconeogenesis during endurance exercise in cyclists habituated to a long‐term low carbohydrate high‐fat diet

Gluconeogenesis during endurance exercise in cyclists habituated to a long‐term low carbohydrate high‐fat diet

High Protein Diet and Metabolic Plasticity in Non-Alcoholic Fatty Liver Disease: Myths and Truths

Gluconeogenesis and risk for fasting hyperglycemia in Black and White women

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