Effects of infused fructose on endogenous glucose production, gluconeogenesis, and glycogen metabolism

Tounian, P.; Henry, Sylvie; Jéquier, E; Tappy, Luc

doi:10.1152/ajpendo.1994.267.5.e710

Cited by 37 publications

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“…Fructose is ef®ciently removed from the portal circulation by liver cells and is mainly stored as liver glycogen or converted to lactate in the liver, the lactate subsequently being oxidised in extrahepatic tissues. 27 These metabolic processes are non-insulindependent and do not increase plasma glucose concentrations. 27,28 Glucose is mainly oxidised in peripheral tissues and stored as glycogen in muscles and in the liver.…”

Section: Discussionmentioning

confidence: 99%

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Weight loss and changes in energy metabolism in massively obese adolescents

et al. 1999

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OBJECTIVE: To investigate the energy metabolism modi®cations induced by energy restriction and weight loss in massively obese adolescents. SUBJECTS: Ten massively obese girls (179 AE 31% of ideal body weight; age, 13.3 ± 16.4 y) after 2 ± 5 weeks on a lowenergy diet and 4.5 ± 11.5 months later, that is, after a substantial weight loss, and eight controls. MEASUREMENTS: Resting energy expenditure (REE) and carbohydrate-induced thermogenesis (CIT) after a sucrose load (by indirect calorimetry), plasma glucose and insulin before and after the sucrose load. RESULTS: After 2 ± 5 weeks on a low-energy diet, REE (7415 AE 904 kJad) was lower than the expected value calculated from the regression equation of REE on fat free mass in controls (P 0.005). After a 37 AE 17% reduction in excess weight, REE decreased (6405 AE 613 kJad) and remained lower than the expected value (P 0.005). At the early stages of weight loss, the area under the plasma glucose response curve was negatively correlated with CIT (r 7 0.80, P 0.01) and was higher in the six obese adolescents with low CIT than in the four with normal CIT (396 AE 52 vs 283 AE 26 mmol.l 71 .min 71 , P 0.01). After substantial weight loss, the area under the plasma insulin response curve decreased by 32% (P 0.02), and both CIT and the area under the plasma glucose response curve became similar in obese patients with low and normal CIT prior to weight loss. CONCLUSION: These results indicate that in massively obese adolescents, REE for fat-free mass is decreased at the very beginning of the process of losing weight and remains decreased as long as energy restriction and weight reduction carry on. They also indicate that the impaired CIT sometimes observed returns to normal after weight reduction suggesting that it is secondary to a decrease in glucose uptake induced by obesity-associated insulin resistance.

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Section: Discussionmentioning

confidence: 99%

“…27 These metabolic processes are non-insulindependent and do not increase plasma glucose concentrations. 27,28 Glucose is mainly oxidised in peripheral tissues and stored as glycogen in muscles and in the liver. 29 These metabolic processes are insulindependent and result in an elevation in plasma glucose concentrations.…”

Section: Discussionmentioning

confidence: 99%

Weight loss and changes in energy metabolism in massively obese adolescents

et al. 1999

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“…This infusion rate of fructose was selected in order to achieve plasma fructose levels of ϳ200 mol/l (26,27). Such low-circulating levels of fructose would be regulatory for GK translocation, without providing increased substrate for gluconeogenesis (28). However, to examine whether fructose infusion could directly influence the rates of glucose production or peripheral glucose uptake in the absence of changes in the counterregulatory hormones, we performed another set of studies in five healthy lean volunteers matched for age, BMI, and HbA 1c with the participants in the stepped hypoglycemia studies (three men and two women, BMI 23.1 Ϯ 2.81 kg/m 2 , HbA 1c 5.4 Ϯ 0.5%).…”

Section: Methodsmentioning

confidence: 99%

Fructose Amplifies Counterregulatory Responses to Hypoglycemia in Humans

et al. 2002

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Glucokinase (GK) is required for cellular glucose sensing, although there is a paucity of data regarding its role in the counterregulatory response to hypoglycemia in humans. Because fructose has been shown to modulate GK activity, we examined the effects of an acute infusion of fructose on hypoglycemia counterregulation in seven lean nondiabetic subjects. Using stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l target plasma glucose steps, 50 min each), subjects were studied on two separate occasions, without (control) or with co-infusion of fructose (1.2 mg ⅐ kg ؊1 ⅐ min ؊1 ). Fructose induced a resetting of the glycemic thresholds for secretion of epinephrine (3.8 ؎ 0.1 mmol/l) and glucagon (3.9 ؎ 0.2 mmol/l) to higher plasma glucose concentrations (4.0 ؎ 0.1 mmol/l [P ‫؍‬ 0.006] and 4.1 ؎ 0.1 mmol/l [P ‫؍‬ 0.03], respectively). In addition, the magnitude of increase in epinephrine and glucagon concentrations was higher after administration of fructose (48 and 39%, respectively, P < 0.05 for both). The amplification of these hormonal responses was specific because plasma norepinephrine, growth hormone, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-3 H]glucose, increased by 47% (P < 0.05) in the fructose infusion studies compared with 14% (P ‫؍‬ NS) in the control studies. In addition, glucose uptake was more suppressed with fructose infusion (by 33%, P < 0.05). In concert with these effects of fructose on glucose kinetics, average glucose infusion rate was markedly reduced in the fructose infusion studies during the 3.9-mmol/l glucose step (4.6 ؎ 0.9 vs. 7.4 ؎ 1.1 mol ⅐ kg ؊1 ⅐ min ؊1 , respectively, P ‫؍‬ 0.03) and during the 3.3-mmol/l glucose step (0.5 ؎ 0.1 vs. 5.2 ؎ 1.2 mol ⅐ kg ؊1 ⅐ min ؊1 , respectively, P < 0.001), suggesting more potent glucose counterregulation and improved recovery from hypoglycemia with fructose infusion. We conclude that infusion of a catalytic dose of fructose amplifies the counterregulatory response to hypoglycemia by both increases in hormonal activation and augmentation of glucose counterregulation in humans. Diabetes 51: 893-900, 2002

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“…Arguably even more daunting is the fact that over 12 million of our children, ages [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], are now classified as obese. Clearly we have surpassed the epidemic stage [2] and have now entered a serious multigenerational problem.…”

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confidence: 99%

“…Unlike glucose-6-phosphate, fructose-1-phosphate bypasses phosphofructokinase activity of glycolysis and is metabolized directly into two trioses (glyceraldehyde and dihydroxyacetone phosphate) by fructose-1-phosphate aldolase. It has been reported that these two trioses can enter gluconeogenesis for synthesis of a small amount of glucose [14] and contribute to hepatic glycogen stores [15]; however, little of this fructose-derived glucose enters the general circulation [16]. Alternatively, and more likely during the high insulin, post-prandial state, the two trioses are used for de novo fatty acid synthesis [17] and their energy capacity stored long-term as triacylglycerol in adipose tissue [18].…”

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confidence: 99%

The Hidden Costs of High Fructose Corn Syrup: Challenges to Energy Balance and Fat Mobilization from Adipose Tissue

Orl¹,

Garver²

2015

J Biomol Res Ther

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Surveys (NHANES), shows that over 78 million U.S. adults now meet the criteria as clinically obese, more than double the number from 20 years ago. Arguably even more daunting is the fact that over 12 million of our children, ages 2-19, are now classified as obese. Clearly we have surpassed the epidemic stage [2] and have now entered a serious multigenerational problem. Human obesity is a complex problem involving physiological, psychological and behavioral contributions [3]. Because of this complexity, many proposals have been presented as to how we arrived at this state. However, if we reduce the complexity of this human condition in terms of energy balance, our obesity dilemma can be summed by the first law of thermodynamics: for a system to remain in equilibrium, the amount of energy added to a system must equal the sum of the amount of energy lost due to work by the system (physical activity) plus the internal energy expenditure of the system (basal metabolic rate). Thus, a negative energy balance will draw from energy stores resulting in weight loss, whereas a positive energy balance will result in weight gain as the body stores unused energy for later periods of negative energy balance [4]. From this fundamental principle, it is not hard to see how over consumption of calorie-dense foods and a shift to a more sedentary lifestyle are fueling our obesity problem.Early in human evolution, our dietary needs were met from hunting/ gathering activities, which were subject to varying levels of energy output demands and seasonal influences [5]. The calories provided by hunting/gathering were sufficient to fulfill our immediate energy requirements and possibly a bit more for energy storage permitting longer times between meals. The need for energy storage became more critical as populations adopted migratory behaviors to seek new territories for growth and as agrarian cultures began to take foothold and became subject to climate variations from year to year. Climate variations are often referred to as "feast or famine" periods; when water and temperatures are optimal, agrarian activities flourished, however, when these same populations encountered drought and/or disease, food sources became sorely limited. The durations of these seasonal variations were unpredictable and survival of the population was dependent on inheritance of metabolic traits that provided advantages to weather the periods of limited food availability. These genetic traits favored individuals who could efficiently store excess calories consumed during times of plenty [6].The culmination of many years of metabolic research has provided an elegant and detailed map defining how consumed calories are processed. The metabolic handling of dietary calories depends on the molecular form of the calories ingested, e.g. carbohydrates or fats, our two primary energy sources. Carbohydrates represent our energy choice for the immediate and rapid production of ATP. When the intracellular energy charge is sufficiently elevated, ATP production slows and the ener...

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Effects of infused fructose on endogenous glucose production, gluconeogenesis, and glycogen metabolism

Cited by 37 publications

References 0 publications

Weight loss and changes in energy metabolism in massively obese adolescents

Weight loss and changes in energy metabolism in massively obese adolescents

Fructose Amplifies Counterregulatory Responses to Hypoglycemia in Humans

The Hidden Costs of High Fructose Corn Syrup: Challenges to Energy Balance and Fat Mobilization from Adipose Tissue

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