Effects of Plasma Glucose Concentration on Glucose Utilization and Glucose Clearance in Normal Man

Verdonk, Carlos A.; Rizza, Robert A.; Gerich, John E.

doi:10.2337/diab.30.6.535

Cited by 117 publications

(26 citation statements)

References 9 publications

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“…This is consistent with our previous work demonstrating that acute supplementation of glucose does not lead to an increase in circulating glucose levels [18]. This is also consistent with other work demonstrating that low circulating blood glucose leads to rapid blood glucose clearance in humans after a bolus of glucose [28], and ketone bodies are rapidly cleared from plasma in rats under calorie-restricted conditions [29]. Rapid blood glucose clearance is associated with increased cerebral glucose utilization and seizures [18, 30].…”

Section: Discussionsupporting

confidence: 93%

Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice

Meidenbauer

Roberts

2014

Epilepsy & Behavior

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Dietary therapy has been used to treat many individuals with epilepsy that are refractory to anti-epileptic drugs. The mechanisms for how dietary therapy confers seizure protection are currently not well understood. We evaluated the acute effects of glucose and β-hydroxybutyrate (the major circulating ketone body) in conferring seizure protection to the EL mouse, a model of multifactorial idiopathic generalized epilepsy. EL mice were fed either a standard diet unrestricted or a calorie-restricted standard diet to achieve a body weight reduction of 20–23%. D-glucose, 2-deoxy-D-glucose, and β-hydroxybutyrate were supplemented in the drinking water of calorie-restricted mice for 2.5 hours prior to seizure testing to simulate the effect of increased glucose availability, decreased glucose utilization, and increased ketone availability, respectively. Seizure susceptibility, body weight, plasma glucose and β-hydroxybutyrate were measured over a nine-week treatment period. Additionally, excitatory and inhibitory amino acids were measured in the brains of mice using 1H NMR. Glutamate decarboxylase activity was also measured to evaluate the connection between dietary therapy and brain metabolism. We found that lowering of glucose utilization is necessary to confer seizure protection with long-term (>4 weeks) calorie restriction, whereas increased ketone availability did not affect seizure susceptibility. In the absence of long-term calorie restriction, however, reduced glucose utilization and increased ketone availability did not affect seizure susceptibility. Brain excitatory and inhibitory amino acid content did not change with treatment, and glutamate decarboxylase activity was not associated with seizure susceptibility. We demonstrate that reduced glucose utilization is necessary to confer seizure protection under long-term calorie restriction in EL mice, while acute ketone supplementation did not confer seizure protection. Further studies are needed to uncover the mechanisms by which glucose utilization influences seizure susceptibility.

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Section: Discussionsupporting

confidence: 93%

Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice

Meidenbauer

Roberts

2014

Epilepsy & Behavior

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“…This nonlinear relationship between transport and concentration has been previously reported for FFA (13) and also applies to glucose (27). We found that oleate clearance is higher during intravenous niacin infusion compared with saline infusion in healthy volunteers; this occurs in the context of a marked decrease in oleate concentration and no change in insulin concentrations (R.H.N.…”

Section: Discussionsupporting

confidence: 77%

Kinetics of Saturated, Monounsaturated, and Polyunsaturated Fatty Acids in Humans

et al. 2013

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Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase–generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.

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“…To define the efficiency with which this glucose was metabolized, the metabolic clearance rate (MCR) of glucose was calculated by dividing the amount of glucose metabolized (M) by the plasma glucose concentration. Although this calculation may not be valid when the insulin infusion rate and steady‐state insulin levels are lower than in this study, 12, 13 its use has been validated under the conditions we employed 14, 15 …”

Section: Methodsmentioning

confidence: 99%

Effect of Age on Glucose Tolerance, Insulin Secretion, and in Vivo Insulin Action

Rosenthal

Doberne

Greenfield

et al. 1982

J American Geriatrics Society

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The effect of age on glucose tolerance, insulin secretion, and in vivo insulin action (insulin clamp) was studied in 48 nonobese subjects, all of whom were fully ambulatory and in good general health. The observed age-related increase in fasting plasma glucose (r = 0.35, P less than 0.01) was not due to an increase in relative body weight (RBW). Plasma insulin levels, both fasting and postprandial, tended to rise with age, but these changes were not significant. There was a marginally significant correlation (r = -0.21) between age and insulin-stimulated glucose utilization, which fell to -0.13 when controlled for RBW. However, steady-state insulin levels during the insulin-clamp period were higher in the older subjects, suggesting that age leads to an impairment in insulin catabolism; thus it is likely that the impairment of in vivo insulin action with age was underestimated. The variation in in vivo action between individuals was much greater among the older subjects. It was concluded that the glucose intolerance associated with aging is of relatively minor magnitude when ambulatory, generally healthy, nonobese, and nondiabetic subjects are studied. The cause of the glucose intolerance associated with aging seems to be loss of normal in vivo insulin action. On the other hand, this defect is not shared by all older persons, and in many over the age of 70, glucose transport is as efficient as in persons in their 20s.

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Effects of Plasma Glucose Concentration on Glucose Utilization and Glucose Clearance in Normal Man

Cited by 117 publications

References 9 publications

Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice

Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice

Kinetics of Saturated, Monounsaturated, and Polyunsaturated Fatty Acids in Humans

Effect of Age on Glucose Tolerance, Insulin Secretion, and in Vivo Insulin Action

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