NMR Determination of Intracerebral Glucose Concentration and Transport Kinetics in Rat Brain

The concentration of intracerebral glucose as a function of plasma glucose concentration was measured in rats by 13C NMR spectroscopy. Measurements were made in 20–60 min periods during the infusion of [1-13C]d-glucose, when intracerebral and plasma glucose levels were at steady state. Intracerebral glucose was found to vary from 0.7 to 19 μmol g−1 wet weight as the steady-state plasma glucose concentration was varied from 3 to 62 m M. A symmetric Michaelis–Menten model was fit to the brain and plasma glucose data with and without an unsaturable component, yielding the transport parameters Km, Vmax, and Kd. If it is assumed that all transport is saturable ( Kd = 0), then Km = 13.9 ± 2.7 m M and Vmax/ Vgly = 5.8 ± 0.8, where Vgly is the rate of brain glucose consumption. If an unsaturable component of transport is included, the transport parameters are Km = 9.2 ± 4.7 m M, Vmax/ Vgly = 5.3 ± 1.5, and Kd/ Vgly = 0.0088 ± 0.0075 ml μmol−1. It was not possible to distinguish between the cases of Kd = 0 and Kd > 0, because the goodness of fit was similar for both. However, the results in both cases indicate that the unidirectional rate of glucose influx exceeds the glycolytic rate in the basal state by 2.4-fold and as a result should not be rate limiting for normal glucose utilization.

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Regulation of placental metabolism by glucose supply

Reproduction Fertility and Development ◽

10.1071/rd9950365 ◽

1995 ◽

Vol 7 (3) ◽

pp. 365 ◽

Cited By ~ 40

Author(s):

WW Hay

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Glucose Consumption ◽

Maternal Plasma ◽

Plasma Glucose Concentration ◽

Transporter Proteins ◽

Fetal Plasma ◽

Carbon Substrates ◽

Glucose Supply

Glucose is supplied to the placenta and fetus from the maternal plasma according to concentration-dependent mechanisms exhibiting saturation kinetics that are mediated by facilitative transporter proteins on both the maternal-facing microvillus and fetal-facing basal trophoblast membranes. Placental glucose transport to the fetus requires a net maternal-to-fetal plasma glucose concentration gradient that is determined by placental as well as fetal glucose consumption. Fetal plasma glucose concentration, independent of maternal glucose concentration, regulates the partition of placental glucose uptake into transfer to the fetus and consumption by the placenta. Placental transport capacity increases with advancing gestation, probably by an increased number of transporter proteins as surface area increases. Placental glucose consumption contributes to most or all of placental lactate and fructose production and other less well defined non-oxidative pathways of carbon metabolism. Placental glucose consumption accounts for at least 50% of placental oxygen consumption which remains independent of short-term or long-term changes in placental glucose supply, thus requiring varying amounts of other carbon substrates. Placental glucose supply, therefore, plays a key role in regulating placental glucose metabolism and placental carbon balance, and interacts reciprocally with other carbon substrates to maintain placental oxidative metabolism.

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Glucose Disposal of Low Birth Weight Infants: Steady State Hyperglycemia Produced by Constant Intravenous Glucose Infusion

PEDIATRICS ◽

10.1542/peds.63.3.389 ◽

1979 ◽

Vol 63 (3) ◽

pp. 389-396 ◽

Cited By ~ 3

Author(s):

Richard M. Cowett ◽

William Oh ◽

Arnold Pollak ◽

Robert Schwartz ◽

Barbara S. Stonestreet

Keyword(s):

Steady State ◽

Birth Weight ◽

Low Birth Weight ◽

Gestational Age ◽

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Insulin ◽

Plasma Glucose Concentration ◽

Glucose Disposal ◽

Osmotic Diuresis

Tolerance for glucose was studied in 35 well, appropriate for gestational age, low birth weight (LBW) infants (mean birth weight, 1,216 gm; mean gestational age, 30 weeks) between 3 and 38 days of age. Infants were given a graded dose of glucose at 8.1, 11.2, or 14.0 mg/kg/min for three hours by continuous peripheral intravenous infusion. Plasma glucose and insulin, and timed urine glucose and volume were measured. A steady state of plasma glucose concentration was noted by one hour at all infusion rates. In the nine infants receiving 8.1 mg/kg/min, plasma glucose and insulin were similar to the baseline values during the steady state, and none of these infants evidenced glucosuria. In the 16 infants receiving 11.2 mg/kg/min, the plasma glucose concentration significantly increased (140 to 166 mg/dl) during the steady state but the plasma insulin levels were not significantly different compared to baseline. Half of these infants developed hyperglycemia (plasma glucose 150 mg/dl) and glucosuria. Ten infants receiving 14.0 mg/kg/min developed a significantly higher plasma glucose and plasma insulin response in colmparison to those infants who received 8.1 and 11.2 mg/kg/min, and all evidenced hyperglycemia and glucosuria. Glucosuria did not exceed 6.4 mg/kg/hr (0.1 mg/kg/min) so that glucose disposal (retention) exceeded 99% of intake, and an osmotic diuresis was not noted in those infants who had glucosuria. Our data suggested that in well LBW infants, a three-hour infusion of glucose up to 14.0 mg/kg/min (approximately 80 kcal/kg/day) did not produce an osmotic diuresis, but in the highest infusion group (14 mg/kg/min), hyperglycemia did occur. The effect of hyperglycemia in the neonate is unknown and needs to be investigated.

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One-hour postload plasma glucose concentration in people with normal glucose homeostasis predicts future diabetes mellitus: a 12-year community-based cohort study

Clinical Endocrinology ◽

10.1111/cen.13280 ◽

2016 ◽

Vol 86 (4) ◽

pp. 513-519 ◽

Cited By ~ 20

Author(s):

Tae Jung Oh ◽

Soo Lim ◽

Kyoung Min Kim ◽

Jae Hoon Moon ◽

Sung Hee Choi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Cohort Study ◽

Glucose Homeostasis ◽

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Glucose Concentration ◽

Community Based ◽

Normal Glucose ◽

Future Diabetes

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Steady state glucose kinetics and their relation to plasma glucose concentration in the premature and full term neonatal piglet

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y81-163 ◽

1981 ◽

Vol 59 (10) ◽

pp. 1069-1072 ◽

Cited By ~ 2

Author(s):

P. A. Flecknell ◽

R. Wootton ◽

Muriel John ◽

J. P. Royston

Keyword(s):

Steady State ◽

Plasma Glucose ◽

Glucose Concentration ◽

Turnover Rate ◽

Full Term ◽

Plasma Glucose Concentration ◽

Human Infant ◽

Glucose Turnover ◽

Glucose Kinetics ◽

Neonatal Piglet

Steady state glucose kinetics were measured in 19 premature and 16 full-term piglets. Bodyweight, plasma glucose concentration, total body glucose turnover rate, and glucose pool size were not significantly different between the two groups. This suggests that the premature piglet is capable of maintaining glucose homeostasis during the first 24 h of life. Although there appeared to be a correlation between glucose turnover and plasma glucose concentration, analysis of covariance showed that it was spurious, suggesting that glucose utilization proceeds independently of the glucose concentration in plasma.Glucose turnover rate in the premature piglet is closely comparable with that reported in the premature human infant. These findings encourage the use of the neonatal piglet as an animal model for the study of the problems of the neonatal human.

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Lack of relationship between opioid-induced changes in fetal breathing and plasma glucose levels

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.269.3.r702 ◽

1995 ◽

Vol 269 (3) ◽

pp. R702-R707

Author(s):

H. H. Szeto ◽

P. Y. Cheng ◽

Y. Soong ◽

D. L. Wu

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Glucose Concentration ◽

Glucose Regulation ◽

Fetal Sheep ◽

Receptor Selectivity ◽

Fetal Plasma ◽

Glucose Levels ◽

Fetal Breathing ◽

Induced Changes

The mechanisms by which opioids increase or decrease fetal breathing remain unclear. Fetal plasma glucose is known to modulate breathing activity, and opioids have been reported to alter glucose regulation in the adult. In this study, we investigated whether alterations in fetal breathing by opioids may be explained by changes in plasma glucose levels. We compared the effects of morphine (nonselective), [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-selective), and [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) on fetal breathing and plasma glucose in unanesthetized fetal sheep. Whereas morphine at 1.2 and 5.0 mg/h iv resulted in an increase in breath number (P < 0.01), plasma glucose was decreased after 1.2 mg/h (P = 0.006) but increased after 5.0 mg/h (P = 0.008). DAMGO (100 micrograms/h icv) increased plasma glucose (P = 0.001) but reduced fetal breathing (P < 0.001). In contrast, DPDPE (30 micrograms/h icv) increased fetal breathing (P = 0.026) but had no effect on plasma glucose concentration. These data demonstrate that the actions of opioids on fetal glucose regulation and breathing are dependent on dose and receptor selectivity. However, there is no relationship between the effects of opioids on fetal breathing and plasma glucose concentration.

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Plasma glucose concentration 60 min post oral glucose load and risk of type 2 diabetes and cardiovascular disease: Pathophysiological implications

Diabetes and Vascular Disease Research ◽

10.1177/1479164119827239 ◽

2019 ◽

Vol 16 (4) ◽

pp. 337-343

Author(s):

Fahim Abbasi ◽

Paul JW Tern ◽

Gerald M Reaven

Keyword(s):

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Impaired Fasting Glucose ◽

Plasma Glucose ◽

Glucose Concentration ◽

Fasting Glucose ◽

Normal Glucose Tolerance ◽

Plasma Glucose Concentration ◽

Oral Glucose ◽

Normal Glucose

Aim: The aim of this study was to gain insight into the pathophysiological significance of elevated plasma glucose concentrations (mmol/L) 60 min post oral glucose load in apparently healthy individuals. Methods: Comparison of resistance to insulin action and associated cardio-metabolic risk factors in 490 apparently healthy persons, subdivided into those with a plasma glucose concentration 60 min following a 75-g oral glucose challenge of <8.6 versus ⩾8.6. Results: Insulin resistance was significantly greater in persons with normal glucose tolerance whose 60-min glucose concentration was ⩾8.6, associated with higher blood pressure, plasma concentrations of glucose, insulin, triglyceride and lower high-density lipoprotein cholesterol concentrations. Similar differences were seen in persons with impaired fasting glucose, but not in those with impaired glucose tolerance or both impaired fasting glucose and impaired glucose tolerance. The group whose 60-min glucose was <8.6 ( n = 318) contained primarily persons with normal glucose tolerance (88%), whereas the majority of those whose 60-min value was ⩾8.6 ( n = 172) had prediabetes (59%) and in particular combined impaired fasting glucose and impaired glucose tolerance. Conclusion: Plasma glucose concentration of ⩾8.6 mmol/L 60 min post oral glucose identifies higher proportions of combined impaired fasting glucose and impaired glucose tolerance individuals as well as normal glucose tolerance and impaired fasting glucose individuals with a more adverse cardio-metabolic profile, contributing to observed increased overall risk of type 2 diabetes and other metabolic diseases.

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Modeling the Dependence of Hexose Distribution Volumes in Brain on Plasma Glucose Concentration: Implications for Estimation of the Local 2-Deoxyglucose Lumped Constant

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.50 ◽

1991 ◽

Vol 11 (2) ◽

pp. 171-182 ◽

Cited By ~ 41

Author(s):

James E. Holden ◽

Kentaro Mori ◽

Gerald A. Dienel ◽

Nancy F. Cruz ◽

Thomas Nelson ◽

...

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Time Course ◽

Full Range ◽

Specific Radioactivity ◽

Plasma Glucose Concentration ◽

Glucose Content ◽

Glucose Levels ◽

Constant Change ◽

Lumped Constant

The steady-state distribution volumes of glucose, 3- O-methylglucose, and 2-deoxyglucose (2DG) are known to change as the concentration of glucose in plasma ranges from hypo- to hyperglycemic values. Model estimates of the three distribution volumes were compared with distribution volume values experimentally measured in the brains of conscious rats as the concentration of glucose in plasma was varied from 2 to 28 m M. The dependence on plasma glucose concentration of the 2DG lumped constant, the factor that relates the phosphorylation rate of 2DG to the net rate of glucose utilization at unit specific radioactivity in the plasma, had been determined previously in separate series of experiments. The model was extended to incorporate this dependence of the lumped constant. In the model both the transport and the phosphorylation barriers were assumed to be single and saturable. The values of their respective half-saturation concentrations and the ratio of the two maximum velocities for glucose were assumed to be invariant over the entire range of plasma glucose concentration. Good agreement between measured and estimated values for the distribution volumes and the lumped constant was attained over the full range of plasma glucose concentration. The model estimates reflected the progressive transport limitation of the brain glucose content as plasma glucose levels were reduced to hypoglycemic values. The results also indicated that these changes should be evident in the time course of 2DG in brain following administration by bolus or continuous infusion, and thus that indexes of local lumped constant change could be derived from the time course data.

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Influence of Plasma Glucose Concentration on Lumped Constant of the Deoxyglucose Method: Effects of Hyperglycemia in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1990.134 ◽

1990 ◽

Vol 10 (6) ◽

pp. 765-773 ◽

Cited By ~ 64

Author(s):

Franz Schuier ◽

Francesco Orzi ◽

Sumio Suda ◽

Giovanni Lucignani ◽

Charles Kennedy ◽

...

Keyword(s):

Plasma Glucose ◽

Glucose Concentration ◽

Full Range ◽

Brain Structures ◽

Plasma Glucose Concentration ◽

Glucose Levels ◽

Lumped Constant ◽

Arterial Plasma ◽

The Brain ◽

Deoxyglucose Method

The lumped constant of the deoxyglucose method was determined by the steady-state, model-independent method in the brain of normal conscious rats with arterial plasma glucose concentrations varying from normoglycemia (i.e., 8 m M) to hyperglycemia (i.e., 31 m M). The lumped constant for brain was found to decrease very gradually with increasing arterial plasma glucose concentration from a value of ∼0.45 in the midnor-moglycemic range (i.e., 7–8 m M) to ∼0.38 at 28–31 m M. 3- O-[14C]Methylglucose was used to assess the distribution of glucose within the brain structures in hyperglycemia; the results indicated that the glucose concentration, and therefore also the values for the lumped constant, remain relatively uniform in hyperglycemia with arterial plasma glucose concentrations as high as 34 m M. The values for the lumped constant for rat brain determined in the present studies were combined with those previously determined in this laboratory for hypoglycemia and normoglycemia by the same method to provide a single source for the values for the lumped constant to be used over the full range of arterial plasma glucose concentrations. In several rats the lumped constant for cephalic extracerebral tissues was also evaluated in parallel with those for the brain. The lumped constant for the cephalic extracerebral tissues was found to be about twice that for brain and to be unaffected by changes in arterial plasma glucose levels.

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