Autoregulation of glucose production in men with a glycerol load during rest and exercise

2001 ◽  
Vol 280 (4) ◽  
pp. E657-E668 ◽  
Author(s):  
Jeff K. Trimmer ◽  
Gretchen A. Casazza ◽  
Michael A. Horning ◽  
George A. Brooks

Related to hepatic autoregulation we evaluated hypotheses that 1) glucose production would be altered as a result of a glycerol load, 2) decreased glucose recycling rate (Rr) would result from increased glycerol uptake, and 3) the absolute rate of gluconeogenesis (GNG) from glycerol would be positively correlated to glycerol rate of disappearance (Rd) during a glycerol load. For these purposes, glucose and glycerol kinetics were determined in eight men during rest and during 90 min of leg cycle ergometry at 45 and 65% of peak O2 consumption (V˙o 2 peak). Trials were conducted after an overnight fast, with exercise commencing 12 h after the last meal. Subjects received a continuous infusion of [6,6-2H2]glucose, [1-13C]glucose, and [1,1,2,3,3-2H5]glycerol without (CON) or with an additional 1,000 mg (rest: 20 mg/min; exercise: 40 mg/min) of [2-13C]- or unlabeled glycerol added to the infusate (GLY). Infusion of glycerol dampened glucose Rr, calculated as the difference between [6,6-2H2]- and [1-13C]glucose rates of appearance (Ra), at rest [0.35 ± 0.12 (CON) vs. 0.12 ± 0.10 mg · kg−1 · min−1 (GLY), P < 0.05] and during exercise at both intensities [45%: 0.63 ± 0.14 (CON) vs. 0.04 ± 0.12 (GLY); 65%: 0.73 ± 0.14 (CON) vs. 0.04 ± 0.17 mg · kg−1 · min−1 (GLY), P < 0.05]. Glucose Ra and oxidation were not affected by glycerol infusion at rest or during exercise. Throughout rest and both exercise intensities, glycerol Rdwas greater in GLY vs. CON conditions (rest: 0.30 ± 0.04 vs. 0.58 ± 0.04; 45%: 0.57 ± 0.07 vs. 1.19 ± 0.04; 65%: 0.73 ± 0.06 vs. 1.27 ± 0.05 mg · kg−1 · min−1, CON vs. GLY, respectively). Differences in glycerol Rd(ΔRd) between protocols equaled the unlabeled glycerol infusion rate and correlated with plasma glycerol concentration ( r = 0.97). We conclude that infusion of a glycerol load during rest and exercise at 45 and 65% ofV˙o 2 peak 1) does not affect glucose Ra or Rd, 2) blocks glucose Rr, 3) increases whole body glycerol Rd in a dose-dependent manner, and 4) results in gluconeogenic rates from glycerol equivalent to CON glucose recycling rates.

2002 ◽  
Vol 93 (1) ◽  
pp. 233-241 ◽  
Author(s):  
Jeff K. Trimmer ◽  
Jean-Marc Schwarz ◽  
Gretchen A. Casazza ◽  
Michael A. Horning ◽  
Nestor Rodriguez ◽  
...  

We evaluated the hypothesis that coordinated adjustments in absolute rates of gluconeogenesis (GNGab) and hepatic glycogenolysis (Gly) would maintain euglycemia and match glucose production (GP) to peripheral utilization during rest and exercise. Specifically, we evaluated the extent to which gradations in exercise power output would affect the contribution of GNGab to GP. For these purposes, we employed mass isotopomer distribution analysis (MIDA) and isotope-dilution techniques on eight postabsorptive (PA) endurance-trained men during 90 min of leg cycle ergometry at 45 and 65% peak O2 consumption (V˙o 2 peak; moderate and hard intensities, respectively) and the preceding rest period. GP was constant in resting subjects, whereas the fraction from GNG (fGNG) increased over time during rest (22.3 ± 0.9% at 11.25 h PA vs. 25.6 ± 0.9% at 12.0 h PA, P < 0.05). In the transition from rest to exercise, GP increased in an intensity-dependent manner (rest, 2.0 ± 0.1; 45%, 4.0 ± 0.4; 65%, 5.84 ± 0.64 mg · kg−1 · min−1, P < 0.05), although glucose rate of disappearance exceeded rate of appearance during the last 30 min of exercise at 65%V˙o 2 peak. Compared with rest, increases in GP were sustained by 92 and 135% increments in GNGab during moderate- and hard-intensity exercises, respectively. Correspondingly, Gly (calculated as the difference between GP and MIDA-measured GNGab) increased 100 and 203% over rest during the two exercise intensities. During moderate-intensity exercise, fGNG was the same as at rest; however, during the harder exercise fGNG decreased significantly to account for only 21% of GP. The highest sustained GNGab observed in these trials on PA men was 1.24 ± 0.3 mg · kg−1 · min−1. We conclude that, after an overnight fast, 1) absolute GNG rates increased with intensity of effort despite a reduced fGNG at 65% V˙o 2 peak, 2) during exercise Gly is more responsible than GNGab for maintaining GP, and 3) in 12-h fasted men, neither increased Gly or GNGab nor was their combination able to maintain euglycemia during prolonged hard (65%V˙o 2 peak) exercise.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S94-S95
Author(s):  
Abdulnaser Alkhalil ◽  
John L Clifford ◽  
Stacy-Ann Miller ◽  
Aarti Guatam ◽  
Marti Jett ◽  
...  

Abstract Introduction A mass exposure to irradiation would be a challenge to health care systems. A simple tool or test that indicates the intensity of the absorbed radiation or the chances of survivability would be invaluable in this scenario. To identify biomarkers that potentially could provide novel biodosimetry tools, we have conducted a radiation dose-response and time-course experiment in mice that includes an assessment of the transcriptome of the skin. Methods Groups of mice (n=5) received whole-body X-ray exposures (0, 1, 3, 6, or 20Gy) and skin biopsies were obtained from each animal at times post-irradiation (h2, Days 4, 7, 21, 28). Biopsies were collected from the 20Gy cohort for only days 0, 4, and 7. Total RNA was isolated and microarrays were performed and analyzed using custom R scripts to obtain lists of probe sets differentially expressed. Changes in gene expression at Benjamini-Hochberg FDR adjusted P &lt; 0.05 and FC &gt;2 were deemed significant. Analyses were performed comparing the different doses of X-ray exposure over all time points. Results Mice in the 20Gy group were euthanized by d7 and the dose was considered lethal. Animals in 1, 3, and 6Gy groups completed the full experiment to d28. Sammon plot analysis of transcriptomes showed clear separation of samples based on the irradiation levels and time after exposure. The clearest separation was between samples of lethal and sublethal doses. Samples from animals exposed to sublethal doses separated more based on timepoints rather than the IR dose suggesting a level of similarity in the progression of the response to sublethal doses. Downregulation was the dominant modulation in the significantly differentially transcribed genes (SDTGs) in the 20Gy group. Temporal changes in ratios of upregulated/downregulated SDTGs (P &lt; 0.05 and FC &gt; 2) revealed further the difference between of transcriptome responses after exposure to lethal and sublethal doses and indicated a delayed peaks response with increasing IR doses within the sublethal range. About 59% of the SDTGs in 20gy were common to all timepoints while no more than 11% were common at the same duration in the other groups. Ratios of the number of SDTGs at h2 to those common to all TPs decreased in a dose-dependent manner with potential radiation dosimetric applications. Conclusions These results demonstrate a solid ability in detecting IR exposure, differentiating lethal and sublethal exposures, and differentiating among the exposure to sublethal doses.


1979 ◽  
Vol 182 (2) ◽  
pp. 565-575 ◽  
Author(s):  
F Okajima ◽  
M Ui

1. A trace amount of glucose labelled with 14C uniformly and with 3H at position 2, 3 or 6 was injected intravenously into starved rats to measure the turnover rate of blood glucose. 2. Reliable estimates were made based on the semilogarithmic plot of specific radioactivity of the glucose contained in whole blood samples taken from the tail vein. 3. Glucose turned over more rapidly in hyperthyroid and more slowly in hypothyroid than in euthyroid rats. The percentage contribution of glucose recycling (determined from the difference in replacement rates between [U-14C]glucose and [6-3H]glucose) to the glucose utilization increased on induction of hyperthyroidism. 4. Futile cycles between glucose and glucose 6-phosphate (determined from the difference between replacement rates of [2-3H]glucose and [6-3H]glucose) were activated and inactivated by induction of hyperthyroid and hypothyroid states respectively. 5. The hepatic content of glycogen was much lower in hyper- and hypo-thyroid than in euthyroid rats. The enhanced glucose production in hyperthyroid rats resulted from not only activationof hepatic gluconeogenesis but also diversion of the final product of gluconeogenesis from liver glycogen to blood glucose. In hypothyroidism, the inhibition of gluconeogensis led to suppression of both glucose production and glycogenesis in the liver.


2003 ◽  
Vol 3 (2) ◽  
pp. 99-108
Author(s):  
Kermit G. Davis ◽  
Riley E. Splittstoesser ◽  
William S. Marras

Although there have been numerous studies evaluating the difference between stooped and squat lifting styles, there remains a lack of understanding of whole body kinematics during unrestricted lifting. The current study evaluated nine males and nine females while lifting two box weights (9.1 kg, 18.2 kg) from five origins below the waist (0, 19, 38, 57, and 76 cm above the floor) and from three task asymmetries (sagittally symmetric, 45° clockwise, 45° counter-clockwise). While the lifting style was significantly influenced by the height of lift origin and to a lesser extent gender, box weight, and task asymmetry, none of the conditions resulted in pure squat or stoop lifting style. However, for lifts above knee height, the lifting style resembled more of a stoop lift while lifts originating below knee height were more of a squat lift. As the origin moved closer to the floor, participants relied more on their hips to accomplish the sagittal flexion but overall adopted a more coordinated whole-body lifting style. All together, as more sagittal flexion is required, more joints are relied upon in a more coordinated effort. The current study indicates that caution needs to be exercised when applying results of pure squat or pure stoop lifting studies to free-style (realistic) lifting.


2013 ◽  
Vol 455 (2) ◽  
pp. 207-216 ◽  
Author(s):  
Kenneth K. Y. Cheng ◽  
Karen S. L. Lam ◽  
Yu Wang ◽  
Donghai Wu ◽  
Mingliang Zhang ◽  
...  

The adaptor protein APPL1 undergoes ubiquitination upon insulin stimulation in a TRAF6-dependent manner. Abrogation of APPL1 ubiquitination blocks insulin-evoked membrane localization of the APPL1–Akt complex, leading to impaired insulin actions on Akt activation and suppression of hepatic glucose production.


Diabetes ◽  
2006 ◽  
Vol 55 (3) ◽  
pp. 675-681 ◽  
Author(s):  
S. Chevalier ◽  
S. C. Burgess ◽  
C. R. Malloy ◽  
R. Gougeon ◽  
E. B. Marliss ◽  
...  

1980 ◽  
Vol 48 (6) ◽  
pp. 999-1007 ◽  
Author(s):  
K. Kabayashi ◽  
S. M. Horvath ◽  
F. J. Diaz ◽  
D. R. Bransford ◽  
B. L. Drinkwater

The time course of whole-body sweating and thermal regulation during rest and exercise in a hot humid environment was investigated in three body postures. After 45 min rest in the upright, low-sit, or supine posture, five unacclimatized men exercised for 45 min on a bicycle ergometer in the same posture in an environment of 49.5 degrees C, 28.9 Torr. Exercise was performed at two different work loads, corresponding to about 30 and 45% of VO2max. During exercise auditory canal temperature, rectal temperature, and mean skin temperature increased linearly being highest in the supine and lowest in the upright posture. Percentage of evaporated sweat from the skin to secreted sweat was 65% in upright, 52% in the low-sit, and only 46% in the supine posture during the last 20 min of exercise regardless of work load. The time course of the rate of body heat storage was different from predictions based on the thermal balance equation. Evaporative heat loss was not 100% effective in cooling the skin surface.


1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.


1996 ◽  
Vol 270 (1) ◽  
pp. E186-E191 ◽  
Author(s):  
K. F. Petersen ◽  
T. Price ◽  
G. W. Cline ◽  
D. L. Rothman ◽  
G. I. Shulman

Relative contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production during the first 12 h of a fast were studied in 13 healthy volunteers by noninvasively measuring hepatic glycogen content using 13C nuclear magnetic resonance spectroscopy. Rates of net hepatic glycogenolysis were calculated by multiplying the change in liver glycogen content with liver volume determined by magnetic resonance imaging. Rates of gluconeogenesis were calculated as the difference between rates of glucose production determined with an infusion of [6,6-2H]-glucose and net hepatic glycogenolysis. At 6 P.M. a liquid mixed meal (1,000 kcal; 60% as glucose) was given, to which [2-2H]glucose was added to trace glucose absorption. Hepatic glycogen content was measured between 11 P.M. and 1 A.M. and between 3 and 6 A.M. At 11 P.M. the concentration was 470 mM and it decreased linearly during the night. The mean liver volume was 1.47 +/- 0.06 liters. Net hepatic glycogenolysis (5.8 +/- 0.8 mumol.kg body wt-1.min-1) accounted for, on average, 45 +/- 6% and gluconeogenesis for 55 +/- 6% of the rate of whole body glucose production (12.6 +/- 0.6 mumol.kg body wt-1.min-1). In conclusion, this study shows that, even early in the phase of the postabsorptive period when liver glycogen stores are maximal, gluconeogenesis contributes approximately 50% to hepatic glucose production.


2001 ◽  
Vol 91 (3) ◽  
pp. 1099-1104 ◽  
Author(s):  
François Désy ◽  
Yan Burelle ◽  
Patrice Bélanger ◽  
Marielle Gascon-Barré ◽  
Jean-Marc Lavoie

The present study was conducted to examine the effect of a single bout of exercise (rodent treadmill, 60 min at 26 m/min, 0% grade) on the gluconeogenic activity of periportal hepatocytes (PP-H) and perivenous hepatocytes (PV-H) in fasted (18 h) rats. Isolated PP-H and PV-H, obtained by selective destruction following liver perfusion with digitonin and collagenase, were incubated with saturating concentrations of alanine (Ala; 20 mM) or a mixture of lactate and pyruvate (Lac+Pyr; 20:2 mM) to determine the glucose production flux ( J glucose) in the incubation medium. Results show that, in the resting conditions, J glucose from all exogenous substrates was significantly higher ( P < 0.01) in PP-H than in PV-H. Exercise, compared with rest, resulted in a higher J glucose ( P < 0.01) from Lac+Pyr substrate in the PV-H but not in the PP-H, resulting in the disappearance of the difference in J glucosebetween PP-H and PV-H. Exercise, compared with rest, led to a higher J glucose ( P < 0.01) from Ala substrate in both PP-H and PV-H. However, the exercise-induced increase in J glucose (gluconeogenic activity) from Ala substrate was higher in PV-H than in PP-H, resulting, as from Lac+Pyr substrate, in the disappearance ( P > 0.05) of the difference of J glucose between PP-H and PV-H. It is concluded that exercise differentially stimulates the gluconeogenic activity of PV-H to a larger extent than PP-H, indicative of a heterogenous metabolic response of hepatocytes to exercise.


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