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Review
. 2020 Aug 10;21(16):5733.
doi: 10.3390/ijms21165733.

The Precious Few Grams of Glucose During Exercise

George A Brooks  1
Affiliations
Review

The Precious Few Grams of Glucose During Exercise

George A Brooks. Int J Mol Sci. .

Abstract

As exercise intensity exceeds 65% of maximal oxygen uptake carbohydrate energy sources predominate. However, relative to the meager 4-5 g blood glucose pool size in a postabsorptive individual (0.9-1.0 g·L-1 × 5 L blood = 18-20 kcal), carbohydrate (CHO) oxidation rates of 20 kcal·min-1 can be sustained in a healthy and fit person for one hour, if not longer, all the while euglycemia is maintained. While glucose rate of appearance (i.e., production, Ra) from splanchnic sources in a postabsorptive person can rise 2-3 fold during exercise, working muscle and adipose tissue glucose uptake must be restricted while other energy substrates such as glycogen, lactate, and fatty acids are mobilized and utilized. If not for the use of alternative energy substrates hypoglycemia would occur in less than a minute during hard exercise because blood glucose disposal rate (Rd) could easily exceed glucose production (Ra) from hepatic glycogenolysis and gluconeogenesis. The goal of this paper is to present and discuss the integration of physiological, neuroendocrine, circulatory, and biochemical mechanisms necessary for maintenance of euglycemia during sustained hard physical exercise.

Keywords: euglycemia; exercise; glucose; homeostasis; lactate; metabolism.

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Conflict of interest statement

The author declare no conflict of interest.

Figures

Figure 1
Figure 1
Blood glucose concentration across time in resting and exercising young men. Values are means ± SE; n = 6 for untrained and trained groups. The inset shows steady-state rest and exercise glucose concentrations for each condition. LT, lactate threshold; LT-10%, 10% below the LT workload; LT-10% LC, 10% below the LT workload with a lactate clamp. ^ Significantly different from rest within condition (p < 0.05). * Significantly different from untrained (p < 0.05). £ Significantly different from trained LT (p < 0.05). Note that even in the young healthy cohort regular physical exercise (training) significantly decreases resting, 12 h, overnight fasted blood (glucose). Note also that in trained men blood (glucose) increased during hard exercise at the lactate threshold (LT), but that exogenous lactate infusion (lactate clamp, LC) decreases blood (glucose). From [11].
Figure 2
Figure 2
Energy generated from oxidation of carbohydrate (CHO) and lipid sources. Subjects were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Error bars, SE for total energy expenditure only; n = 10 subjects. Note that compared to rest, energy expenditure during exercise increases more than 10 times. Note also that at rest glucose oxidation represents approximately half of total CHO oxidation that represents only 25% of energy expenditure. During exercise glucose oxidation represents only 10–20% of total energy expenditure and approximately 25% of total CHO oxidation. From [14].
Figure 3
Figure 3
Blood glucose appearance rates (Ra), or flux in healthy young men during rest and exercise, before and after training. Subjects were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Values are means ± SE; n = 8–9. Note that compared to rest, exercise increases tracer-measured blood glucose rate of appearance 2–3 times. Comparing the second and third columns on the right in which men exercised at the same exercise power output before and after training, glucose Ra and Rd (not shown) decreased with training. However, the greatest glucose Ra was observed during hard, 65% VO2max exercise after training (last column). From [10].
Figure 4
Figure 4
Percentages of glucose Rd accounted for by leg net glucose uptake as a function of relative exercise intensity during rest and exercise in healthy young men, before and after training. Subjects were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Values are means of last 30 min of exercise for glucose Rd and 1 h of exercise for net glucose uptake ± SE; n = 6–8, same subjects as in Figure 3. Note the relatively large increase in leg muscle glucose uptake during exercise, especially after training when leg power output increased approximately 25% over pre-training exercise intensity. While this figure shows a relative shunt of available blood glucose to working muscle, as shown in Figure 2 the energy role of blood glucose to the overall metabolic response to exercise is small. From [10].
Figure 5
Figure 5
Fractional glucose extractions (%) determined from arterial-venous concentration differences (a–v) in resting and exercising young men, before and after endurance training. Subjects were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Values are means ± SE; n = 6–8, same subjects as in Figure 3 and Figure 4, but show variability due to variances around measuring arterial and venous blood glucose values. There does not appear to be a training-induced increase in resting or working muscle glucose fractional extraction. From [10].
Figure 6
Figure 6
Single leg blood flow rates in resting and exercising healthy young men from thermodilution at rest and during exercise, before and after training. Subjects were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Values are means ± SE; n = 6–8, same individuals and treatments as in Figure 3, Figure 4 and Figure 5. Exercise and exercise training increase leg muscle blood flow compared to rest and during the untrained condition. However, there does not appear to be a training-induced increase in resting or working muscle glucose fractional extraction (Figure 5). From [10].
Figure 7
Figure 7
(A) arterial insulin concentrations ((insulin)a) in healthy young men during rest and exercise, before and after training. Subjects (same as in Figure 3, Figure 4, Figure 5 and Figure 6) were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Values are means ± SE; n = 8–9. (B) Arterial glucagon concentrations ((glucagon)a) during rest and exercise, before and after training. (C) Arterial insulin-to-glucagon ratios ((insulin)a/(glucagon)a) during rest and exercise, before and after training. Endurance training has the effect of decreasing insulin and glucagon levels and the I/G. Insulin levels declined during exercise; glucagon rose in the hard 65% VO2peak condition before training, but otherwise remained unchanged or declined slightly during exercise. See text for discussion. From [10].
Figure 8
Figure 8
Plasma epinephrine (A,B) and norepinephrine (C,D) as functions exercise intensity as given by absolute (VO2) (A,C) and relative (to % VO2peak) (B,D). Untrained subjects (UT) were studied at the exercise power output that elicited the lactate threshold (LT). Trained subjects (T) studied at power outputs that elicited the LT, 10% below the LT (LT-10%), and LT-10% plus exogenous lactate infusion raising blood (lactate) (i.e., lactate clamp, LC) to that eliciting the LT (LT-10% + LC). Metabolic rates elicited at rest and exercise in the present and previous studies involving subjects with different physical fitness status. VO2max values (means ± SEM) of UT and T subjects are 3.7 ± 0.1 and 5.0 ± 0.3 L·min−1, respectively. Whether expressed as absolute or relative values both trained and untrained subjects respond to increments in exercise intensity with exponential increments in circulating catecholamines. From [21].
Figure 9
Figure 9
Plasma norepinephrine (A) and epinephrine (B) concentrations across time during rest and exercise. Shown are data for control (CON) and lactate clamp (LC) at 55% VO2peak; 65% indicates 65% VO2peak. Insets are mean rest and exercise for each condition. p < 0.05 is significantly different from CON (*) and significantly different from 65% (#). Results show a suppression of plasma catecholamine levels by exogenous lactate. See text for discussion. From [26].
Figure 10
Figure 10
(A) Percent glucose appearance rate (Ra) from gluconeogenesis (GNG) during rest and exercise, before and after training. (B) Estimated GNG during rest and exercise, before and after training. Subjects were studied at 45 and 65% of peak rate of oxygen consumption (VO2peak) before 9 week of endurance training (45% pre and 65% pre, respectively) and then after training at same absolute power output that elicited 65% VO2peak before training (65% old (absolute, ABT)) and same relative power output that elicited 65% VO2peak after training (65% new (relative, RLT)). Values are means ± SE; n = 8–9. Although most lactate formed during steady rate exercise is disposed of within working skeletal muscle and elsewhere in the body such as heart [44,46,48], gluconeogenesis (GNG) accounts for 20–25% of lactate disposal during exercise. Hence, GNG is a major avenue of lactate disposal and the most important GNG precursor during exercise. From [36].
Figure 11
Figure 11
Histograms of the absolute and relative contributions to total cerebral carbohydrate (CHO) from lactate, glucose from gluconeogenesis (GNG), and glucose from hepatic glycogenolysis in healthy control subjects (left, panels A,C), and traumatic brain injury (TBI) patients (right, panels B,D). Compared with panel (A,B) shows the decrease in cerebral metabolic rate for glucose (CMRgluc) following TBI, but also shows increased contributions of lactate and glucose from GNG to total cerebral CHO uptake after TBI. A comparison of panels (C) (control) and (D) (TBI) shows the large increase in percentage cerebral CHO uptake contributed by lactate, directly, or indirectly from GNG, following TBI. These figures demonstrate the direct and indirect means by which lactate and gluconeogenesis from lactate support the healthy as well as injured brain. From [47].
Figure 12
Figure 12
A mere 5 g, a teaspoon, of blood sugar (glucose) is regulated by a coordinated set of neuroendocrine responses involving both feed-forward and feedback components. For exercise the responses involve the sympathetic nervous system (SNS) and its capabilities via post-ganglionic nerves that release norepinephrine and the adrenal medulla that releases epinephrine for direct and endocrine signaling that initiate cardiopulmonary, cardiovascular, and other fight and flight autonomic responses. Cardiovascular control serves to direct the limited glucose supply where it is needed (heart, brain, working skeletal muscle), and shunt blood flow and glucose delivery away from other tissues. In the splanchnic bed the pancreas secretes insulin (β-cells), glucagon (α-cells), and somatostatin (δ-cells). As well, gastric secretion of ghrelin, GLP-1, and PYY affect appetite and eating behavior that provides major support of glycemia. Feedback control includes the Metaboreflex, secretion of myokines (e.g., IL-6) and lactate from working muscle, and changes in blood (glucose), as well as epinephrine from the adrenal medulla that inhibits pancreatic secretions. In adipose lipolysis is inhibited by lactate via c-AMP and CREB as well as TGF-β2 released from liver under the influence of circulating lactate. See text for details. Figure modified from [1] and other sources including [6].
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