The Effect of Exercise Intensity on Carbohydrate Sparing Postexercise: Implications for Postexercise Hypoglycemia.

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations.

Glucose requirements to maintain euglycemia after moderate-intensity afternoon exercise in adolescents with type 1 diabetes are increased in a biphasic manner.

CONTEXT: Exercise increases the risk of hypoglycemia in type 1 diabetes. OBJECTIVE: This study aimed to investigate how the amount of glucose required to prevent an exercise-mediated fall in glucose level changes over time in adolescents with type 1 diabetes. SETTING: The study took place at a tertiary pediatric referral center. DESIGN, PARTICIPANTS, AND INTERVENTION: Nine adolescents with type 1 diabetes mellitus (five males, four females, aged 16 +/- 1.8 yr, diabetes duration 8.2 +/- 4.1 yr, hemoglobin A1c 7.8 +/- 0.8%, mean +/- SD) were subjected on two different occasions to a rest or 45 min of exercise at 95% of their lactate threshold. Insulin was administered iv at a rate based on their usual insulin dose, with similar plasma insulin levels for both studies (82.1 +/- 19.0, exercise vs. 82.7 +/- 16.4 pmol/liter, rest). Glucose was infused to maintain euglycemia for 18 h. MAIN OUTCOME MEASURES: Glucose infusion rates required to maintain euglcycemia and levels of counterregulatory hormones were compared between rest and exercise study nights. RESULTS: Glucose infusion rates to maintain stable glucose levels were elevated during and shortly after exercise, compared with the rest study, and again from 7-11 h after exercise. Counterregulatory hormone levels were similar between exercise and rest studies except for peaks in the immediate postexercise period (epinephrine, norepinephrine, GH, and cortisol peaks: 375.6 +/- 146.9 pmol/liter, 5.59 +/- 0.73 nmol/liter, 71.9 +/- 14.8 mIU/liter, and 558 +/- 69 nmol/liter, respectively). CONCLUSIONS: The biphasic increase in glucose requirements to maintain euglycemia after exercise suggests a unique pattern of early and delayed risk for nocturnal hypoglycemia after afternoon exercise.

Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1.

Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.

The 10-s maximal sprint: a novel approach to counter an exercise-mediated fall in glycemia in individuals with type 1 diabetes.

OBJECTIVE: To investigate whether a short maximal sprint can provide another means to counter the rapid fall in glycemia associated with moderate-intensity exercise in individuals with type 1 diabetes and therefore decrease the risk of early postexercise hypoglycemia. RESEARCH DESIGN AND METHODS: In the study, seven male subjects with type 1 diabetes injected their normal insulin dose and ate their usual breakfast. When their postprandial glycemia fell to approximately 11 mmol/l, they pedaled at 40% Vo(2peak) for 20 min on a cycle ergometer then immediately engaged in a maximal 10-s cycling sprint (sprint trial) or rested (control trial); the sprint and rest trials were administered in a counterbalanced order. RESULTS: Moderate-intensity exercise resulted in a significant fall (P < 0.05) in glycemia in both trials (means +/- SE: 3.6 +/- 0.5 vs. 3.1 +/- 0.5 mmol/l for sprint and control, respectively). The subsequent short cycling sprint opposed a further fall in glycemia for 120 min, whereas in the absence of a sprint, glycemia decreased further (3.6 +/- 1.22 mmol/l; P < 0.05) after exercise. The stabilization of glycemia in the sprint trial was associated with elevated levels of catecholamines, growth hormone, and cortisol. In contrast, these hormones remained at stable or near-stable levels in the control trial. Changes in insulin and free fatty acid levels were similar in the sprint and control trials. CONCLUSIONS: These results suggest that after moderate-intensity exercise, it is preferable for young individuals with insulin-treated, complication-free type 1 diabetes to engage in a 10-s maximal sprint to acutely oppose a further fall in glycemia than to only rest. The addition of the sprint after moderate-intensity exercise provides another means to reduce the risk of hypoglycemia in active individuals with type 1 diabetes.

Fasting decreases free fatty acid turnover in mice overexpressing skeletal muscle lipoprotein lipase.

Skeletal muscle lipoprotein lipase (LPL) overexpression in mice results in whole-body insulin resistance and increased intramuscular triglyceride stores, but decreased plasma triglyceride concentration and unchanged plasma free fatty acid (FFA) concentration. The effects of skeletal muscle LPL overexpression and fasting duration on FFA kinetics are unknown. Transgenic mice with muscle-specific LPL overexpression (MCKhLPL) and control mice (Con) were studied at rest during a 50-minute constant infusion of [9,10- 3H]palmitate to determine FFA kinetics after both 4 and 16 hours of fasting. FFA concentration was not different between groups after the 4-hour (Con, 0.80 +/- 0.06 mmol/L; MCKhLPL, 0.83 +/- 0.07 mmol/L) and 16-hour (Con, 0.83 +/- 0.04 mmol/L; MCKhLPL, 0.80 +/- 0.07 mmol/L) fast. FFA turnover (Ra) was not significantly different between MCKhLPL and Con groups after the 4-hour fast (Con Ra = 2.52 +/- 0.36 micromol/min; MCKhLPL Ra = 2.37 +/- 0.27 micromol/min). However, FFA turnover was significantly decreased after the 16-hour fast in MCKhLPL mice vs controls (Con Ra = 2.89 +/- 0.52 micromol/min; MCKhLPL Ra = 1.64 +/- 0.17 micromol/min; P < .05). The significantly lower FFA Ra in MCKhLPL vs control mice was due to a decrease in MCKhLPL FFA turnover from the 4- to 16-hour fast, whereas FFA turnover was unchanged in controls. The changes in FFA appearance after the 16-hour fast in MCKhLPL mice are most likely explained by increased reliance by skeletal muscle on plasma triglyceride as a fuel. These data suggest increased skeletal muscle LPL expression decreases dependence on plasma FFA during prolonged fasting in mice.

Effect of impaired glucose uptake on postexercise glycogen repletion in skeletal muscles of insulin-treated streptozotocin-diabetic fasted rats.

During recovery from intense exercise performed while fasting, the replenishment of muscle glycogen stores from glucose requires the activation of glucose transport. This study examines if insulin-treated streptozotocin (STZ) diabetes in rats impairs the rate of muscle glucose utilization and glycogen repletion when no food is ingested during recovery from high-intensity exercise. Rats fasted for 24 hours were injected with high doses of STZ (150 mg/kg) to cause severe diabetes, and their glycemia was normalized for 10 days with twice-daily insulin injections. High-intensity exercise in these rats resulted in a marked increase in plasma glucose, which remained higher than preexercise levels thereafter, whereas in control animals, the rise in glycemia was only of a short duration. During recovery, the rates of 2-deoxy-[(3)H]glucose utilization in muscles rich in fast twitch red fibers (red and mixed gastrocnemius muscles) were much lower in STZ-diabetic than in control rats, but were not affected by diabetes in muscles comprised mainly of fast twitch white fibers (white gastrocnemius muscle). Despite these effects on glucose utilization, STZ diabetes had no inhibitory effect on the rate and extent of glycogen deposition and fractional velocities of glycogen synthase across all muscles. In conclusion, although insulin-treated STZ diabetes in fasted rats inhibits glucose transport rates in fast twitch red muscle fibers post-intense exercise, this has no effect on muscle glycogen repletion either because glucose transport does not control the rate of glycogen synthesis or because of a compensatory increase in the activity of lactate glyconeogenesis in these muscles.

Post-exercise muscle glycogen repletion in the extreme: effect of food absence and active recovery.

Glycogen plays a major role in supporting the energy demands of skeletal muscles during high intensity exercise. Despite its importance, the amount of glycogen stored in skeletal muscles is so small that a large fraction of it can be depleted in response to a single bout of high intensity exercise. For this reason, it is generally recommended to ingest food after exercise to replenish rapidly muscle glycogen stores, otherwise one's ability to engage in high intensity activity might be compromised. But what if food is not available? It is now well established that, even in the absence of food intake, skeletal muscles have the capacity to replenish some of their glycogen at the expense of endogenous carbon sources such as lactate. This is facilitated, in part, by the transient dephosphorylation-mediated activation of glycogen synthase and inhibition of glycogen phosphorylase. There is also evidence that muscle glycogen synthesis occurs even under conditions conducive to an increased oxidation of lactate post-exercise, such as during active recovery from high intensity exercise. Indeed, although during active recovery glycogen resynthesis is impaired in skeletal muscle as a whole because of increased lactate oxidation, muscle glycogen stores are replenished in Type IIa and IIb fibers while being broken down in Type I fibers of active muscles. This unique ability of Type II fibers to replenish their glycogen stores during exercise should not come as a surprise given the advantages in maintaining adequate muscle glycogen stores in those fibers that play a major role in fight or flight responses. Key PointsEven in the absence of food intake, skeletal muscles have the capacity to replenish some of their glycogen at the expense of endogenous carbon sources such as lactate.During active recovery from exercise, skeletal muscles rich in type II fibers replenish part of their glycogen stores even in the absence of food intake.Post-exercise muscle glycogen synthesis in the fasted state is facilitated, in part, by the transient dephosphorylation-mediated activation of glycogen synthase and inhibition of glycogen phosphorylase.

The effect of midday moderate-intensity exercise on postexercise hypoglycemia risk in individuals with type 1 diabetes.

CONTEXT: Exercise increases the risk of hypoglycemia in type 1 diabetes. OBJECTIVE: Recently we reported a biphasic increase in glucose requirements to maintain euglycemia after late-afternoon exercise, suggesting a unique pattern of delayed risk for nocturnal hypoglycemia. This study examined whether this pattern of glucose requirements occurs if exercise is performed earlier in the day. DESIGN, PARTICIPANTS, AND INTERVENTION: Ten adolescents with type 1 diabetes underwent a hyperinsulinemic euglycemic glucose clamp on 2 different occasions during which they either rested or performed 45 minutes of moderate-intensity exercise at midday. Glucose was infused to maintain euglycemia for 17 hours after exercise. MAIN OUTCOME MEASURES: The glucose infusion rate (GIR) to maintain euglycemia, glucose rates of appearance and disappearance, and levels of counterregulatory hormones were compared between conditions. RESULTS: GIRs to maintain euglycemia were not significantly different between groups at baseline (9.8 ± 1.4 and 9.5 ± 1.6 g/h before the exercise and rest conditions, respectively) and did not change in the rest condition throughout the study. In contrast, GIR increased more than 3-fold during exercise (from 9.8 ± 1.4 to 30.6 ± 4.7 g/h), fell within the first hour of recovery, but remained elevated until 11 hours after exercise before returning to baseline levels. CONCLUSIONS: The pattern of glucose requirements to maintain euglycemia in response to moderate-intensity exercise performed at midday suggests that the risk of exercise-mediated hypoglycemia increases during and for several hours after moderate-intensity exercise, with no evidence of a biphasic pattern of postexercise risk of hypoglycemia.

A 10-s sprint performed after moderate-intensity exercise neither increases nor decreases the glucose requirement to prevent late-onset hypoglycemia in individuals with type 1 diabetes.

OBJECTIVE: To determine whether performing a 10-s sprint after moderate-intensity exercise increases the amount of carbohydrate required to maintain euglycemia and prevent late-onset postexercise hypoglycemia relative to moderate-intensity exercise alone. RESEARCH DESIGN AND METHODS: Seven individuals with type 1 diabetes underwent a hyperinsulinemic-euglycemic clamp and performed 30 min of moderate-intensity exercise on two separate occasions followed by either a 10-s maximal sprint effort or no sprint. During the following 8 h, glucose infusion rate to maintain euglycemia and rates of glucose appearance and disappearance were measured continuously. RESULTS: In response to exercise and throughout the 8-h recovery period, there were no differences in glucose infusion rate, blood glucose levels, plasma insulin concentrations, and rates of glucose appearance and disappearance between the two experimental conditions (P > 0.05). CONCLUSIONS: A 10-s sprint performed after 30 min of moderate-intensity exercise does not affect the amount of carbohydrate required to maintain euglycemia postexercise in individuals with type 1 diabetes.

Increased expression of the SNARE accessory protein Munc18c in lipid-mediated insulin resistance.

Fatty acids inhibit insulin-mediated glucose metabolism in skeletal muscle, an effect largely attributed to defects in insulin-mediated glucose transport. Insulin-resistant mice transgenic for the overexpression of lipoprotein lipase (LPL) in skeletal muscle were used to examine the molecular mechanism(s) in more detail. Using DNA gene chip array technology, and confirmation by RT-PCR and Western analysis, increases in the yeast Sec1p homolog Munc18c mRNA and protein were found in the gastrocnemius muscle of transgenic mice, but not other tissues. Munc18c has been previously demonstrated to impair insulin-mediated glucose transport in mammalian cells in vitro. Of interest, stably transfected C2C12 cells overexpressing LPL not only demonstrated increases in Munc18c mRNA and protein but also in transcription rates of the Munc18c gene. To confirm the relevance of fatty acid metabolism and insulin resistance to the expression of Munc18c in vivo, a 2-fold increase in Munc18c protein was demonstrated in mice fed a high-fat diet for 4 weeks. Together, these data are the first to implicate in vivo increases in Munc18c as a potential contributing mechanism to fatty acid-induced insulin resistance.