Glucoregulation During and After Exercise Kaitlin Deason and

Glucoregulation During and After Exercise Kaitlin Deason and Confidential Group Members FCS 607

Overview • Normal glucose metabolism vs. endurance glucose metabolism • Glucose needs for the endurance athlete • Review of current literature Men Vs. Women and Glucoregulation High sugar food and endurance exercise Exercise vs. Calorie restriction & Glucoregulation • Diabetes and Glucoregulation • Future Research

Why is Glucose Regulation Important? • Glucose is essential fuel for the brain • Prolonged hypoglycemia can lead to brain death • Major source of energy formation through the TCA cycle and hexose-monophosphate shunt

Regulation of Glucose 1. Metabolic or allosteric • Phosphorylation of glucose § • Fig. 15. 7 The Cori Cycle. Glucose uptake by GLUT 2 Cori Cycle 2. Hormonal • • • Insulin Glucagon Epinepherine Growth Hormone And more…. Boyer, R. (2002). Concepts in biochemistry. Toronto, Canada: John Wiley and Sons, Inc.

Hormone Regulation of Glucose Table 20. 2 Biochemical actions of major hormones Boyer, R. (2002). Concepts in biochemistry. Toronto, Canada: John Wiley and Sons, Inc.

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Glucose and Exercise • Carbohydrates, specifically glucose, are the primary fuel during exercise above 65% VO 2 max • Energy during exercise is largely dependent on glycogen stores ▫ Remember: muscle glycogen is largest store of glycogen in the body followed by liver glycogen ▫ Liver: 75 -100 g of glycogen can deplete in 18 -24 hrs ▫ Muscles: 300 -400 g of glycogen • Also relies on blood glucose ▫ ~25 g of glucose

Fuel for Different Types of Exercise Table 20. 4 Biochemical characteristics of sprinting and endurance running Boyer, R. (2002). Concepts in biochemistry. Toronto, Canada: John Wiley and Sons, Inc.

Carbohydrate Recommendations for Endurance Athletes • Daily recommended intake: § 7 -10 g CHO/kg § Ultraendurance athletes may need more than 11 g/kg • Recommended intake prior to exercise: § 3 hours prior: 3 g/kg § 2 hours prior: 2 g/kg § 1 hour prior: 1 g/kg • Recommended intake during exercise: § 30 -60 g per hour of exercise • Recommended intake post exercise: § 1. 5 g/kg immediately following exercise (within 30 minutes) plus another 1. 5 g/kg 2 hours later

Utilization of Glucose During Exercise • At rest: § Glucose primarily used for brain and CNS § >20% of glucose is being used by the muscles § Glycogen stores are full • During endurance exercise: § Muscle glucose uptake increases. § Initially- Liver produces glucose from glycogen (glycogenolysis) § As exercise continues- Glycogen stores decrease and more glucose is produced from gluconeogenesis

Glycogen Repletion Following Exercise • Used to restore blood glucose levels back to normal range • Glucose consumed immediately following exercise promotes muscle uptake of glucose to replete glycogen stores (glycogenesis). • More effective immediately following exercise because: 1. Blood flow to muscles is increased 2. The muscle cells are more sensitive to effects of insulin which promotes glycogen storage 3. Muscle cells more likely to uptake glucose

http: //www. elmhurst. edu/~chm/vchembook/604 glycogenesis. html

Hypoglycemia vs. Hyperglycemia Hypoglycemia • Low glucose in the blood • Lower than 70 mg/d. L • Causes: ▫ Too much circulating insulin ▫ Lack of food ▫ Missed meals or snacks ▫ Increased exercise or strenuous activity ▫ Alcohol intake without food • Symptoms: ▫ Intense Hunger ▫ Sweating ▫ Trembling ▫ Weakness Hyperglycemia • Excessive glucose in the blood • Higher than 180 mg/d. L • Causes: ▫ Too little insulin production ▫ Insulin resistance ▫ Increased food intake • Symptoms: ▫ Polyuria ▫ Polydipsia ▫ Weight loss ▫ Fatigue ▫ Electrolyte disturbances

Men vs. Women: Previous Regulatory Studies Found: Men Women • Lipolysis (not elevated, not depressed) • Free fatty acid (FFA) mobilization (slight elevation) • Lipid oxidation (slight elevation) • Free fatty acid (FFA) mobilization • Lipid oxidation

Glucoregulation is More Precise in Women Than in Men During Postexercise Recovery • Objective: Determine the rates of glucose appearance (Ra), disappearance (Rd), and metabolic clearance (MCR) before, during, and after isoenergetic moderate and hardintensity exercise. • Design: 10 men and 8 women ▫ Received continuous infusion of glucose tracer to measure glucose kinetics. ▫ Studied under 3 different conditions with diet unchanged between trials Henderson, Fattor, Horning, Faghihnia, Johson, et. al, 2008.

Rate of Glucose Appearance (Ra) Glucose Ra significantly decreased in both sexes in trial C (65% VO ₂ peak)

Rate of Glucose Disappearance (Rd) Glucose Rd significantly decreased in both sexes in trial C (65% VO ₂ peak)

Rate of Metabolic Clearance (MCR) Glucose MCR significantly decreased in both sexes in trial C (65% VO ₂ peak)

Summary Men (n= 10) Time and Trial Preexercise, pooled Ra Rd Women (n= 8) MCR Ra Rd MCR 3. 1 +/- 0. 2 3. 6 +/- 0. 3 4. 0 +/- 0. 3 Exercise 45% 6. 4 +/- 0. 4 6. 5 +/- 0. 4 8. 7 +/- 0. 6 5. 4 +/- 0. 4 5. 3 +/- 0. 4 6. 7 +/- 0. 7 65% 9. 0 +/- 0. 6 9. 2 +/- 0. 6 12. 7 +/1. 0 8. 6 +/- 1. 0 8. 5 +/- 0. 9 11. 1+/-1. 4 Recovery Control 2. 4 +/- 0. 1 2. 8 +/- 0. 1 2. 4 +/- 0. 1 2. 9+/- 0. 1 45% 2. 8+/- 0. 1 2. 7 +/- 0. 2 3. 5 +/- 0. 2 2. 4 +/- 0. 1 3. 0 +/- 0. 2 65% 3. 1 +/- 0. 2 3. 8 +/- 0. 2 2. 6 +/- 0. 2 2. 7 +/- 0. 2 3. 3 +/- 0. 2

Men vs. Women Conclusion • Women have a greater capacity for lipid oxidation which correlates to the lower glucose Ra, Rd, MCR • Women are able to regain control over glycemic levels and glucose flux more rapidly in recovery than men

Glucoregulation, Exercise and Endothelial Cells? • Regular physical activity is linked to a decreased risk of cardiovascular disease. • Part of the benefit may be due to exercise induced improvements in endothelial function. • After meal (postprandial) glycemia is reduced by exercise that was performed hours to days earlier • It inconceivable that acute endurance exercise minimizes the postprandial impairment in endothelial function.

Endothelial Function After High-Sugar Food Ingestion Improves with Endurance Exercise Performed on the Previous Day Objective Design • Determine whether endurance exercise performed 17 hours before a high-sugar food ingestion attenuates postprandial impairment in endothelial function. • 13 men and women (48 +/17 years) were studied on two occasions: ▫ 48 hours after a 60 minute endurance exercise (control) ▫ 17 hours after a 60 minute endurance exercise • Brachial artery flow mediated dilation (FMD) was used to assess endothelial function before and after the ingestion of a candy bar (Snickers) and soft drink (Sprite). Weiss, Arif, Villareal, Marzetti, & Holloszy, 2008

Summary Glucose (a) and insulin (b) response to a candy bar and soft drink 17 hours (exercise) and 48 hours (control) after endurance exercise

Summary Time dependent changes in the diameter (a) and endothelial function (b) of the brachial artery in response to ingestion of candy bar and soft drink 17 hours (exercise) and 48 hours (control) after endurance exercise.

Summary Endothelial function improved after a high-sugar food ingestion by a single bout of exercise performed 17 hours before testing. This improvement is correlated to the glucoregulation induced by exercise

Conclusion “Acute endurance exercise The study supports this enhances glucoregulation and hypothesis because: “exercise reduces postprandial induced improvement in glycemia. ” postprandial endothelial function was accompanied by significant reductions in plasma glucose and insulin concentrations. ”

Improvements in Glucose Tolerance and Insulin Action Induced by Increasing Energy Expenditure or Decreasing Energy Intake • Objective: To determine that improvements in glucoregulation and insulin action are directly attributed to weight loss through exercise-induce energy expenditure, compared to weight loss through calorie restriction. • Participants: Sedentary men and women, ages 50 -60 y. o. , with a BMI of 23. 5 -29. 9 (considered overweight, not obese)

Study Design • 1 year • Exercise energy expenditure – n = 18 ▫ Increase energy expenditure by 16% first 3 months and 20% for the following 9 months • Calorie restriction – n = 18 ▫ Decrease calorie intake by 16% during first 3 months and 20% remaining 9 months • Healthy lifestyle – n = 10 (control group) ▫ Did not receive instructions to change diet or exercise behaviors. If requested, could have dietary counseling and were offered yoga classes

Testing • Oral-Glucose-Tolerance Test & Fast Blood Collection ▫ Two-hour, 75 g, OGTT ▫ Performed at baseline and at end of intervention • Body weight and composition • Energy Intake • Aerobic capacity • Physical activity levels

Results • Both groups – Exercise expenditure • and calorie restriction – resulted in • significant improvements in glucose tolerance & insulin action • Surprisingly, there was no difference between groups as what was originally hypothesized

Results - Explained • There was a decrease in body fat – more specifically, abdominal fat, which is a main factor in insulin improvements. Not significantly different between the two groups. • Different mechanisms for insulin improvements in both groups. • Calorie restriction-specific skeletal muscle adaptation has been shown to augment insulin-stimulated glucose transport in a different manner than exercise training-specific mechanism. • Determined that calorie-restriction and exercise training are additive effects

Conclusion • While exercise and calorie restriction are effective methods in reducing the incidence of T 2 DM, more research must be done on the independent effects of both methods. • Both can greatly improve glucose tolerance and insulin action in non-obese, healthy, middle aged men and women.

Diabetes Management/Prevention & Exercise • Exercise is one of the most important factors in managing and/or preventing diabetes • Benefits – ▫ ▫ Reduced cardiovascular risk factors Maintain healthy weight Reduce body fat Enhance wellness

Type I Diabetes • Exercise should be carefully integrated into diabetes management plan, as this type of diabetes lacks the metabolic adjustments needed to maintain fuel homeostasis during exercise. • Must be able to maintain optimal blood glucose levels during exercise • Insulin adjustments & carbohydrate supplements can be used to maintain optimal blood glucose levels

Direct Effects of Exercise on Blood Glucose Levels in T 1 DM • • Level of training and fitness Intensity & duration of exercise Time & type of exercise Metabolic control Nutrition status Glycogen stores Circulating insulin levels

Endurance Athletes & T 1 DM • Use carbohydrate supplements (sport drinks, diluted juices, sport bars, sport jelly beans) conservatively • Refrain from taking extra insulin when CHO is consumed during exercise for the purpose of maintaining proper blood glucose levels • Extra CHO may be needed post-exercise due to increased insulin sensitivity and glycogen synthesis

Physiological Benefits of Exercise for Type II Diabetes • • Increases peripheral insulin sensitivity Reduction of insulin requirements Decreased plasma insulin levels Improves glucose tolerance Help improve glycemic control in T 2 DM Normalize glucose homeostasis in pre-diabetics Lower blood pressure Increased lipid profile

Exercise Training-Induced Improvements in Insulin Action • Single bout of exercise increases skeletal muscle glucose uptake through a separate insulindependent mechanism that is completely different than the typical insulin signaling defects in diabetics • Found that this “sensitive insulin” effect is short lived and disappears within about 48 hours • Conversely, repeated physical exercise results in an increase in skeletal muscle insulin action in insulin-resistance and obese individuals

Why the difference? • This has been found to occur due to the increased expression and/or key signaling activity of proteins associated with muscle glucose uptake and metabolism in skeletal muscle (AMP-activated protein kinase (AMPK) & protein kinase B substrate – AS 160) • Lipid oxidation has been found to be another mechanism which increases and improves insulin sensitivity (weight loss)

Pre/During/Post-Exercise Nutrition Suggestions • Pre-Exercise – 30 min (must be easily digested and absorbed to provide immediate energy) ▫ Small piece of fruit ▫ Gatorade ▫ 100% fruit juice ▫ ½ Sports bar • During Exercise ▫ Sport Jelly Beans ▫ Sports drink ▫ Gu ▫ Sports bar ▫ Fruit • Post-Exercise (must be within 30 -45 min of finishing exercise) ▫ Chocolate Milk ▫ Piece of fruit with cottage cheese ▫ ½ Turkey Sandwich on Whole Wheat bread ▫ Graham crackers with peanut butter ▫ Fruit smoothie with low-fat yogurt

Future Research • More research needs to be done on precise methods for glucoregulation during and post-exercise in diabetics – signaling proteins and the physiological/biological mechanisms behind skeletal muscle glucose uptake? • More research on GLUT 4? GLUT 4 is the insulinregulated glucose transporter for adipose and muscle tissue. • Improve insulin resistance before the onset of T 2 DM? • Research varies on pre/during/post-workout nutrition and how much is appropriate for the specific exercise

References • Boyer, R. (2002). Concepts in biochemistry. Toronto, Canada: John Wiley and Sons, Inc. • Dunford, M. (Ed. ). (2006). Sports nutrition: A practice manual for professionals. Chicago, Illinois: American Dietetic Association. • Hawley, J. A. , and Lessard, S. J. (2008). Exercise training-induced improvements in insulin action. Acta Physiologica, 192(1) 127 -135. • Henderson, G. , Fattor, J. , Horning, M. , Faghihnia, N. , Johnson, M. , et al. (2008). Glucoregulation is more precise in women than in men during postexercise recovery. American Journal of Clinical Nutrition, 87 (6), 1686 -1694.

References • Mahan, K. L. & Escott-Stump, S. (2008). Krause’s Food & Nutrition Therapy. St. Louis, MI: Saunders Elsevier. • Weiss, E. , Arif, H. , Villareal, D. , Marzetti, E. , & Holloszy, J. (2008). Endothelial function after high sugar-food ingestion improves with endurance exercise performed on the previous day. American Journal of Clinical Nutrition, 88(1), 51 -57. • Weiss, E. , Racette, S. , Villareal, D. , Fontana, L. , Steger-May, K. , Schechtman, K. , Klein, S. , Holloszy, J. (2006). Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. American Journal of Clinical Nutrition, 84, 1033 -42.