1. Brooks ch 9 p181-191;197-201 –Some small sections already covered Outline Maintenance of Blood Glucose during exercise –Feed forward Control - SNS –Feed back Control - ratio of insulin / glucagon –Control of Gluconeogenesis - Ca++, cAMP Neural - Endocrine Control

2. During exercise, the maintenance of homeostatic levels is important, particularly blood glucose Blood glucose is maintained at 4-5.5 mM (90- 100mg/dl) Fig 5.5 Neural - Endocrine Control

3. During exercise glucose uptake into muscle is stimulated in order to maintain ATP homeostasis Blood glucose is maintained through release from the liver and kidneys and the mobilization of alternate fuels Response to maintain blood glucose is governed by the endocrine system and the Sympathetic NS –Via feed-forward and feed-back control mechanisms Glucose homeostasis is important for CNS metabolism and the anaplerotic effect of carbohydrates on fat metabolism Neural - Endocrine Control

4. Several ways to increase blood glucose –Release from gut (prior meal) –Release from glycogen stores –Gluconeogenesis - production of glucose from precursors in kidney and liver - lactate, pyruvate, glycerol, alanine Body also raises levels of alternative substrates and delivers them to active tissue –fatty acids, TG, lactate, leucine –Which serve to spare glucose use and postpone hypoglycemia and fatigue Growth Hormone and Catecholamines mobilize FFA and TG Glucose Appearance

5. Fasting State fig 5-3b

6. During exercise the rise in glucose uptake is primarily in the active tissue beds Fig 9-2 the addition of arm exercise, further increases whole body uptake but blood glucose rises due to high Hepatic Glucose Production (HGP) stimulated by increased catecholamines and decreased insulin (fig 9-3) This is a feed forward response, as blood glucose did not drop Feed forward Control

8. Liver is essential to the regulation of blood glucose –Uptake and storage when levels are high –Release when levels are low Uptake and Release are driven by [ ] gradients –In and Out through high Km GLUT 2 (20mM) Insulin stimulates glucokinase synthesis which phophorylates glucose preventing its efflux and keeping the [ ] gradient high - glucose then stored or metabolized When there is a fall in [glucose] in liver –Activity of GK (also known as high Km HK) falls –Activity of G6Pase inc, forming glucose for release Role of the Liver

9. Storage of glycogen is limited to 5-6% of liver by weight (5g/100g) As G6P builds up in the liver during the fed state, it stimulates glycolysis and formation of acetyl-Co-A, then FFA and the synthesis of TG –TG packaged into VLDL and circulated to adipose Low insulin and blood glucose in fasting state stimulates FFA release and a decrease in glycolysis through glucose-fatty acid cycle (discussed earlier) –Acetyl co A inhibits PDH –Citrate inhibits PFK –G6P inhibits HK and glucose uptake (skeletal ms) Energy Storage

10. Insulin falls during exercise - likely due to rise in epinephrine (both changes result in increased HGP) With aerobic training –Decreased release of glucagon and catecholamines and an reduction in the fall in insulin at a given relative intensity –Fig 9-7 Insulin and exercise

11. Glucagon enhances glycogenolysis (glycogen breakdown) and gluconeogenesis through adenylate cyclase Alanine released from muscle after prolonged exercise also stimulates glucagon –Increases amino acid uptake for gluconeogenesis Glucagon response to exercise is also dampened with training - Fig 9-8 Glucagon

12. Glucose produced from lactate, pyruvate or alanine through the use of bypass steps for the irreversible steps of Glycolysis Pyruvate carboxylase (PC) and Phophoenolpyruvate carboxylase (PEPCK) reverse PK through Malate shuttle - Fig 9-15 Fructose-1,6-Bisphosphatase reverses PFK Glucose 6 Phosphatase reverses HK (GK) These enzymes are mainly found only in liver and kidneys Gluconeogenesis in Liver

14. cAMP and Calcium thought to play important roles in stimulation of gluconeogenesis PK-L liver type PK can be phosphorylated and inhibited by Ca++ and cAMP dependant protein kinases –This will inhibit glycolysis and favour glucose release Fructose 2,6 Bisphosphate (present after eating) will activate glycolysis and inhibit gluconeogenesis –Activates PFK- and inhibits F 1,6 BPase PFK-2 in liver can act as either kinase or phosphatase (reverse) –cAMP dependant protein kinase will inhibit PFK-2 kinase function and activate PFK-2 phoshorylase function Control of Gluconeogenesis