• 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

• 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

• 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

• 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

Fasting State fig 5-3b

• 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

• 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

• 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

• 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

• 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

• 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

• 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