brooks ch 9 p181-191;197-201 –some small sections already covered outline maintenance of blood...
TRANSCRIPT
• 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
• 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