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Skeletal Muscle Glucose Uptake During Exercise: How Is It Regulated

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Title: Skeletal Muscle Glucose Uptake During Exercise: How Is It Regulated


1
Skeletal Muscle Glucose Uptake During Exercise
How Is It Regulated?
  • Adam J. Rose and Erik A. Richter
  • Presented by Daniel Beteck

2
Some Important Terms
  • Glucose Transporters (GLUT) are a family of
    membrane proteins found in most mammalian cells
  • GLUT4 is an insulin-regulating glucose
    transporter found in adipose tissues and striated
    muscle (skeletal and cadiac). It is responsible
    for insulin-regulated glucose disposal.
  • AMP-activated protein kinase or AMPK is an enzyme
    that plays a role in monitoring energy use within
    a cell.
  • Protein Kinase C is an enzyme that contains 10
    isoforms. The PKC containing ?,?I, ?II isoforms
    reruires Ca2, diacylglycerol (DAG), and a
    phosholipid like phosphatidylcholine for it to be
    activated.
  • Hexokinase is an enzyme that phosphorylates
    glucose to glucose-6-phosphate (G6P) during
    glycolysis.

3
Some Important Terms
  • Glycogenolysis is the catabolism of glycogen by
    removing a glucose monomer and adding a phosphate
    group to produce glucose-1-phosphate.
  • - Glucose-1-phosphate is then converted to
    Glucose-6-phosphate .
  • - Glycogenolysis is stimulated by the hormones
    glucagon and epinephrine.
  • Phosphorylation is the addition of a phosphate
    (PO4) group to an organic molecule

4
IntroductionWhat Happens During Exercise?
  • Rate of contracting skeletal muscle glucose
    uptake increases substantially
  • Amount of glucose taken up depends on exercise
    intensity and duration
  • Catabolism of carbohydrates and fatty acids cause
    an increase in turnover of ATP
  • Blood glucose concentrations can be reduced in
    people with type II diabetes
  • In post absorptive state, blood glucose
    contributes to ATP resynthesis

5
Introduction

6
Skeletal Muscle
7
Skeletal Muscle
  • Skeletal Muscle is a striated muscle attached to
    skeleton for movement
  • There are two types of fibers for skeletal
    muscles Type I and Type II
  • - Type I fibers are good for endurance and are
    slow to tire because they use oxidative
    metabolism
  • - Type II fibers are used for short bursts of
    speed and power, use anaerobic metabolism, and
    are therefore quicker to tire.
  • Skeletal muscle cells are stimulated by
    acetylcholine, which is released at neuromuscular
    junctions by motor neurons
  • After stimulation their sarcoplasmic reticulums
    release ionic calcium (Ca2), that interacts with
    the myofibrils and induces muscular contraction
    by the sliding filament mechanism.

8
Sites of Glucose Uptake Regulation
  • 3 sites of skeletal glucosse uptake regulation
  • Glucose delivery to skeletal muscle cells
  • Glucose transport due to surface membrane
    permeability
  • Glucose flux via intracellular metabolism

9
Glucose Uptake Regulation During Exercise
  • Glucose delivery to skeletal muscle cell
  • - Expressed as a product of blood flow and blood
    concentration
  • - Increase in muscle perfusion due to blood flow
    increase is important for the rate of glucose
    uptake during contractions
  • - Change in blood glucose concentration during
    exercise is proportional to change in glucose
    uptake by s.muscle
  • - During exercise blood glucose concentration is
    an important rate limiting factor for glucose
    uptake

10
Glucose Uptake Regulation During Exercise
11
Glucose Uptake Regulation During Exercise
  • Glucose transport during exercise
  • GLUT4 is most important glucose transporter
    during exercise
  • Insulin induces the redistribution of GLUT4 from
    skeletal muscle cell to the plasma membrane.
  • When on the surface, GLUT4 facilitates the
    passive diffusion of blood glucose down its
    concentration gradiant into skeletal muscle.
  • Glucose transport is rate limiting for glucose
    uptake in skeletal muscle

12
Glucose Uptake Regulation During Exercise
13
Glucose Uptake Regulation During Exercise
  • Glucose uptake metabolism in skeletal muscle
  • After GLUT4 transport of glucose, glucose is
    phosphorylated quickly by hexokinase to form
    glucose-6-phosphate
  • G6P enters glycolysis after glucose
    phosphorylation by HK.
  • G6P also serves to maintain the concentration
    gradient for glucose to passively enter cells
    because it cannot diffuse out of the cell
  • Role of HK in regulation of glucose uptake during
    exercise is probably limiting to glucose uptake
    during intense exercise when accumulated G6P
    inhibits HK activity

14
Glucose Uptake Regulation During Exercise
  • To summarise
  • The regulation of skeletal muscle glucose uptake
    during exercise is regulated by the mechanisms of
  • Glucose supply
  • Perfusion
  • Blood glucose concentration
  • Glucose transport
  • Surface membrane
  • Glucose gradient
  • GLUT activity
  • Glucose phosphorylation
  • HK activity
  • Substrate flux

15
Regulation of S.Muscle Glucose Transport by
Exercise/Contraction
  • Not enough information on whether
    exercise/contraction regulates skeletal muscle
    glucose transport
  • Activation of CAMK isoforms during
    exercise/contraction to regulate skeletal muscle
    glucose transport is regarded as a feedforward
    level of regulation
  • Because AMPK is activated when muscle energy is
    low, AMPK activity is regarded as a feedback
    level of regulation
  • aPKC activity is higher with insulin and
    exercise/contraction

16
Physiological Importance
  • Exercise increases skeletal muscle glucose uptake
    and GLUT translocation in people with type II
    diabetes
  • This mechanism is important as an alternative
    pathway to increase glucose disposal in skeletal
    muscle in states of insulin resistance
  • AMPK skeletal muscle stimulating drugs like
    metformin and rosiglitazone are being used to
    treat diabetes
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