Block 3Lecture 33 Flashcards

1
Q

what are the 2 critical stages of regulation for glucose by skeletal muscle

A
  1. vascular delivery of blood glucose

2. transmembrane transport of glucose

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2
Q

what is glucose metabolism based on

A

energetic needs and endocrine status

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3
Q

how does skeletal muscle receive blood

A

via systemic circulation

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4
Q

how the tissue receives blood depends on what?

A
  1. cardiac output
  2. vascular resistance
  3. capillary density
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5
Q

what is vascular resistance

A

degree of vasodilation in vascular bed supplying tissue

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6
Q

what is capillary density

A

number of capillary contacts to the skeletal muscle

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7
Q

what happens in insulin mediated dilation

A

insulin acts on endothelial cells in arteries to activate eNOS causing synthesis of NO which causes relaxation of cells and vasodilation to promote glucose delivery to skeletal muscle

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8
Q

what mechanisms does insulin mediated dilation use

A

increased capillary recruitment and greater capillary surface area

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9
Q

where are insulin receptors located in myocytes

A

in the sarcolemmal membrane

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10
Q

what is the main glucose transporter under insulin-mediated conditions

A

GLUT4

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11
Q

what type of receptor is the insulin receptor

A

a receptor tyrosine kinase, a major type of catalytic receptor

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12
Q

describe the structure of the insulin receptor

A
  • it is a heterotetramer
  • consists of 2 extracellular a-subunits that bind the hormone
  • and 2 transmembrane beta subunits that have tyrosine kinase domains on the cytosolic side
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13
Q

what are the a and beta subunits joined by in the insulin receptor

A

sulfhydryl bonds

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14
Q

where does insulin bind on the insulin receptor

A

the cysteine rich domains of the a subunits thereby enhancing tyrosine kinase activity of the beta subunits

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15
Q

What is a primary substrate for activated insulin receptor tyrosine kinase

A

insulin receptor substance (IRS)

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16
Q

what are the major isoforms of IRS in skeletal muscle

A

IRS1 and IRS2

17
Q

what are the effects of activated insulin receptor and IRS

A

stimulation of glucose transport, enhances glucose storage as glycogen, increased protein synthesis, decreased protein breakdown, unregulation of lipid synthesis, and alterations in the expression of genes in the nucleus

18
Q

what is IRS1 and what can it do when phosphorylated

A

it is a docking protein, that can interact with effector proteins that possess SH2 domains

19
Q

what can PI3K interact with

A

dock with tyrosine phosphorylated IRS1 and SH2 domains

20
Q

what does PI3K do

A

produces signals that causes intracellular vesicles containing GLUT4 to fuse into sarcolemmal membrane

21
Q

explain the IRS-1/PI3K/AKt pathway in full

A

insulin binds to insulin receptor which signals IRS-1 to get phosphorylated, then it binds to effector proteins with SH2 domains, then PI3K can interact with this complex, the activation of this leads to fusion of vesicles containing GLUT4 to fuse into the membrane so the myocyte can transport glucose through facilitated diffusion

22
Q

what happens when the insulin disengages from the insulin receptor

A

tyrosine phosphatase dephosphorylate tyrosine residues on IRS-1

23
Q

what is the location and Km for GLUT1

A

location- almost all tissues

Km- about 3mM

24
Q

what is the location and Km for GLUT2

A

location- basolateral membrane of liver, pancreatic beta cells (in rodents not humans), intestine and kidney
Km- 17mM

25
Q

what is the location and Km for GLUT3

A

location- neuronal cells, placenta

Km- 1.4 mM

26
Q

what is the location and Km for GLUT4

A

location- skeletal and cardiac muscle, adipocytes, specific hypothalamic neurons
Km- about 5mM

27
Q

why is GLUT4 appropriate in skeletal muscle

A

because of its high affinity for substrate

28
Q

why is GLUT2 in the liver

A

because it is an isoform not easily saturated under essentially all physiological conditions primarily involved in glucose homeostasis because the glucose concentration around the hepatocyte is high the saturability needs to be high

29
Q

why is glucose transport and glucose blood concentration proportional in liver cells?

A

because there are so many transporters a double in blood glucose can be transported into the membrane at the same rate the blood glucose levels increase

30
Q

Why must GLUT2 have a low affinity for glucose

A

so it can respond to increases in glucose concentration with matching increases in insulin secretion

31
Q

why is it important that humans have beta cells with GLUT1?

A

the cells need to be able to couple increases in blood glucose with appropriate increases in insulin secretion