Down Regulation & Insulin Resistance?

Main Page | Report this Page

Science Forum Index » Immunology Forum » Down Regulation & Insulin Resistance?

Page 1 of 2 Goto page 1, 2 Next

Author

Message

Kumar

Posted: Fri Mar 14, 2008 9:19 pm

Guest

Hello,

Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty. In such consideration, why increased insulin's exposure
( natural or medicated) to target cells, which can be common in type2
people, address one mechanism for getting insulin's resistance and
hyperglycemia in type2 diabetes?

"Downregulation
Downregulation is the process by which a cell decreases the number of
a cellular component, such as RNA or protein, in response to an
external variable. An increase of component is called upregulation.

For example, the cell decreases the number of receptors to a given
hormone or neurotransmitter to reduce its sensitivity to this
molecule. This is a locally acting negative feedback mechanism.

[edit] Receptor downregulation

[edit] Mechanism
For insulin, the process of downregulation occurs when there are
elevated levels of the hormone in the blood. When insulin binds to its
receptors on the surface of a cell, endocytosis of the hormone
receptor complex is initiated, only to be subsequently attacked by
intracellular lysosomal enzymes. The internalization is multi-
purposed, as it provides the pathway for degradation of the hormone
and also a way to regulate the number of sites that are available for
binding on the cell¢s surface. At high plasma concentrations, the
number of surface receptors for insulin is gradually reduced by the
accelerated rate of receptor internalization and degradation brought
about by increased hormonal binding. The rate of synthesis of new
receptors within the endoplasmic reticulum and their insertion in the
plasma membrane do not keep pace with their rate of destruction. Over
time, this self-induced loss of target cell receptors for insulin
reduces the target cell¢s sensitivity to the elevated hormone
concentration. The process of decreasing the number of receptor sites
is virtually the same for all hormones; it only varies in the receptor
hormone complex.

[edit] Cases
To illustrate this process we shall look at the insulin receptor sites
on the target cells of a type 2 diabetic. Due to the elevated levels
of blood glucose from excessive feeding in an overweight individual,
the â-cells (islets of Langerhans) in the pancreas must release more
insulin than normally emitted to match the demand and return the blood
to homeostatic levels. The near-constant increase in blood insulin
levels results from an effort to match the increase in blood glucose,
which will cause receptor sites on the person¢s cell to downregulate
and decrease the number of receptors for insulin, increasing the
subject¢s resistance by decreasing sensitivity to this hormone. There
is also a hepatic decrease in sensitivity to insulin. This can be seen
in the continuing gluconeogenesis in the liver even when blood glucose
levels are elevated. This is the more common process of insulin
resistance, which in turn leads to adult onset diabetes in that
subject. Other cases include Diabetes insipidus; here the kidneys
become insensitive to arginine vasopressin.

[edit] Reversal
There are ways to counteract this process; using the previous example
a type 2 diabetic may increase their sensitivity to insulin through
proper diet and regular exercise producing weight loss; some may even
return to their pre-diabetic state following this regimen."
http://en.wikipedia.org/wiki/Downregulation

Kumar

Posted: Sat Mar 15, 2008 12:45 am

Guest

On Mar 15, 2:31 pm, "Anja Lange" <anja.lae...@gmx.de> wrote:

Quote:

Kumar wrote:
Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.

If you understand german I recommend the following link to read some facts
and practical advice on that subject:http://www.chrostek.de/index.php/Curriculum/up%20und%20down%20Regulation

The concept is used in insulin pump therapy but the mechanism applies to
all.

Anja

Thanks but sorry I don't understand german. Can you or other brief it
in english or provide an english link.

Anja Lange

Posted: Sat Mar 15, 2008 4:31 am

Guest

Kumar wrote:

Quote:

Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.

If you understand german I recommend the following link to read some facts
and practical advice on that subject:
http://www.chrostek.de/index.php/Curriculum/up%20und%20down%20Regulation

The concept is used in insulin pump therapy but the mechanism applies to
all.

Anja

Kumar

Posted: Thu Mar 20, 2008 10:06 pm

Guest

On Mar 21, 11:02 am, Marshall Price <d0213...@yahoo.com> wrote:

Quote:

Kumar wrote:
Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.
http://en.wikipedia.org/wiki/Downregulation

I disagree; the topic may be "important," but as it stands, it's a lousy
article.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Pls look at it;

http://www.childrenwithdiabetes.com/dteam/2008-03/d_0d_f3e.htm

I aso checked about possibility of such downregulation with Diabetics
UK. Why such downregulation of insulin's receptors can't happen and
adress one reason to so called insulin resistance esp. when other
hormones can cause downregulations of thir receptors?

Possible clues, which can indicate excessive exposures of insulin can
be;

1. IR commonly happens in type2 diabetics, naturally or medicated.
2. IR looks to be reversed in later stages of type2, probably, on
getting frank diabetes or when beta cells are really damaged due to
previous over burdens on them.
3. Obesity may also be linked to either increase insulins secretion or
its decreases use, still overexposed to target cells.

4. Irregular and over-eating & opting Sed. and modern lifestyle may be
resuting increased and irregular insulin's secretion & exposures.

Looks, real issues are predisposed or acquired excessive cravings to
eat, opting sed./modern lifestyles & chronic stressors in crowded
cities--pollutions, noise, lighting, crowdings etc.

Today, I looked at my daugter force feeding her 2 years old boy. Such
aided/forced or excessive feeding to kids can be common in most
mothers as a practice, misconception ot just sentiment-- love &
affection. Can't it cause an aquired habit to overeat and expose more
insulin to target cells and mediating diabetes2?

Do normal kids really need to be forced(aided? feeded, even when they
don't demand?

Kumar

Posted: Thu Mar 20, 2008 10:11 pm

Guest

On Mar 21, 11:04 am, Marshall Price <d0213...@yahoo.com> wrote:

Quote:

Kumar wrote:
On Mar 15, 2:31 pm, "Anja Lange" <anja.lae...@gmx.de> wrote:
Kumar wrote:
Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.
If you understand german I recommend the following link to read some facts
and practical advice on that subject:http://www.chrostek.de/index.php/Curriculum/up%20und%20down%20Regulation

The concept is used in insulin pump therapy but the mechanism applies to
all.

Anja

Thanks but sorry I don't understand german. Can you or other brief it
in english or provide an english link.

It's mainly about glucose transporters (GLUT).

--
Marshall Price of Miami
Known to Yahoo as d021317c- Hide quoted text -

- Show quoted text -

Sorry but GLUT4 are insulin-regulated glucose transporter.

Kumar

Posted: Thu Mar 20, 2008 10:38 pm

Guest

On Mar 21, 1:11 pm, Kumar <lordshiva5...@gmail.com> wrote:

Quote:

On Mar 21, 11:04 am, Marshall Price <d0213...@yahoo.com> wrote:

Kumar wrote:
On Mar 15, 2:31 pm, "Anja Lange" <anja.lae...@gmx.de> wrote:
Kumar wrote:
Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.
If you understand german I recommend the following link to read some facts
and practical advice on that subject:http://www.chrostek.de/index.php/Curriculum/up%20und%20down%20Regulation

The concept is used in insulin pump therapy but the mechanism applies to
all.

Anja

Thanks but sorry I don't understand german. Can you or other brief it
in english or provide an english link.

It's mainly about glucose transporters (GLUT).

--
Marshall Price of Miami
Known to Yahoo as d021317c- Hide quoted text -

- Show quoted text -

Sorry but GLUT4 are insulin-regulated glucose transporter.- Hide quoted text -

- Show quoted text -

Following quote also tells ;Insulin induces the redistribution of
GLUT4

"GLUT4 is the insulin-regulated glucose transporter found in adipose
tissues and striated muscle (skeletal and cardiac) that is responsible
for insulin-regulated glucose disposal.
[edit] Reaction to insulin
In the absence of insulin, GLUT4 is sequestered in the interior of
muscle and fat cells, within the lipid bilayer of vesicles.

Insulin induces the redistribution of GLUT4 from intracellular storage
sites to the plasma membrane." http://en.wikipedia.org/wiki/GLUT4

Kumar

Posted: Thu Mar 20, 2008 10:55 pm

Guest

On Mar 21, 1:11 pm, Kumar <lordshiva5...@gmail.com> wrote:

Quote:

Direct and indirect affects can be as under;

"Effect of insulin on glucose uptake and metabolism. Insulin binds to
its receptor (1) which in turn starts many protein activation cascades
(2). These include: translocation of Glut-4 transporter to the plasma
membrane and influx of glucose (3), glycogen synthesis (4), glycolysis
(5) and fatty acid synthesis (6).
http://en.wikipedia.org/wiki/Insulin_receptor "

Marshall Price

Posted: Fri Mar 21, 2008 1:02 am

Guest

Kumar wrote:

Quote:

Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.

http://en.wikipedia.org/wiki/Downregulation

I disagree; the topic may be "important," but as it stands, it's a lousy
article.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Marshall Price

Posted: Fri Mar 21, 2008 1:04 am

Guest

Kumar wrote:

Quote:

On Mar 15, 2:31 pm, "Anja Lange" <anja.lae...@gmx.de> wrote:
Kumar wrote:
Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.
If you understand german I recommend the following link to read some facts
and practical advice on that subject:http://www.chrostek.de/index.php/Curriculum/up%20und%20down%20Regulation

The concept is used in insulin pump therapy but the mechanism applies to
all.

Anja

Thanks but sorry I don't understand german. Can you or other brief it
in english or provide an english link.

It's mainly about glucose transporters (GLUT).

--
Marshall Price of Miami
Known to Yahoo as d021317c

Kumar

Posted: Sun Mar 23, 2008 3:51 am

Guest

On Mar 23, 6:38 pm, Marshall Price <d0213...@yahoo.com> wrote:

Quote:

Kumar wrote:
Today, I looked at my daughter force-feeding her 2-year-old boy. Such
aided/forced or excessive feeding to kids can be common in most
mothers as a practice, misconception or just sentiment-- love &
affection. Can't it cause an acquired habit to overeat and expose more
insulin to target cells and mediating diabetes2?

I'd say she needs help -- either a book or a psychiatrist! What she's
doing is a well known, serious problem.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Yes, but how it can be relevant to getting diabetes2 afterwords?

Marshall Price

Posted: Sun Mar 23, 2008 8:31 am

Guest

Kumar wrote:

Quote:

On Mar 21, 11:04 am, Marshall Price <d0213...@yahoo.com> wrote:
Kumar wrote:
On Mar 15, 2:31 pm, "Anja Lange" <anja.lae...@gmx.de> wrote:
Kumar wrote:
Following article is very important if valid. I tried to check it from
other reputed people in diabetes, who don't deny or agree on this
possibilty.
If you understand german I recommend the following link to read some facts
and practical advice on that subject:http://www.chrostek.de/index.php/Curriculum/up%20und%20down%20Regulation
The concept is used in insulin pump therapy but the mechanism applies to
all.
Anja
Thanks but sorry I don't understand german. Can you or other brief it
in english or provide an english link.
It's mainly about glucose transporters (GLUT).

Sorry but GLUT4 are insulin-regulated glucose transporter.

Righty-o.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Marshall Price

Posted: Sun Mar 23, 2008 8:38 am

Guest

Kumar wrote:

Quote:

Today, I looked at my daughter force-feeding her 2-year-old boy. Such
aided/forced or excessive feeding to kids can be common in most
mothers as a practice, misconception or just sentiment-- love &
affection. Can't it cause an acquired habit to overeat and expose more
insulin to target cells and mediating diabetes2?

I'd say she needs help -- either a book or a psychiatrist! What she's
doing is a well known, serious problem.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Nico Kadel-Garcia

Posted: Sun Mar 23, 2008 10:41 am

Guest

Marshall Price wrote:

Quote:

And it's irrelevant to Type 1 diabetes, and the causality of Type 2 and
obesity is often reversed: the Type 2 and high insulin levels trigger hunger,
and weight gain, exacerbating the diabetes. So force feeding infants is
something to worry about for plenty of other reasons, I'd consider the risk of
diabetes to be one of the least critical concerns.

Marshall Price

Posted: Sun Mar 23, 2008 11:37 am

Guest

Kumar wrote:

Quote:

On Mar 23, 6:38 pm, Marshall Price <d0213...@yahoo.com> wrote:
Kumar wrote:
Today, I looked at my daughter force-feeding her 2-year-old boy. Such
aided/forced or excessive feeding to kids can be common in most
mothers as a practice, misconception or just sentiment-- love &
affection. Can't it cause an acquired habit to overeat and expose more
insulin to target cells and mediating diabetes2?
I'd say she needs help -- either a book or a psychiatrist! What she's
doing is a well known, serious problem.

Yes, but how it can be relevant to getting diabetes2 afterwards?

There are at least three varieties of type 2 diabetes mellitus (DM2),
which is usually characterized by defective insulin secretion plus
resistance to the action of insulin. One variety is "maturity-onset
diabetes of the young" (MODY). (And there are six subtypes of MODY.)

Though I've got a book on diabetes and half a dozen with extended
discussions of it, it never particularly interested me, but I do know
it's both *complicated* and incompletely understood -- and I have no
idea why you're concerned about it, or how I can help.

However, common sense tells me (a) that force-feeding anybody (including
geese) is unhealthy and cruel, and (b) that you cannot draw upon fat
reserves in your body when they're "locked down" by insulin, which is an
unhealthy condition to be in, except briefly and immediately after a meal.

If you only put fat into your tissues and never take it out (all
anabolism and no catabolism: remember, "metabolism" means both!), and
you force your glucose transporters to react to insulin all the time,
and beyond their capacity, you're asking for trouble, such as fewer and
less responsive glucose transporters, which causes insulin resistance,
which means trouble.

But every book on childrearing contains advice on feeding infants, and
if your daughter really cared about her child, she'd pick one up and
read it. And if she doesn't, why don't you?

I'm reminded of the difference between returning opossums and raccoons
to the wild. Opossums are very stupid and live by instinct. As soon as
they're weaned, you can just let them go. But raccoons are very
intelligent and require a lot of education from their parents. If
they're brought up in captivity, they can never be released; there's
just too much they don't know, and nobody to teach them.

Well, humans need the most education of all. It's the way we've
evolved, learning from each other. Our instincts are gone, but our
minds are active, curious, and absorbent; and we've gotten used to it,
so we're stuck with it. We must either learn or be ignorant -- and if
we choose to be ignorant, we will surely suffer.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Marshall Price

Posted: Sun Mar 23, 2008 12:04 pm

Guest

Nico Kadel-Garcia wrote:

Quote:

Marshall Price wrote:
Kumar wrote:
Today, I looked at my daughter force-feeding her 2-year-old boy. Such
aided/forced or excessive feeding to kids can be common in most
mothers as a practice, misconception or just sentiment-- love &
affection. Can't it cause an acquired habit to overeat and expose more
insulin to target cells and mediating diabetes2?
I'd say she needs help -- either a book or a psychiatrist! What she's
doing is a well known, serious problem.

And it's irrelevant to Type 1 diabetes, and the causality of Type 2 and
obesity is often reversed: the Type 2 and high insulin levels trigger hunger,
and weight gain, exacerbating the diabetes. So force feeding infants is
something to worry about for plenty of other reasons, I'd consider the risk of
diabetes to be one of the least critical concerns.

Here's a good, brief page of advice for Kumar, assuming the baby's on
solid food.

http://www.aap.org/publiced/BR_NutritionABC.htm

It's from the American Academy of Pediatrics. I hope the text is legible:

----------

American Academy of Pediatrics

Nutrition

How do I know if my child is eating enough?

Children eat when they are hungry and usually stop when they are full.
Some parents worry because young children appear to eat very small
amounts of food, especially when compared to adult portions. A child who
is growing well is getting enough to eat.

To check your child's eating pattern, pay attention to his or her food
choices.

*
Make sure no one food group is completely left out. If this
happens for a few days, don't worry. But prolonged neglect of a food
group could keep your child from getting enough nutrients.
*
Encourage your child to be adventurous and eat a variety of foods
within the food groups, too. Even within a food group, different foods
provide different nutrients.

Child-size servings

For youngsters, adult-size servings can be overwhelming. Offering
child-size servings encourages food acceptance.

Here's an easy guide to child-size servings:

*
Serve one-fourth to one-third of the adult portion size, or one
measuring tablespoon for each year of the young child's age.
*
Give less than you think the child will eat. Let the child ask
for more if he or she is still hungry.

Snacks count

Snacks make up an important part of childhood nutrition. Children must
eat frequently. With their small stomachs, they cannot eat enough at
meals alone for their high energy needs. Three meals and two or three
healthful snacks a day help youngsters meet their daily nutrition needs.

To make the most of snacks, parents and caregivers should control the
type of snack and time it is served.

*
Type. Offer a variety of food-group snacks. Choose mostly snack
foods that supply enough nutrients to justify their energy, or calories.
*
Timing. Plan snacks. Schedule snacks around normal daily events,
and space them at least two hours before meals. Children should learn to
get and feel hungry, instead of feeling full all the time.

Foods to choose

*
From the Bread, Cereal, Rice and Pasta Group: a whole-grain
bread, crackers, cereal, grits, pasta, rice, bagel, tortilla, cornbread,
pita bread, muffin, English muffin, matzo crackers, rice cake, pancakes,
breadsticks, pretzels
*
From the Vegetable Group: asparagus, beets, bok choy, broccoli,
carrot, cauliflower, collard greens, corn, cucumber, green and red
peppers, green beans, jicama, kale, okra, peas, potato, pumpkin, snow
peas, squash, spinach, sweet potato, tomato, vegetable juices, zucchini
*
From the Fruit Group: apple, applesauce, apricot, banana,
berries, cantaloupe, fruit cocktail, figs, fruit juices, grapefruit,
kiwifruit, mango, nectarine, orange, papaya, peach, pear, plum,
pineapple, raisins, prunes, starfruit, strawberries, tangerine, watermelon
*
From the Milk, Yogurt and Cheese Group: skim, 1%, 2% and whole*
milk, yogurt, cheese, string cheese, cottage cheese, pudding, custard,
frozen yogurt, ice milk, calcium-fortified soybean milk
*
From the Meat, Poultry, Fish, Dry Beans, Eggs and Nuts** Group:
lean cuts of beef, veal, pork, ham and lamb; skinless chicken and
turkey; fish; shellfish; cooked beans (kidney beans, black-eyed peas,
pinto beans, lentils, black beans); refried beans (made without lard);
peanut butter; eggs; reduced-fat deli meats; tofu; nuts**; peanuts**

*Children under two years of age should only drink whole milk.

**Nuts, peanuts and seeds are not recommended for children under four
years of age because they are a choking hazard. Small pieces of hard,
uncooked fruits and vegetables also pose a choking hazard to children
under age four.

----------

--
Marshall Price of Miami
Known to Yahoo as d021317c

Page 1 of 2 Goto page 1, 2 Next All times are GMT - 5 Hours The time now is Sun Sep 07, 2008 7:46 am Science Forum Index