Insulin oscillations & Insulin resistance?

Hello,

Insulin's exposure to target cells in diabetic type2 can be continual
& increased either due to natural reasons by irregular eating habit,
modern lifestyle & stress OR as a result of medication programme.
Howver instabilties in natural Insulin oscillations can also be linked
to insulin resistance as per following quote:-

"Insulin oscillations

Insulin release from pancreas is pulsatile with a period of 3-6
minutes. [1]The insulin concentration in blood increases after meals
and gradually returns to basal levels during 1-2 hours. However, the
basal insulin level is not stable. It oscillates with a regular period
of 3-6 min. After a meal the amplitude of these oscillations increases
but the periodicity remains constant. [1] The oscillations are
believed to be important for insulin sensitivity by preventing
downregulation of insulin receptors in target cells. [1] Such down
regulation underlies insulin resistance, which is common in type 2
diabetes. It would therefore be advantageous to administer insulin to
diabetic patients in a manner mimicking the natural oscillations. [..
Disturbances of the insulin oscillations occur early in diabetes and
may contribute to insulin resistance.
* en.wikipedia.org/wiki/Insulin_release_oscillations "

Under such consideration, how this aspect alongwith increased
insulin's exposure resulting downregulation of insulin's receptors,
which can be common in type2 diabetics, address insulin resistance?

Best wishes.

I think you're asking what you do to keep IRS-1 and/or IRS-2 from
downregulating. There's an extensive literature for this. I don't
regularly follow it but this is what's in my notes. I suspect
intermittent fasting will also improve insulin sensitivity via IRS-1/2
but I haven't checked.

green tea increase insulin-stimulated glucose uptake and insulin binding
to adipocytes; EGCG mimics insulin by stimulating tyrosine
phosphorylation of the insulin receptor and IRS-1 and increases
phosphoinositide 3-kinase (PI3K), MAPK and p70, EGCG also inhibits
glucose production in the liver, possibly by repressing genes for
gluconeogenesis < * w w w .jbc.org/cgi/content/full/277/38/24933>

in obese rats, exercise training along with alpha lipoic acid improves
the skeletal muscle levels of IRS-1 (insulin receptor substrate-1),
glucose transport along with activity of p85 subunit of PI3K [PMID
15068957]

diabetes can be induced by knocking out both insulin receptor substrates
(IRS); low levels of IRS-1 in the liver prompt it to make more glucose
(upregulated gluconeogenic enzymes glucose-6 phosphatase and
phosphoenolpyruvate carboxykinase; also increased hepatic nuclear
factor-4 alpha; decreased glucokinase); low levels of IRS-2 made more
triglycerides (it upregulates SREBP-1c and fatty acid synthase and
increased fat accumulation in the liver); blocking both at the same time
lead to fatty liver disease (hepatic steatosis), glucose intolerance and
insulin resistance, defective Akt activation and Foxo1 phosphorylation
[PMID 15711641]

heard of "urine therapy" ---- 156,000 web pages on google.
Erach

On Mar 24, 3:33 pm, Kofi <k...@anon.un> wrote:
> I think you're asking what you do to keep IRS-1 and/or IRS-2 from
> downregulating.  There's an extensive literature for this.  I don't
> regularly follow it but this is what's in my notes.  I suspect
> intermittent fasting will also improve insulin sensitivity via IRS-1/2
> but I haven't checked.
>
> green tea increase insulin-stimulated glucose uptake and insulin binding
> to adipocytes; EGCG mimics insulin by stimulating tyrosine
> phosphorylation of the insulin receptor and IRS-1 and increases
> phosphoinositide 3-kinase (PI3K), MAPK and p70, EGCG also inhibits
> glucose production in the liver, possibly by repressing genes for
> gluconeogenesis < * w w w .jbc.org/cgi/content/full/277/38/24933>
>
> in obese rats, exercise training along with alpha lipoic acid improves
> the skeletal muscle levels of IRS-1 (insulin receptor substrate-1),
> glucose transport along with activity of p85 subunit of PI3K [PMID
> 15068957]
>
> diabetes can be induced by knocking out both insulin receptor substrates
> (IRS); low levels of IRS-1 in the liver prompt it to make more glucose
> (upregulated gluconeogenic enzymes glucose-6 phosphatase and
> phosphoenolpyruvate carboxykinase; also increased hepatic nuclear
> factor-4 alpha; decreased glucokinase); low levels of IRS-2 made more
> triglycerides (it upregulates SREBP-1c and fatty acid synthase and
> increased fat accumulation in the liver); blocking both at the same time
> lead to fatty liver disease (hepatic steatosis), glucose intolerance and
> insulin resistance, defective Akt activation and Foxo1 phosphorylation
> [PMID 15711641]

Should we not check if all conventional diabetic medication programme
to increase insulin senstiviy and availabilty can be directly or
indirenctly related to;

Insulin degradation
* edrv.endojournals.org/cgi/content/full/19/5/608#F1

Insulin Oscillations
* en.wikipedia.org/wiki/Insulin_release_oscillations

Downregulation
* en.wikipedia.org/wiki/Downregulation

Abnormalities in insulin's exposure, normal degradation & oscillation
can cause increased exposure to target cells resulting downregulation
so decreased senstivity.