Insulin: Insulin resistance or Renal Loss? 
Author Message
 Insulin: Insulin resistance or Renal Loss?

Hello,

I tried to clear this point in another topic but it is not yet clear to
me.

It is well understood that a diabetic patient on getting diaetic
nephropathy(DN) can
experiance hypoglycemia or lower requirement of insulin due to
decreased excretion of insulin in urine. But I want to know that:-

1. Can there be increased excretion/loss of insulin in urine due to
polyuria/fluid overload due to polydypsia or due to any other
disorder(may be due to high pressure in renal capalliries) resulting
into hyperglycemia, diabetes2 or Insulin Resistance(IR)? Renal loss may
be in intact insulin or in some degraded/destroyed form in kidneys.

2. Instead as thought about IR, can persistence of this urinary loss of

insulin be a real picture of Insulin resistance? Obesity(a cause,
thought for getting IR) can increase renal filteration due to increased
pressure.

3. Is it not bit contradictory: protiens being bigger molecules are
said to be, not normally filtered in normal health but are lost in case
of DN/kidney failure WHEREAS insulin's decreased excretion on getting
DN? Insulin molecular weight is below 6000 D whereas kidney can filter
upto 30000 D.

Best wishes.



Sat, 31 May 2008 12:01:29 GMT
 Insulin: Insulin resistance or Renal Loss?

Quote:

> Hello,

> I tried to clear this point in another topic but it is not yet clear to
> me.

> It is well understood that a diabetic patient on getting diaetic
> nephropathy(DN) can
> experiance hypoglycemia or lower requirement of insulin due to
> decreased excretion of insulin in urine. But I want to know that:-

> 1. Can there be increased excretion/loss of insulin in urine due to
> polyuria/fluid overload due to polydypsia or due to any other
> disorder(may be due to high pressure in renal capalliries) resulting
> into hyperglycemia, diabetes2 or Insulin Resistance(IR)? Renal loss may
> be in intact insulin or in some degraded/destroyed form in kidneys.

Metabolism. 2001 Aug;50(8):863-7.
?
The renal metabolism of insulin: urinary insulin excretion in patients
with mutant insulin syndrome (insulin Wakayama).

Hanabusa T, Oki C, Nakano Y, Okai K, Nishi M, Sasaki H, Sanke T, Nanjo K.

First Department of Medicine, Wakayama University of Medical Science,
Wakayama, Japan.

Many studies have shown that the kidney plays an important role in the
metabolism of many proteins and small peptides. To understand insulin
handling in the kidney, we examined urinary insulin excretion under
several conditions in patients with mutant insulin syndrome (MIS;
insulin Wakayama). Urinary excretion of insulin was studied using
high-performance liquid chromatography analysis in patients with MIS. In
these patients, most of the insulin extracted from a 24-hour urine
collection and from urine collected after stimulation of insulin
secretion by glucose or glucagon was normal insulin, whereas 90% of
serum insulin is structurally abnormal (Leu-A3 insulin). On the other
hand, arginine, which is known as an inhibitor of renal tubular
reabsorption, increased urinary excretion of Leu-A3 insulin. The ratio
of Leu-A3 and normal insulin in urine after arginine was similar to that
in serum. A large amount of Leu-A3 insulin is excreted in urine when
reabsorption of insulin at renal tubules is inhibited by arginine. These
data indicate that normal and Leu-A3 insulin are filtered through the
glomerulus with relatively little restriction. Using the fact that basal
urine has a high concentration of normal insulin and an extremely low
concentration of Leu-A3 insulin, which has less receptor-binding
affinity, we speculated some possibilities. One possibility is that both
forms of insulin are reabsorbed by the tubular cells, but with different
efficiencies. Leu-A3 insulin absorption in more complete, and this
suggests differences in the uptake pathways that may account for the
differences in response to arginine infusions. Another possibility is
that only normal insulin is secreted from tubules into urine which is
mediated by receptors. Our results provide new insight into renal
metabolism of insulin and showed that MIS is a useful model for studying
it.

--
"Did Father shoot him? I will eat Grandfather for dinner."
- Helen Keller, on learning of the death of her grandfather



Sat, 31 May 2008 18:04:27 GMT
 Insulin: Insulin resistance or Renal Loss?

Quote:



> > Hello,

> > I tried to clear this point in another topic but it is not yet clear to
> > me.

> > It is well understood that a diabetic patient on getting diaetic
> > nephropathy(DN) can
> > experiance hypoglycemia or lower requirement of insulin due to
> > decreased excretion of insulin in urine. But I want to know that:-

> > 1. Can there be increased excretion/loss of insulin in urine due to
> > polyuria/fluid overload due to polydypsia or due to any other
> > disorder(may be due to high pressure in renal capalliries) resulting
> > into hyperglycemia, diabetes2 or Insulin Resistance(IR)? Renal loss may
> > be in intact insulin or in some degraded/destroyed form in kidneys.

> Metabolism. 2001 Aug;50(8):863-7.

> The renal metabolism of insulin: urinary insulin excretion in patients
> with mutant insulin syndrome (insulin Wakayama).

> Hanabusa T, Oki C, Nakano Y, Okai K, Nishi M, Sasaki H, Sanke T, Nanjo K.

> First Department of Medicine, Wakayama University of Medical Science,
> Wakayama, Japan.

> Many studies have shown that the kidney plays an important role in the
> metabolism of many proteins and small peptides. To understand insulin
> handling in the kidney, we examined urinary insulin excretion under
> several conditions in patients with mutant insulin syndrome (MIS;
> insulin Wakayama). Urinary excretion of insulin was studied using
> high-performance liquid chromatography analysis in patients with MIS. In
> these patients, most of the insulin extracted from a 24-hour urine
> collection and from urine collected after stimulation of insulin
> secretion by glucose or glucagon was normal insulin, whereas 90% of
> serum insulin is structurally abnormal (Leu-A3 insulin). On the other
> hand, arginine, which is known as an inhibitor of renal tubular
> reabsorption, increased urinary excretion of Leu-A3 insulin. The ratio
> of Leu-A3 and normal insulin in urine after arginine was similar to that
> in serum. A large amount of Leu-A3 insulin is excreted in urine when
> reabsorption of insulin at renal tubules is inhibited by arginine. These
> data indicate that normal and Leu-A3 insulin are filtered through the
> glomerulus with relatively little restriction. Using the fact that basal
> urine has a high concentration of normal insulin and an extremely low
> concentration of Leu-A3 insulin, which has less receptor-binding
> affinity, we speculated some possibilities. One possibility is that both
> forms of insulin are reabsorbed by the tubular cells, but with different
> efficiencies. Leu-A3 insulin absorption in more complete, and this
> suggests differences in the uptake pathways that may account for the
> differences in response to arginine infusions. Another possibility is
> that only normal insulin is secreted from tubules into urine which is
> mediated by receptors. Our results provide new insight into renal
> metabolism of insulin and showed that MIS is a useful model for studying
> it.

> --
> "Did Father shoot him? I will eat Grandfather for dinner."
> - Helen Keller, on learning of the death of her grandfather

Thanks. What can you make out from above study about renal
metabolism/renal loss of insulin in normal person and in diabetic type2
patients? Can there be increased or decreased loss, excretion or damage
of intact insulin via kidneys is possible or not? If possible, then
what about IR(insulin resistance) condition?


Sat, 31 May 2008 18:49:06 GMT
 Insulin: Insulin resistance or Renal Loss?
Btw, can insulin molecules exist in body in cluster/liquid crystal or
macromoecular form so not filtered via kidneys?

What does it mean:-

"Crystal:
a regular repeat of molecules, usually with some sort of internal
rotational symmetry. Protein crystals are usually about 40-60% solvent
by weight and are thus fragile and sensitive to drying out.
http://adelie.biochem.queensu.ca/~rlc/work/teaching/definitions.shtml "



Thu, 12 Jun 2008 00:23:04 GMT
 Insulin: Insulin resistance or Renal Loss?

Quote:

> Btw, can insulin molecules exist in body in cluster/liquid crystal or
> macromoecular form so not filtered via kidneys?

Insulin is a cross-linked polypeptide.  Only abnormal kidneys won't
filter out a molecule of this size.

Would be more than happy to "glow" and chat about this and other things
like cardiology, diabetes and nutrition that interest those following
this thread here during the next on-line chat (12/29/05) from 6 to 7 pm
EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Many Christmas blessings,

Andrew
http://tinyurl.com/b6xwk



Thu, 12 Jun 2008 00:30:18 GMT
 Insulin: Insulin resistance or Renal Loss?


Quote:

> > Btw, can insulin molecules exist in body in cluster/liquid crystal or
> > macromoecular form so not filtered via kidneys?

> Insulin is a cross-linked polypeptide.  Only abnormal kidneys won't
> filter out a molecule of this size.

Do you mean that normal kidneys will filter out molecules of insulin?
Do we normally loose insulin in urine?
Quote:
> Would be more than happy to "glow" and chat about this and other things
> like cardiology, diabetes and nutrition that interest those following
> this thread here during the next on-line chat (12/29/05) from 6 to 7 pm
> EST:

> http://tinyurl.com/cpayh

> For those who are put off by the signature, my advance apologies for
> how the LORD has reshaped me:

> http://tinyurl.com/bgfqt

> Many Christmas blessings,

> Andrew
> http://tinyurl.com/b6xwk



Thu, 12 Jun 2008 02:30:14 GMT
 Insulin: Insulin resistance or Renal Loss?

Quote:



> > > Btw, can insulin molecules exist in body in cluster/liquid crystal or
> > > macromoecular form so not filtered via kidneys?

> > Insulin is a cross-linked polypeptide.  Only abnormal kidneys won't
> > filter out a molecule of this size.

> Do you mean that normal kidneys will filter out molecules of insulin?

Yes.

Quote:
> Do we normally loose insulin in urine?

No.

Would be more than happy to "glow" and chat about this and other things
like cardiology, diabetes and nutrition that interest those following
this thread here during the next on-line chat (12/29/05) from 6 to 7 pm
EST:

http://tinyurl.com/cpayh

For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:

http://tinyurl.com/bgfqt

Many Christmas blessings,

Andrew
http://tinyurl.com/b6xwk



Thu, 12 Jun 2008 03:14:12 GMT
 Insulin: Insulin resistance or Renal Loss?
Is it not bit contradictary that kidneys will filterout insulin but not
lost in urine? Whether filtered insulin is reabsorbed in its origional
form under normal health?

Can/does endogenous insulin exist in {*filter*}/ECF as macromolecule/cluster
or crystal restrictiong its filterations as per need?

Quote:



> > > > Btw, can insulin molecules exist in body in cluster/liquid crystal or
> > > > macromoecular form so not filtered via kidneys?

> > > Insulin is a cross-linked polypeptide.  Only abnormal kidneys won't
> > > filter out a molecule of this size.

> > Do you mean that normal kidneys will filter out molecules of insulin?

> Yes.

> > Do we normally loose insulin in urine?

> No.

> Would be more than happy to "glow" and chat about this and other things
> like cardiology, diabetes and nutrition that interest those following
> this thread here during the next on-line chat (12/29/05) from 6 to 7 pm
> EST:

> http://www.***.com/

> For those who are put off by the signature, my advance apologies for
> how the LORD has reshaped me:

> http://www.***.com/

> Many Christmas blessings,

> Andrew
> http://www.***.com/



Thu, 12 Jun 2008 12:13:32 GMT
 Insulin: Insulin resistance or Renal Loss?
"Insulin, growth hormone, prolactin and other water-soluble polypeptide
hormones consist of long chains of amino acids, from several to 200
amino acids long. They are stored in endocrine cells until needed to
regulate such processes as metabolism, lactation, growth and
reproduction.
Water Vs. Fat Soluble
Most water-soluble hormones, like the amino acid derivatives and
peptides, can travel freely in the {*filter*} because they "like" water.
However, they are repelled by lipid or fatty structures such as the
membranes that surround the cell and nucleus. Because of this, these
hormones generally bind to receptor sites on the outside of the cell
and signal from there.
Fat-soluble hormones, like the sex hormone steroids estrogens and
androgens, are fat soluble and water repellent. That is, they "like"
lipid or fatty structures such as those surrounding cells but are
generally repelled by watery areas."
http://www.***.com/


Quote:



> > > > Btw, can insulin molecules exist in body in cluster/liquid crystal or
> > > > macromoecular form so not filtered via kidneys?

> > > Insulin is a cross-linked polypeptide.  Only abnormal kidneys won't
> > > filter out a molecule of this size.

> > Do you mean that normal kidneys will filter out molecules of insulin?

> Yes.

> > Do we normally loose insulin in urine?

> No.

> Would be more than happy to "glow" and chat about this and other things
> like cardiology, diabetes and nutrition that interest those following
> this thread here during the next on-line chat (12/29/05) from 6 to 7 pm
> EST:

> http://www.***.com/

> For those who are put off by the signature, my advance apologies for
> how the LORD has reshaped me:

> http://www.***.com/

> Many Christmas blessings,

> Andrew
> http://www.***.com/



Fri, 13 Jun 2008 01:44:19 GMT
 Insulin: Insulin resistance or Renal Loss?
"Insulin molecules have a tendency to form dimers in solution due to
hydrogen-bonding between the C-termini of B chains. Additionally, in
the presence of zinc ions, insulin dimers associate into hexamers.

These interactions have important clinical ramifications. Monomers and
dimers readily diffuse into {*filter*}, whereas hexamers diffuse very
poorly. Hence, absorption of insulin preparations containing a high
proportion of hexamers is delayed and slow. This problem, among others,

has stimulated development of a number of recombinant insulin analogs.
http://www.***.com/ ;

The above link tells that insulin have tendancy o
crystallize---whenther in case of endogenous insulin in {*filter*}/ECF  or
not is to be understood?



Sat, 14 Jun 2008 11:02:44 GMT
 
 [ 10 post ] 

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