kumar

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.

rep

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 ****ysis 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

kumar

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?

kumar

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.

kumar

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 "

kumar

"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 blood, 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 ****ogs.
http://arbl.cvmbs.colostate.edu/hbo...lin_struct.html "


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