Insulin: Insulin resistance or Renal Loss?
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kuma #1 / 10
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 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.
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Sat, 31 May 2008 12:01:29 GMT |
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REP #2 / 10
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 Insulin: Insulin resistance or Renal Loss?
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> 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
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Sat, 31 May 2008 18:04:27 GMT |
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kuma #3 / 10
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 Insulin: Insulin resistance or Renal Loss?
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> > 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?
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Sat, 31 May 2008 18:49:06 GMT |
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Kuma #4 / 10
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 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 "
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Thu, 12 Jun 2008 00:23:04 GMT |
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Andrew B. Chung, MD/Ph #5 / 10
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 Insulin: Insulin resistance or Renal Loss?
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> 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
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Thu, 12 Jun 2008 00:30:18 GMT |
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kuma #6 / 10
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 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
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Thu, 12 Jun 2008 02:30:14 GMT |
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Andrew B. Chung, MD/Ph #7 / 10
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 Insulin: Insulin resistance or Renal Loss?
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> > > 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
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Thu, 12 Jun 2008 03:14:12 GMT |
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kuma #8 / 10
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 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/
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Thu, 12 Jun 2008 12:13:32 GMT |
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kuma #9 / 10
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 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/
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Fri, 13 Jun 2008 01:44:19 GMT |
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kuma #10 / 10
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 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?
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Sat, 14 Jun 2008 11:02:44 GMT |
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