Clearance/loss of Insulin & Diabetes?

[Kumar]

Hello,

It is well understood that a diabetic patient with kidney failure 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 secretion/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)?

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 GFR due to increased pressure.

3. Whether diabetic patients are in a better position than non-diabetic/ hypertensive people in respect of getting hypoglycemic episodes on kindney failure? How non-diabetic patients with kidney failure can handle possible hypoglycemic episodes due to decreased urinary excretion of insulin?

4. Familial history can cause predisposed defects in our intake & excretion, to which modern lifestyle can add the fuel. So, can real cause of getting diabetes2/IR be the defects in our intake & excretion instead as otherwise thought?

Best wishes.

Ref.;

Insulin uptake and degradation is a complex and not yet completely understood process involving not only insulin sensitive tissues. The most important degradative system is insulin degrading enzyme which is a highly conserved metalloendopeptidase requiring Zn++ for its proteolytic action, although protein disulfide isomerase and cathepsin D are also involved in insulin metabolism. The liver and the kidney are the principal sites for insulin clearance. In obese subjects with hyperinsulinemia and high levels of free fatty acids, insulin hepatic clearance is impaired, while the glomerular filtration rate, renal plasma flow and albumin excretion are increased, suggesting a state of renal vasodilatation leading to an abnormally transmitted arterial pressure to the glomerular capillaries through a dilated afferent arteriole. Insulin can be cleared also by muscle, adipocytes, gastrointestinal cells, fibroblasts, monocytes and lymphocytes which contain insulin receptors and internalization and regulation mechanism for insulin metabolism. http://www.jacn.org/cgi/content/abstract/22/6/487

 

[Kumar]

Type 2 diabetic patients at baseline showed glomerular hyperfiltration compared with healthy control subjects. Rosiglitazone reduced elevated GFR and filtration fraction toward control primarily in patients with microalbuminuria (GFR: 133.4 +/- 9.8 vs. 119.6 +/- 8.7 ml/min; filtration fraction: 23.2 +/- 1.7 vs. 20.5 +/- 1.6% before and after rosiglitazone, respectively; control subjects: GFR 111.7 +/- 8.6 ml/min, filtration fraction 20.4 +/- 1.5%). Rosiglitazone improved intrarenal NO bioavailability in type 2 diabetes toward control as shown by infusion of L-NMMA. Rosiglitazone reduced albumin excretion in type 2 diabetes with microalbuminuria from 116.5 +/- 31 to 40.4 +/- 12 mg/day. Rosiglitazone ameliorated glomerular hyperfiltration in early type 2 diabetes, improved NO bioavailability, and lessened renal end-organ damage in type 2 diabetes with microalbuminuria.
http://www.ncbi.nlm.nih.gov/entrez/...d&dopt=Abstract&list_uids=15983223&query_hl=3

This is also related to effect on GFR by one insulin senstiser. Hyperfiltration may be related to hyperglycemia.

 

[Kumar]

Inspite of such an important aspect, I feel surprised that no one could tell me anything.

 

[Kumar]

????

It looks "Renal insulin clearance" & "Renal regulation of insulin" may be possible in view of following & some other links:-

"Insulin excretion was greater in diabetic than normal children in both sexes at all puberty stages. Insulin clearance was also greater in diabetic than normal subjects (1.05 +/- 0.1 ml min-1 1.73 m-2 vs 0.48 +/- 0.05 ml min-1 1.73 m-2, p < 0.001). Insulin excretion as a percentage of the filtered load was also greater in diabetic than normal subjects (1.9 +/- 0.27% vs 0.85 +/- 0.09%, p < 0.01)."
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

"Diabetic Nephropathy
Complications
Possible complications include:
hypoglycemia (from decreased excretion of insulin)"

http://www.nlm.nih.gov/medlineplus/ency/article/000494.htm

However, it is also considered that, bigger molecules of protien are not filtered by kidneys. All these aspects look bit contradictory. But if renal clearance & regulation of insulin is valid, it can be of great importance. Probably, insulin is deformed due to altered environment internally & in kidneys so urine may just show insulin as protiens.

 

[Kumar]

Pls also look at following links:-

Filtration
In the nephron, approximately 20 percent of the blood gets filtered under pressure through the walls of the glomerular capillaries and Bowman's capsule. The filtrate is composed of water, ions (e.g. sodium, potassium, chloride), glucose and small proteins (less than 30,000 daltons -- a dalton is a unit of molecular weight).
http://science.howstuffworks.com/kidney4.htm
In humans, insulin has a molecular weight of 5734.
http://en.wikipedia.org/wiki/Insulin

Structure of Insulin
Insulin is a rather small protein, with a molecular weight of about 6000 Daltons.
http://arbl.cvmbs.colostate.edu/hboo...s/insulin.html

Humalog has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.

http://www.rxlist.com/cgi/generic/insulinlispro.htm

All above links indicate that size of insulin molecule is smaller than kidney's capacity. Why then, there can't be renal clearance & regulation of insulin?