Role Of The Kidney In Insulin Metabolism And Excretion
The role of the kidneys in insulin metabolism and excretion is reviewed. Removal of these organs from animals prolongs the half-life of injected labeled or unlabeled insulin. Similar findings, reversible by transplantation, are noted in patients with severe renal disease. After injection of insulin-I-131 into a peripheral vein, the concentration of radioactivity in the renal cortex of rats is nine times greater than any other tissue and 21 per cent of the administered dose is present in the kidneys at fifteen minutes. In contrast to other organs, an increase in the injected dose results in a greater proportion being localized to the kidneys. The concentration of insulin in renal venous blood is 30 to 40 per cent lower than the arterial level, and the quantity of insulin removed by the kidneys over twentyfour hours is 6 to 8 U. The renal clearance of insulin in man is approximately 200 ml. per minute. There is both direct and indirect evidence that insulin is filtered at the glomerulus and almost completely reabsorbed and degraded by cells lining the proximal convoluted tubules. This mechanism accounts for 50 to 60 per cent of the renal uptake of insulin, the remaining 40 to 50 per cent being removed from the postglomerular peritubular capillaries. The amount of insulin excreted in the urine is less than 2 per cent of the filtered load and the urinary clearance is 0.1-0.5 ml. per minute. This clearance is constant over a wide range of serum levels and is thus a useful reflection of the mean serum level over a period of time. These observations explain the fall in insulin requirements of diabetic patients who develop renal failure. Furthermore, the severe hypoglycemia which occasionally occurs in elderly subjects with uremia following the administration of oral sulfonylur Continue reading >>
Role Of The Kidney In Insulin Metabolism And Excretion
The role of the kidneys in insulin metabolism and excretion is reviewed. Removal of these organs from animals prolongs the half-life of injected labeled or unlabeled insulin. Similar findings, reversible by transplantation, are noted in patients with severe renal disease. After injection of insulin-I-131 into a peripheral vein, the concentration of radioactivity in the renal cortex of rats is nine times greater than any other tissue and 21 per cent of the administered dose is present in the kidneys at fifteen minutes. In contrast to other organs, an increase in the injected dose results in a greater proportion being localized to the kidneys. The concentration of insulin in renal venous blood is 30 to 40 per cent lower than the arterial level, and the quantity of insulin removed by the kidneys over twentyfour hours is 6 to 8 U. The renal clearance of insulin in man is approximately 200 ml. per minute. There is both direct and indirect evidence that insulin is filtered at the glomerulus and almost completely reabsorbed and degraded by cells lining the proximal convoluted tubules. This mechanism accounts for 50 to 60 per cent of the renal uptake of insulin, the remaining 40 to 50 per cent being removed from the postglomerular peritubular capillaries. The amount of insulin excreted in the urine is less than 2 per cent of the filtered load and the urinary clearance is 0.1-0.5 ml. per minute. This clearance is constant over a wide range of serum levels and is thus a useful reflection of the mean serum level over a period of time. These observations explain the fall in insulin requirements of diabetic patients who develop renal failure. Furthermore, the severe hypoglycemia which occasionally occurs in elderly subjects with uremia following the administration of oral sulfonylur Continue reading >>
The Renal Metabolism Of Insulin
Summary The kidney plays a pivotal role in the clearance and degradation of circulating insulin and is also an important site of insulin action. The kidney clears insulin via two distinct routes. The first route entails glomerular filtration and subsequent luminal reabsorption of insulin by proximal tubular cells by means of endocytosis. The second involves diffusion of insulin from peritubular capillaries and subsequent binding of insulin to the contraluminal membranes of tubular cells, especially those lining the distal half of the nephron. Insulin delivered to the latter sites stimulates several important processes, including reabsorption of sodium, phosphate, and glucose. In contrast, insulin delivered to proximal tubular cells is degraded to oligopeptides and amino-acids by one of two poorly delineated enzymatic pathways. One pathway probably involves the sequential action of insulin protease and either GIT or non-specific proteases; the other probably involves the sequential action of GIT and lysosomal proteases. The products of insulin degradation are reabsorbed into the peritubular capillaries, apparently via simple diffusion. Impairment of the renal clearance of insulin prolongs the half-life of circulating insulin by a number of mechanisms and often results in a decrease in the insulin requirement of diabetic patients. Much needs to be learned about these metabolic events at the subcellular level and how they are affected by disease states. Owing to the heterogeneity of cell types within the kidney and to their anatomical and functional polarity, investigation of these areas will be challenging indeed. Continue reading >>
Can Urine Tests Tell When Urine Was Produced?
The bladder can be drained with a catheter (a tube placed into the bladder). With the bladder empty, the urine that flows out of the tube is only a few minutes old. By collecting urine serially in small batches and timing the collections, the urine can indeed be given a timestamp of sorts. We used to measure kidney function this way by giving a shot of medicine that is released by the kidney in a predictable way. By measuring and timing, we could tell how fast the kidney was filtering the blood, which is an important thing to know in many conditions. Check out the inulin (mind the spelling, it's not insulin) excretion test for more info. Continue reading >>
What Is The Main Cause Of Diabetes?
There is no common diabetes cause that fits every type of diabetes. The causes of diabetes can depend on a variety of factors like your genetic makeup, family history, ethnicity, health, and also on environmental factors. Some of the known causes of diabetes treatment are: Type 1 diabetes This type of diabetes is caused by the immune system destroying the beta cells in the pancreas that make insulin. This leaves the body without enough insulin to function normally. Some other causes of type 1 disease also include viral or bacterial infection, release of chemical toxins within food, eating more food than usual, etc. Type 2 diabetes This type of diabetes generally occurs when the pancreas does not produce any insulin, or produce very little insulin or the body stops responding to insulin, a condition called insulin resistance. Some other causes of type 2 diabetes are obesity, living a sedentary life, increasing age, bad diet, pregnancy and illness etc. Gestational diabetes This type of diabetes generally affects females during pregnancy, the cause of which has still not been known accurately. However the number of risk factors that can lead to this disease are being overweight, family history of gestational diabetes, suffering from polycystic ovary syndrome or even having a large baby weighing over 9lbs. Some other diabetes causes are: Cushing’s syndrome- This syndrome increases the production of the cortisol hormone, which results in increased blood glucose levels. Glucagonoma- Patients with glucagonoma may experience diabetes because of a lack of equilibrium between levels of insulin production and glucagon production Continue reading >>
The Renal Handling Of Insulin*
Abstract The renal handling of insulin was studied by insulin immunoassay in arterial blood, renal venous blood, and urine of fasting patients with normal renal function and in peripheral venous blood and urine of normal subjects and patients with renal disease before and after an oral glucose load. A renal arteriovenous insulin concentration difference of approximately 29% was found and suggests that in normal subjects renal insulin clearance is significantly in excess of glomerular filtration rate. The insulin excreted in the urine of normal individuals at no time exceeded 1.5% of the load filtered at the glomerulus. This contrasts with the finding of a urinary insulin clearance approaching glomerular filtration rate in patients with severely impaired renal tubular function. It is suggested that insulin is normally filtered at the glomerulus and then almost completely reabsorbed or destroyed in the proximal tubule. If reabsorption occurs, as seems more likely, reabsorbed insulin does not return to the renal vein and is presumably utilized in renal metabolism together with insulin taken up directly from the blood. Caution is advised in the use of urinary insulin concentration or excretion as an index of serum insulin level or insulin secretion because a very small and variable proportion of filtered insulin appears in the urine in normal subjects, and major changes in urinary insulin excretion may arise as a result of minor tubular defects. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. These references are in PubMed. This may not be the complete list of refe Continue reading >>
What Causes Diabetes, And How Is It Treated?
It depends on which type of diabetes you have. This is a long answer, but you're asking a very complex question, so please bear with me. The basic power source for our body is glucose, which is produced from almost anything we eat (carbohydrates, proteins, sugars, and fats). It is usually tightly regulated by the body, so that when you have excess glucose in the blood, it is taken out of the blood and stored–but when the blood glucose drops, it is then released from storage to be used for energy. The key hormone, insulin, which regulates the level of glucose in the body is released by the Beta cells of the Islets of Langerhans in the pancreas when blood sugar goes up–insulin induces storage cells to remove and store glucose from the blood. In a complex interaction, the hormone glucagon, produced by other cells in the pancreas when the blood glucose level is too low, which then induces release of that stored glucose. (This once again goes to show how complex living systems are, and simple explanations are laughable and should be dismissed.) It’s a fascinating system of the body, and it’s remarkable that it works so well in 99% of people. Type 1 diabetes is an autoimmune disease where the body’s own antibodies attack the Islets of Langerhans, causing the production of insulin to drop or even to be halted. As of today, there are no cures, and the only way to treat someone is to regularly inject human insulin, which is produced by bioengineered E. coli. Ironically, the human insulin gene has been inserted in GM safflower, to be used as another method of mass-producing human insulin. Before the wide availability of insulin in the 1920’s (usually pig insulin whose structure is similar to human insulin, but still caused a lot of allergic reactions), children simply Continue reading >>
Diabetes Drugs: Insulin
Editor’s Note: This is the first post in our miniseries about diabetes drugs. Tune in on August 14 for the next installment. Insulin was the first medicine developed for the treatment of diabetes, and it remains the most effective therapy for treating hyperglycemia (high blood glucose). The name insulin comes from the Latin insula which means island; it is so named because the beta cells, which produce insulin, are in a part of the pancreas called the islets of Langerhans. Insulin is a protein consisting of 51 amino acids. It is normally released into the blood in response to changes in blood glucose levels, but several hormones, nutrients, and drugs can also stimulate its release. Insulin therapy is required for all people with Type 1 diabetes and for many people with Type 2 diabetes. While people with Type 1 diabetes lack insulin secretion due to the autoimmune destruction of the pancreatic beta cells (a process in which the immune system recognizes the beta cells as foreign to the body, and so attacks them), people with Type 2 diabetes have a mixture of insensitivity to insulin (called insulin resistance) and a decrease in insulin secretion (which may be due either to poorly functioning beta cells or to a decrease in the amount of beta cells). Insulin reduces blood glucose levels by interacting with a protein on the surface of cells called the insulin receptor. There are two known types of insulin receptor that both serve the same purpose. The interaction between insulin and the insulin receptor triggers a complex series of reactions that are to date not fully understood, but that serve to increase the creation of protein, glycogen (a storage form of glucose), and most importantly, glucose transport proteins (proteins that bring glucose from the blood into the cell Continue reading >>
Insulin Synthesis And Secretion
Insulin is a small protein, with a molecular weight of about 6000 Daltons. It is composed of two chains held together by disulfide bonds. The figure to the right shows a molecular model of bovine insulin, with the A chain colored blue and the larger B chain green. You can get a better appreciation for the structure of insulin by manipulating such a model yourself. The amino acid sequence is highly conserved among vertebrates, and insulin from one mammal almost certainly is biologically active in another. Even today, many diabetic patients are treated with insulin extracted from pig pancreas. Biosynthesis of Insulin Insulin is synthesized in significant quantities only in beta cells in the pancreas. The insulin mRNA is translated as a single chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. Proinsulin consists of three domains: an amino-terminal B chain, a carboxy-terminal A chain and a connecting peptide in the middle known as the C peptide. Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm. When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C peptide is also secreted into blood, but has no known biological activity. Control of Insulin Secretion Insulin is secreted in primarily in response to elevated blood concentrations of glucose. This makes sense because insulin is "in charge" of facilitating glucose entry into cells. Some neural stimuli (e.g. sight and taste of food) Continue reading >>
- Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)
- Insulin, glucagon and somatostatin stores in the pancreas of subjects with type-2 diabetes and their lean and obese non-diabetic controls
- Only 2 Ingredients and You Can Say Goodbye to Diabetes Forever! No More Medications and Insulin!!!
How Is Insulin Excreted From The Pancreas? - Quora
How is insulin excreted from the pancreas? aJduSYDV JbYbAEfyZgSis RnueDUqeZuecTHakUDoAAEuZsJcPqsRhkGiGYtGzoD What's a meaningful resolution I can make (and actually keep) for 2020? You've likely made a resolution in the past that turned out... well, let's just say it didn't turn out so well. Not this year!... Updated Aug 30, 2019 Author has 1.1k answers and 1.3m answer views (1) Endocrine function -Under the endocrine function it releases substances directly into the stream.The endocrine portion of the pancreas form many small cluster of cells and is called Islets of Langerhans. A human has roughly one million islets. The pancreatic islets has three major type of cells. (A) Alpha cells- It secrete the hormone called Glucagon. When we keep fast or if we do not take food, our body becomes glucose deficient. In such a situation the pancreas secrete the hormone called Glucagon. Which in turn signals our Liver to release stored glucose so a... (1) Endocrine function -Under the endocrine function it releases substances directly into the stream.The endocrine portion of the pancreas form many small cluster of cells and is called Islets of Langerhans. A human has roughly one million islets. The pancreatic islets has three major type of cells. (A) Alpha cells- It secrete the hormone called Glucagon. When we keep fast or if we do not take food, our body becomes glucose deficient. In such a situation the pancreas secrete the hormone called Glucagon. Which in turn signals our Liver to release stored glucose so as to maintain the required glucose level in the body. That means the glucagon acts to raise blood sugar. (B) Beta cells- it produces a hormone called Insulin. When we eat food. The Glucose level in our body increases. The moment the glucose level increases the pancreas(Beta Continue reading >>
Insulin
This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body.[5] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.[6] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[6] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[7] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.[8] Their neighboring alpha cells, by taking their cues from the beta cells,[8] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[6][8] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[6][8] The secretion of insulin and glucagon into the Continue reading >>
Fate Of Insulin In The Normal And Diabetic Organism
FATE OF INSULIN IN THE NORMAL AND DIABETIC ORGANISM JAMA. 1949;140(17):1344. doi:10.1001/jama.1949.02900520030012 Little has been known of the ultimate fate of insulin in the human organism. Obviously, insulin is constantly being eliminated; otherwise cumulative effects manifested by periods of severe hypoglycemia would be observed even in normal subjects. As is well known, however, the blood sugar level is maintained remarkably constant in normal persons. At least two different methods of disposing of insulin appear possible: one by excretion in the urine or possibly feces (via bile) and the other by destruction in the body. The first route, that of excretion, would not appear to be of major importance. The elimination of protein molecules as large as that of insulin (molecular weight 35,000) seldom takes place to any significant extent in the normal kidney and probably not in the bile or feces. Support for this statement is to be found in a recent study1 in which it was reported that the urine Continue reading >>
Insulin Stimulates Uric Acid Reabsorption Via Regulating Urate Transporter 1 And Atp-binding Cassette Subfamily G Member 2
Insulin stimulates uric acid reabsorption via regulating urate transporter 1 and ATP-binding cassette subfamily G member 2 Accumulating data indicate that renal uric acid (UA) handling is altered in diabetes and by hypoglycemic agents. In addition, hyperinsulinemia is associated with hyperuricemia and hypouricosuria. However, the underlying mechanisms remain unclear. In this study, we aimed to investigate how diabetes and hypoglycemic agents alter the levels of renal urate transporters. In insulin-depleted diabetic rats with streptozotocin treatment, both UA excretion and fractional excretion of UA were increased, suggesting that tubular handling of UA is altered in this model. In the membrane fraction of the kidney, the expression of urate transporter 1 (URAT1) was significantly decreased, whereas that of ATP-binding cassette subfamily G member 2 (ABCG2) was increased, consistent with the increased renal UA clearance. Administration of insulin to the diabetic rats decreased UA excretion and alleviated UA transporter-level changes, while sodium glucose cotransporter 2 inhibitor (SGLT2i) ipragliflozin did not change renal UA handling in this model. To confirm the contribution of insulin in the regulation of urate transporters, normal rats received insulin and separately, ipragliflozin. Insulin significantly increased URAT1 and decreased ABCG2 levels, resulting in increased UA reabsorption. In contrast, the SGLT2i did not alter URAT1 or ABCG2 levels, although blood glucose levels were similarly reduced. Furthermore, we found that insulin significantly increased endogenous URAT1 levels in the membrane fraction of NRK-52E cells, the kidney epithelial cell line, demonstrating the direct effects of insulin on renal UA transport mechanisms. These results suggest a previously Continue reading >>
Does Your Body Process 200g Of Sugar The Same Way If You Ingest That Quantity In 5 Minutes Or Throughout The Whole Day?
No. If you consume small amount throughout the day, sugar will either be used as instant energy or it will be taken up by liver to synthesize glycogen. If you consume 200 grams at once,and if all of that is absorbed, there will be release of large amount of insulin to maintain blood sugar level within normal range. 200g is too much for liver to take up. Given that insulin promotes formation of adipose tissue, rest of the sugar will be stored in body as fat. If blood sugar level exceeds renal threshold for glucose- 200 mg/dl, then glucose will be excreted in urine. some additional information on role of insulin and glucagon in regulation of blood sugar level: blood sugar level in body is maintained within narrow range. Any rise in blood sugar level causes release of insulin within few minutes which will mobilize this sugar in tissues and blood sugar level is again brought down to normal resting level. As the blood sugar level decreases in blood,insulin secretion also decreases simultaneously. See the following diagram for better understanding. A number of other hormones influence blood sugar level. All hormones increase it except insulin.(and insulin like growth factor). Continue reading >>
The Excretion Of Insulin In Urine
Summary The concentration of biologically active insulin was measured by the isolated fat cell method in serum and urine from healthy subjects and compared with the concentration of immunoreactive insulin. In both urine and serum the values obtained by the two methods correlated closely. In addition, there was a close correlation between the concentration of biologically active and immunoreactive insulin in urine from maturity onset diabetics. Therefore, conclusions on the excretion in the urine and the urinary clearance of insulin, which are based on measurements of immunoreactive insulin, are also valid for biologically active insulin. Continue reading >>
