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Renal Clearance Of Insulin

Renal Clearance Of Inulin Measurement Of Gfr

Renal Clearance Of Inulin Measurement Of Gfr

If a substance is neither reabsorbed nor secreted by the tubules, the amount excreted in the urine per minute will be equal to the amount that is filtered out of the glomeruli per minute. There does not seem to be a single substance produced by the body, however, that is not reabsorbed or secreted to some degree. Plants such as artichokes, dahlias, onions, and garlic, fortunately, do produce such a compound. This compound, a polymer of the monosaccharide fructose, is inulin. Once injected into the blood, inulin is filtered by the glomeruli, and the amount of in-ulin excreted per minute is exactly equal to the amount that was filtered per minute (fig. 17.22). If the concentration of inulin in urine is measured and the rate of urine formation is determined, the rate of inulin excretion can easily be calculated: where Quantity excreted per minute = V x U (mg/min) | f ml N \ fmg' V min, I V ml. rate of urine formation inulin concentration in urine The rate at which a substance is filtered by the glomeruli (in milligrams per minute) can be calculated by multiplying the milliliters of plasma filtered per minute (the glomerular Ureter urine containing all inulin that was filtered To peritubular capillaries Renal vein inulin concentration lower than in renal artery Ureter urine containing all inulin that was filtered ■ Figure 17.22 The renal clearance of inulin. (a) Inulin is present in the blood entering the glomeruli, and (b) some of this blood, together with its dissolved inulin, is filtered. All of this filtered inulin enters the urine, whereas most of the filtered water is returned to the vascular system (is reabsorbed). (c) The blood leaving the kidneys in the renal vein, therefore, contains less inulin than the blood that entered the kidneys in the renal artery. Since Continue reading >>

Effect Of Hyperinsulinemia On Renal Function In A General Japanese Population: The Hisayama Study - Sciencedirect

Effect Of Hyperinsulinemia On Renal Function In A General Japanese Population: The Hisayama Study - Sciencedirect

Volume 55, Issue 6 , June 1999, Pages 2450-2456 Clinical Nephrology Epidemiology Clinical Trials Effect of hyperinsulinemia on renal function in a general Japanese population: The Hisayama study Author links open overlay panel MichiakiKubo Effect of hyperinsulinemia on renal function in a general Japanese population: The Hisayama study. Insulin resistance and hyperinsulinemia induce glomerular hypertension and hyperfiltration, which may result in glomerulosclerosis. However, the relationship between hyperinsulinemia and renal function is uncertain. To elucidate whether hyperinsulinemia plays a significant part in the initiation and development of renal dysfunction, we examined in 1988 the relationship between serum insulin and renal function on data from a cross-sectional community survey conducted among residents from Hisayama Town, Japan, who were aged 40 to 79years old. A total of 1065 men (72.0% of the total population in the same age range) and 1381 women (79.0%) without renal failure (creatinine clearance of more than 30ml/min) underwent a comprehensive examination, including a 75g oral glucose tolerance test. The correlation analysis showed that serum insulin, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index were all negatively correlated with the reciprocal of serum creatinine level (P < 0.01), and alcohol intake was positively correlated (P < 0.05) in both sexes. High-density lipoprotein cholesterol and smoking habits were positively correlated (P < 0.05) in men. When the subjects were divided into quartiles based on the sum of fasting and two-hour postloading insulin levels, the averages of the reciprocal of serum creatinine were significantly lower in the fourth quartile (0.90 0.10 for men and 1.10 0. Continue reading >>

The Renal Metabolism Of Insulin

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 >>

Measuring Glomerular Filtration Rate Of The Kidneys With Insulin

Measuring Glomerular Filtration Rate Of The Kidneys With Insulin

In chronic kidney disease, the kidneys lose their ability to effectively filter waste products in the blood because of damage to the glomeruli of nephrons. Kidney function is determined by measuring glomerular filtration rate (GFR)--the volume of plasma that the kidneys filter through the glomeruli per unit time. The “gold standard” for measuring GFR is through the use of inulin, a carbohydrate produced by many plants, such as onions and garlic. Since inulin is not endogenous in humans, a specified mass must be injected into a person’s bloodstream in order to measure GFR. Inulin is useful as an indicator of GFR because the kidneys handle it in a unique way. Unlike most other substances in the blood, inulin is neither reabsorbed into the blood after filtration nor secreted through peritubular capillaries. Thus, the amount of inulin cleared through the urine is indicative of the amount of plasma filtered by the body’s glomeruli. GFR can be calculated using Equation 1. Equation 1 - Urine Concentration refers to the concentration of inulin in a sample of urine, Urine Flow refers to the amount of urine produced in a given time period, and Plasma Concentration refers to the concentration of inulin in blood plasma after intravenous injection. Researchers investigated how GFR was affected by furosemide, a diuretic medication that prevents sodium reabsorption in the loop of Henle. To do so, they observed the clearance rate of inulin in three groups of healthy cats that received different treatments. Their results are shown in Table 1. Table 1: Group A (control) received no treatment. Group B received 20 mL/h intravenous saline solution. Group C received 20 mL/h intravenous saline solution with 1 mg/h furosemide. Bumetanide is a diuretic drug that prevents reabsorption of Continue reading >>

Insulin Degradation: Progress And Potential

Insulin Degradation: Progress And Potential

V. Biological Role of Insulin Degradation VI. Insulin-IDE-Proteasome Interactions and Control of Protein Degradation THIS review is the third in a series of articles on insulin degradation in this journal ( 1 , 2 ). As such, it will focus on work published since the last report, but older studies will be discussed when appropriate. Interest in insulin degradation has long been confined to a limited audience. Recent information may stimulate more widespread attention since these data closely link insulin degradation and selected actions of the hormone. Insulin action is a complex process, which is not surprising considering the multiple cellular effects of insulin and the importance of the hormone for glucose, lipid, and protein turnover and for cell growth and differentiation. Insulin removal helps control the cellular response to the hormone by decreasing availability, but the degradative process may also be involved in mediating some aspects of insulin action ( 3 ). The insulin-degrading enzyme (IDE) has multiple cellular functions in addition to degradation, including binding and regulatory functions. IDE has regulatory functions for the activity of steroid receptors and proteasomes. Intracellular interactions of insulin with IDE may be involved in insulin control of cellular protein degradation and fat oxidation. Available data support an increased importance of insulin degradation and may open a new approach to understanding some actions of insulin. Insulin uptake and degradation is a feature of all insulin-sensitive tissues ( 4 6 ). At physiological concentrations, uptake is mediated primarily by the insulin receptor with a smaller contribution from nonspecific processes. At higher concentrations, nonreceptor processes assume greater importance. Insulin has a sho Continue reading >>

Renal Clearance

Renal Clearance

Definition : "Part of the total clearance due to renal excretion." Renal clearance mainly reflects the excretion of drug into the urine by the kidneys. Renal excretion of the drug is the neat result of glomerular filtration, active tubular secretion and tubular reabsorption. Rare drugs may undergo renal metabolism (e.g. insulin). The value of renal clearance is often used to identify the main mechanism involved in the renal excretion of the drug. Usually, if the renal clearance approximates the product of glomerular filtration rate by the unbound fraction of the drug, then filtration is thought to be the prominent mechanism. When renal clearance is less than the product of glomerular filtration rate by the unbound fraction, then renal reabsorption is assumed. When renal clearance is greater than the product of glomerular filtration rate by the unbound fraction, then secretion is thought to be present. However, all mechanisms may be operating, but one or two may dominate over the other masking their contribution. Variation of renal blood flow or of the unbound plasma drug concentration may more or less affect renal clearance, depending on the drug's renal extraction ratio . The drug's renal clearance can also be influenced by variation of its tubular secretion through a competitive or non-competitive inhibition or by a change in its passive reabsorption rate, e.g. through change of the urine pH (e.g. through ion trapping ). Furthermore, an increase of urine flow diminishes the time available for tubular reabsorption and therefore, can increase renal excretion of drugs. Usually, a drug's renal clearance is proportional to the patient's renal function. Whether a drug's dosing rate needs to be modified in patients with renal dysfunction depends on whether the drug is prima Continue reading >>

Insulin Resistance In Ckd

Insulin Resistance In Ckd

Insulin resistance is typically defined as decreased biologic action of insulin at its target organs (e.g., liver, skeletal muscles) for any given blood concentration of insulin. Clinically it usually presents with hyperinsulinemia, glucose intolerance, hyperglycemia, and dyslipidemia. Insulin resistance can be physiologic (e.g., in pregnancy) or pathologic. It may occur as a primary phenomenon contributing to the pathophysiology of type 2 diabetes or it may be secondary to other clinical disorders, and is often accompanied by cardiovascular sequels (1,2). There are a number of well established direct and indirect methods for the quantification of insulin resistance that vary in complexity. The Minimal Model provides an indirect measurement of insulin resistance on the basis of a frequently sampled intravenous glucose tolerance test. With respect to practicability, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is simpler. The HOMA-IR derives an estimate of insulin sensitivity from the mathematical modeling of fasting plasma glucose and insulin concentrations. Both methods have been intensively validated (3). Since the development of the hyperinsulinemic euglycemic clamp technique by DeFronzo et al. in 1979, impaired insulin-mediated glucose uptake to the skeletal muscles (a major target organ) could be directly quantified. It requires a high insulin blood level maintained by continuous infusion of insulin in order to suppress hepatic gluconeogenesis, followed by glucose infusion in order to preserve euglycemia (4). The advantage of this time- and resource-consuming technique, compared with the above methods, is that it can be used to measure tissue-specific insulin action and glucose uptake in skeletal muscles (3). The euglycemic clamp has since been Continue reading >>

The Renal Metabolism Of Insulin.

The Renal Metabolism Of Insulin.

Abstract 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 >>

Role Of The Kidney In Insulin Metabolism And Excretion

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 >>

Effect Of Insulin Resistance In Chronic Kidney Disease

Effect Of Insulin Resistance In Chronic Kidney Disease

1Imperial College Kidney and Transplant Institute, Hammersmith Hospital, Imperial College London, London, UK 2Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran *Corresponding Author: Andrew H Frankel Imperial College Kidney and Transplant Institute Hammersmith Hospital Imperial College London London, UK Tel: +98 912 188 1096 E-mail: [email protected] Citation: Frankel AH, Kazempour-Ardebili S (2016) Effect of Insulin Resistance in Chronic Kidney Disease. Endocrinol Metab Syndr 5:255. doi:10.4172/2161-1017.1000255 Copyright: © 2016 Frankel AH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Endocrinology & Metabolic Syndrome Abstract Insulin resistance accompanies many well-established cardiovascular risk factors, such as obesity, hypertension, dyslipidaemia and type 2 diabetes. Since cardiovascular disease (CVD) is the leading cause of death in patients with end stage renal disease (ESRD), insulin resistance is thought to play a role in the morbidity and mortality associated with ESRD. This paper reviews the available information on insulin resistance in patients with impaired kidney function as well as those on renal replacement therapy in the form of maintenance hemodialysis. Potential mechanisms for the dynamic changes in insulin resistance, which occur through the different stages of kidney disease, are also discussed. We hypothesize that stabilizing insulin sensitivity may have a positive effect on improving outcome in ESRD subjects Continue reading >>

Insulin And The Kidney

Insulin And The Kidney

Abstract Changes in renal function and structure are frequently observed in patients with diabetes mellitus. In the early phases of the disease, alterations in glomerular filtration rate, renal plasma flow, glomerular permeability and tubular capacity for glucose reabsorption occur. In the late stages of juvenile onset diabetes, renal failure is a common cause of death. For this reason, increasing attention is being paid to the possibility of long-term dialysis and renal transplantation in these patients. The kidneys play an important role in regulating insulin metabolism. The renal arteriovenous difference is approximately 30–45% and a linear relationship exists between the arterial insulin level and the renal arteriovenous concentration difference. The renal extraction of insulin is 200 ml/min in man, and it is estimated that 6–8 U are removed and degraded by the kidney in 24 h. The quantity of insulin in urine is small. However, its clearance is relatively constant over a wide range of serum concentrations and is 0.15–0.5 ml/min. The mean basal insulin excretion is 3.6 µU/mg creatinine, and a fourfold rise occurs following a glucose load. The urinary insulin values in neonates, children and patients with diabetes and renal failure are reviewed. In diabetic patients, progressive renal disease is accompanied by decreasing insulin requirements. In contrast, nondiabetic patients who develop renal failure frequently show abnormalities in carbohydrate metabolism, the commonest of which is a pseudodiabetic state. © 1975 S. Karger AG, Basel Article / Publication Details Continue reading >>

Management Of Diabetes Mellitus In Patients With Chronic Kidney Disease

Management Of Diabetes Mellitus In Patients With Chronic Kidney Disease

Abstract Glycemic control is essential to delay or prevent the onset of diabetic kidney disease. There are a number of glucose-lowering medications available but only a fraction of them can be used safely in chronic kidney disease and many of them need an adjustment in dosing. The ideal target hemoglobin A1c is approximately 7 % but this target is adjusted based on the needs of the patient. Diabetes control should be optimized for each individual patient, with measures to reduce diabetes-related complications and minimize adverse events. Overall care of diabetes necessitates attention to multiple aspects, including reducing the risk of cardiovascular disease, and often, multidisciplinary care is needed. Introduction Diabetes mellitus is a growing epidemic and is the most common cause of chronic kidney disease (CKD) and kidney failure. Diabetic nephropathy affects approximately 20–40 % of individuals who have diabetes [1], making it one of the most common complications related to diabetes. Screening for diabetic nephropathy along with early intervention is fundamental to delaying its progression in conjunction with providing proper glycemic control. Given the growing population that is now affected by diabetes and thus, nephropathy, knowledge regarding the safe use of various anti-hyperglycemic agents in those with nephropathy is of importance. In addition, attention to modification of cardiovascular disease (CVD) risk factors is essential. Altogether, knowledge regarding the prevention and management of diabetic nephropathy, along with other aspects of diabetes care, is part of the comprehensive care of any patient with diabetes. Review Recommendations for nephropathy screening in diabetes Patients with diabetes should be screened on an annual basis for nephropathy. I Continue reading >>

Renal Metabolism Of Insulin

Renal Metabolism Of Insulin

Abstract 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 >>

Inulin Clearance | Medicine | Britannica.com

Inulin Clearance | Medicine | Britannica.com

Inulin clearance, procedure by which the filtering capacity of the glomeruli (the main filtering structures of the kidney) is determined by measuring the rate at which inulin, the test substance, is cleared from blood plasma . Inulin is the most accurate substance to measure because it is a small, inert polysaccharide molecule that readily passes through the glomeruli into the urine without being reabsorbed by the renal tubules. The steps involved in this measurement, however, are quite involved; consequently, inulin is seldom used in clinical testing, although it is used in research. Creatinine clearance (q.v.) is the more common procedure used to assess renal function. The average rate at which substances are filtered out of the plasma (the glomerular filtration rate ) is about 75115 ml per minute for women and 85125 ml per minute for men. The rate decreases with age. It is markedly reduced in such conditions as acute glomerulonephritis (also called Bright disease ), which is characterized by inflammation of the small blood vessels that loop through the glomeruli. 2 references found in Britannica articles Corrections? Updates? Help us improve this article! Contact our editors with your feedback. Error when sending the email. Try again later. We welcome suggested improvements to any of our articles. You can make it easier for us to review and, hopefully, publish your contribution by keeping a few points in mind. Encyclopdia Britannica articles are written in a neutral objective tone for a general audience. You may find it helpful to search within the site to see how similar or related subjects are covered. Any text you add should be original, not copied from other sources. At the bottom of the article, feel free to list any sources that support your changes, so that w Continue reading >>

Lecture 12: Renal Clearance

Lecture 12: Renal Clearance

volume of plasma per minute needed to excrete the quantity of solute appearingin the urine in a minute If there were 1 mg of solute Z in 100 ml of plasma, and you found 0.5mg of Z appearing in the urine/ min, then the clearance of Z would = 50ml of plasma The hypothetical volume of plasma from which a substance is completelyremoved per minute in one pass thorough the kidney Figure 17.19 may help clarify or visualize these processes! PA = [solute] in arterial plasma (mg/100 ml plasma If in this example, 0.1 mg of solute appears in urine / min, in howmuch plasma was that 0.1 mg delivered if PA = 1.0 mg/100 ml ? In other words, that 0.1 mg of solute that appeared in the urine/minwas dissolved in 10 ml of plasma. Thus C = 10 mls/min. The E of a solute is equal to the fraction of the substance that is removedfrom the plasma in one pass through the kidney: SubstancePAPVUV X1.0 mg/100ml 0.8/1000.2 mg/ml1 ml/min Y1.00.30.71 Z1.00.90.11 To calculate RBF, first calculate C and E of substance with largestE GFR = C of solute which is ONLY FILTERED, e.g., inulin. WHY? See Figure 17.20 to see this concept. If Csolute = GFR, solute is only filtered If Csolute > GFR, solute is filtered and secreted If Csolute < GFR, solute is filtered and reabsorbed Figures 17.20 & 21 (a & b) are excellent representations ofthese concepts ! FF = fraction of plasma that is made into filtrate If Esolute = FF, solute is only filtered If Esolute > FF, solute is filtered and secreted If Esolute < FF, solute is filtered and reabsorbed Assume X from data set (above) is only filtered Calculate Amount of a solute filtered / min: Amount of a Solute Appearing in Urine / min For Solute Z, Amt Urine = 1 mg / ml x 1 ml / min = (20 ml/min x 1.0 / 100) 1 mg/ml x 1 ml/min) = (0.7 mg/ml x 1 ml/min) (1 mg/ 100 ml x 20 m Continue reading >>

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