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 >>
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 >>
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 >>
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 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 >>
