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Chemistry Of Insulin

Coordination Chemistry And Insulin-enhancing Behavior Of Vanadium Complexes With Maltol C6h6o3 Structural Isomers

Coordination Chemistry And Insulin-enhancing Behavior Of Vanadium Complexes With Maltol C6h6o3 Structural Isomers

Medicinal Inorganic Chemistry Group, Department of Chemistry, and Faculty of Pharmaceutical Sciences, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada Synopsis Vanadium(III, IV, V) ions are complexed to the structural isomers of maltol, allomaltol, and isomaltol; the potentially tetradentate aminopyrone H2(en(ama)2) is chelated to vanadium(IV). All complexes were completely characterized including X-ray crystal structure analyses for VO(ima)2 and V(ima)3. Stability constants of the V(IV)−isomaltol system are reported herein for the first time and compared to those of the other two C6H6O3 isomers. The insulin-enhancing ability of these vanadium compounds is also reported. Abstract Syntheses of vanadium complexes using the naturally occurring ligands isomaltol (Hima) and allomaltol (Hama), as well as a newly synthesized, potentially tetradentate diaminodipyrone [H2(en(ama)2], are reported. Complete characterization of the resulting compounds [trans-VO(ima)2(H2O), VO(ama)2, V(ima)3, V(ama)3 and VO(en(ama)2)], including X-ray crystallography analyses for trans-VO(ima)2(H2O) and V(ima)3, are presented herein. Potentiometric titrations (25°C, I = 0.16 M NaCl) were used to measure stability constants in the V(IV)−Hima system; these data were compared to previous data collected on the V(IV)−L (L = Hma, Hama) systems. The in vivo efficacy of these compounds to lower the blood glucose levels of STZ-diabetic rats was tested; all but VO(en(ama)2) produced significant decreases in plasma glucose levels. The results were compared to those of the benchmark compound BMOV [VO(ma)2, bis(maltolato)oxovanadium(IV)], a known insulin-enhancing agent. Continue reading >>

Molecule Of The Month - July 2010

Molecule Of The Month - July 2010

Computer-generated image of six insulin molecules assembled in a hexamer (from Ref.[1]). 3D structure file INSULIN The hormone that converts sugar in the blood into asource of energy for our body's metabolic processes "Laughter is the best medicine- unless you're diabetic, then insulin comes pretty high on the list" - Jasper Carrott [3] So, what is a hormone, really? Hormones are chemical components that are produced in one part of the body and function at an entirely different one [4]. They include proteins, peptides and lipids, existing usually as precursor molecules [5]. In addition hormones have various functions such as the regulation of metabolism and its development. A major role is to act as messengers and carry information around tissues in the body by binding receptors on cell surfaces or within a cell [5]. Receptors are proteins on cell surfaces or within them with available sites for the signalling ligand molecule to bind on. The receptor's major role is to act as the conductor for hormones and drugs to reach the body and the target they require. One of the main peptide hormones studied through years due to its importance and necessity is insulin, whose structure, synthesis and function are discussed further below. What does insulin do? Insulin is a hormone that is central to regulating glucose metabolism in the body to produce energy. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, which it then converts to glycogen which is stored in the liver and muscle. When insulin is absent, glucose is not taken up by body cells and the body begins to use fat as an energy source. What about insulin's structure? It seems to be very complicated. Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight Continue reading >>

The Chemistry Of Insulin Apart

The Chemistry Of Insulin Apart

Introduction Insulin is an amazing drug that is used to help diabetic people live as healthy lives as they can. The drug is injected by syringe after a diabetic person eats, replacing the natural process that occurs in nondiabetic people, where insulin is transferred from the pancreas to the bloodstream into cells to take the new sugar and use it for energy or later use. Novolog, or insulin aspart, a specific type and brand of insulin, works in its own specific way. Insulin aspart is called rapid-acting insulin, in which the composition is manipulated from normal insulin to make it work faster. Insulin aspart starts to work 15 min after it is injected. I chose to do insulin, specifically insulin aspart, because I have been a type 1 diabetic for 8 years and use it everyday. Before researching, I was interested in how close man-made insulin was to human insulin, and it turns out that they are almost identical, being only one amino acid different. Insulin has always fascinated me. Insulin has affected my life in great ways. It is the single reason that I am still alive and healthy. Without it, especially insulin aspart, I do not even want to image what my life would look like, or what could ever take its place. Composition of ... C256H381N65O79S6 100 Units/mL Zinc = 19.6 mcg/mL Disodium hydrogen phosphate dihydrate = 1.25 mg/mL m-Cresol = 1.72 mg/mL Phenol = 1.5 mg/mL Glycerin = 16 mg/mL Sodium Chloride = .58 mg/mL Water = remainder for injection Main Chemicals, Compounds, Components Glycerin = C3H8O3 Glycerin is a simple sugar alcohol compound that is used in insulin as an isotonicity agent, or thing that makes insulin flow inside a body, like water. It is also a humectant, which means that it keeps insulin in liquid form for longer. Glycerin is a very important part of i Continue reading >>

Insulin

Insulin

A protein with an impressive roster of ‘firsts’: Anna Lewcock introduces insulin Meera Senthilingam This week, a first for protein synthesis, resulting in a compound saving the lives of millions worldwide. Anna Lewcock… Anna Lewcock The year is 1922. Fourteen-year-old Leonard Thompson is at death’s door. Weighing just four and half stone, he is admitted to hospital slipping into a coma. In desperation, his father allows doctors to inject Leonard with a new drug never before tested on humans. But his son suffers an allergic reaction, and remains critically ill. Two weeks later, the doctors try again with a purer form of the extract. This time, the results are staggering. Leonard quickly regains his strength, his appetite, and his life. All thanks to a modest molecule called insulin. Insulin is a peptide hormone produced by the pancreas. But in the 371 million people worldwide who suffer from diabetes, something is amiss. In type 1 diabetes, the pancreas doesn’t produce any insulin. In the more common type 2, it doesn’t produce enough or the insulin it does produce doesn’t work properly. Insulin unlocks the body’s cells, allowing glucose in to be used for energy. With the body unable to metabolise glucose, it builds up in the blood leading to dangerously high blood sugar levels, and if left untreated, can lead to devastating health complications. Before the discovery of insulin, it was essentially a death sentence: patients with Type 1 diabetes were put on a starvation diet and given just months to live. Diabetes has been recognised as an illness for thousands of years. But it wasn’t until the late 1800s that researchers suggested we should look to the pancreas for a substance responsible for metabolic control. It then took until the 1920s for it to be i Continue reading >>

Chemistry And Insulin-like Properties Of Vanadium(iv) And Vanadium(v) Compounds1

Chemistry And Insulin-like Properties Of Vanadium(iv) And Vanadium(v) Compounds1

Get rights and content The chemistry of vanadium compounds that can be taken orally is very timely since a vanadium(IV) compound, KP-102, is currently in clinical trials in humans, and the fact that human studies with inorganic salts have recently been reported. VO(acac)2 and VO(Et-acac)2 (where acac is acetylacetonato and Et-acac is 3-ethyl-2,4-pentanedionato) have long-term in vivo insulin mimetic effects in streptozotocin induced diabetic Wistar rats. Structural characterization of VO(acac)2 and two derivatives, VO(Me-acac)2 and VO(Et-acac)2, in the solid state and solution have begun to delineate the size limits of the insulin-like active species. Oral ammonium dipicolinatooxovanadium(V) is a clinically useful hypoglycemic agent in cats with naturally occurring diabetes mellitus. This compound is particularly interesting since it represents the first time that a well-characterized organic vanadium compound with the vanadium in oxidation state five has been found to be an orally effective hypoglycemic agent in animals. Continue reading >>

Insulin

Insulin

Insulin is a small peptide (protein) consisting of fifty-one amino acids synthesized and stored within the pancreas, an organ situated behind the stomach. The protein itself consists of two chains, denoted A and B, linked by disulfide (sulfur-sulfur) bridges between cysteine residues (see Figure 1). Insulin is a hormone, a chemical transported in the blood that controls and regulates the activity of certain cells or organs in the body. When blood sugar levels rise following a meal, the pancreas is stimulated to release insulin into the bloodstream. In order for tissues to absorb glucose from the blood, they must first bind insulin. Glucose metabolism is necessary for cell growth and energy needs associated with cell function. When insulin binds to receptors on cell membranes, glucose transporter proteins are released from within the cell to the surface of the cell membrane. Once on the exterior surface of cells, glucose transporters can carry sugar from the blood into the tissue where it is metabolized. Without insulin, cells cannot absorb glucose and effectively starve. A deficiency in insulin production results in a condition called diabetes mellitus. Approximately 6.2 percent of the population in the United States is affected with diabetes. Type 1 diabetics account for 10 percent of those individuals suffering from diabetes mellitus. It is also known as juvenile diabetes and generally develops in young people, typically between the ages of ten and fifteen years, as a result of an autoimmune disorder. Why the body's immune system turns on itself, attacking and destroying beta cells, the pancreatic cells in which insulin is synthesized, is not clear. The unfortunate consequence is insulin deficiency. The majority of individuals afflicted with diabetes mellitus suffer f Continue reading >>

Insulin: Discovery And Controversy

Insulin: Discovery And Controversy

During the first two decades of the 20th century, several investigators prepared extracts of pancreas that were often successful in lowering blood sugar and reducing glycosuria in test animals. However, they were unable to remove impurities, and toxic reactions prevented its use in humans with diabetes. In the spring of 1921, Frederick G. Banting, a young Ontario orthopedic surgeon, was given laboratory space by J.J.R. Macleod, the head of physiology at the University of Toronto, to investigate the function of the pancreatic islets. A student assistant, Charles Best, and an allotment of dogs were provided to test Banting’s hypothesis that ligation of the pancreatic ducts before extraction of the pancreas, destroys the enzyme-secreting parts, whereas the islets of Langerhans, which were believed to produce an internal secretion regulating sugar metabolism, remained intact. He believed that earlier failures were attributable to the destructive action of trypsin. The name “insuline” had been introduced in 1909 for this hypothetic substance. Their experiments produced an extract of pancreas that reduced the hyperglycemia and glycosuria in dogs made diabetic by the removal of their pancreases. They next developed a procedure for extraction from the entire pancreas without the need for duct ligation. This extract, now made from whole beef pancreas, was successful for treating humans with diabetes. Facilitating their success was a development in clinical chemistry that allowed blood sugar to be frequently and accurately determined in small volumes of blood. Success with purification was largely the work of J.B. Collip. Yield and standardization were improved by cooperation with Eli Lilly and Company. When the Nobel Prize was awarded to Banting and Macleod for the discove Continue reading >>

Insulin Chemistry And Functions

Insulin Chemistry And Functions

Insulin Biosynthesis, Secretion, and Action Biosynthesis Insulin is produced in the beta cells of the pancreatic islets. It is initially synthesized as a single-chain 86-amino-acid precursor polypeptide, preproinsulin. Subsequent Proteolytic processing removes the amino terminal signal peptide, giving rise to proinsulin. Proinsulin is structurally related to insulin-like growth factors I and II, which bind weakly to the insulin receptor. Cleavage of an internal 31-residue fragment from proinsulin generates the C peptide and the A (21 amino acids) and B (30 amino acids) chains of insulin, which are connected by disulfide bonds (Figure-1)The mature insulin molecule and C peptide are stored together and co secreted from secretory granules in the beta cells. Because the C peptide is cleared more slowly than insulin, it is a useful marker of insulin secretion and allows discrimination of endogenous and exogenous sources of insulin in the evaluation of hypoglycemia. Secretion Glucose is the key regulator of insulin secretion by the pancreatic beta cell, although amino acids, ketones, various nutrients, gastrointestinal peptides, and neurotransmitters also influence insulin secretion. Glucose levels > 3.9 mmol/L (70 mg/dL) stimulate insulin synthesis, primarily by enhancing protein translation and processing. Glucose stimulation of insulin secretion begins with its transport into the beta cell by the GLUT2 glucose transporter. Glucose phosphorylation by glucokinase is the rate-limiting step that controls glucose-regulated insulin secretion. Further metabolism of glucose-6-phosphate via Glycolysis generates ATP, which inhibits the activity of an ATP-sensitive K+ channel. This channel consists of two separate proteins: one is the binding site for certain oral hypoglycemic (e.g., Continue reading >>

What Is Insulin?

What Is Insulin?

Insulin is a hormone that is important for metabolism and utilization of energy from the ingested nutrients - especially glucose. Insulin chemistry and etymology Insulin is a protein chain or peptide hormone. There are 51 amino acids in an insulin molecule. It has a molecular weight of 5808 Da. Insulin is produced in the islets of Langerhans in the pancreas. The name insulin comes from the Latin ''insula'' for "island" from the cells that produce the hormone in the pancreas. Insulin's structure varies slightly between species of animal. Both porcine (from pigs) and bovine (from cows) insulin are similar to human insulin but porcine insulin resembles human insulin more closely. What does insulin do? Insulin has several broad actions including: It causes the cells in the liver, muscle, and fat tissue to take up glucose from blood and convert it to glycogen that can be stored in the liver and muscles Insulin also prevents the utilization of fat as an energy source. In absence of insulin or in conditions where insulin is low glucose is not taken up by body cells, and the body begins to use fat as an energy source Insulin also controls other body systems and regulates the amino acid uptake by body cells It has several other anabolic effects throughout the body as well Secretion of insulin Insulin is synthesized in significant quantities only in beta cells in the pancreas. It is secreted primarily in response to elevated blood concentrations of glucose. Insulin thus can regulate blood glucose and the body senses and responds to rise in blood glucose by secreting insulin. Other stimuli like sight and taste of food, nerve stimulation and increased blood concentrations of other fuel molecules, including amino acids and fatty acids, also promote insulin secretion. What happens wh Continue reading >>

Insulin, Chemical Structure And Metabolism

Insulin, Chemical Structure And Metabolism

Insulin is a polypeptide hormone formed, after elimination of C peptide by hydrolysis, of two chains of 21 and 30 amino acids, connected by two disulfide bridges. It is secreted by the ß cells of the islets of Langerhans of the pancreas and exerts an hypoglycemic action. It belongs to the group of peptides called IGF (insulin like growth factors) or somatomedins. Biosynthesis Insulin is produced in beta cells which constitute 75% of the islets of Langerhans of the pancreas. Alpha cells secrete glucagon, delta cells somatostatin. Insulin is synthesized in the form of a single polypeptide chain, preproinsulin which is transformed into proinsulin which, itself, catalyzed by proteases called furines, gives insulin and C peptide (C for connecting, because connecting the two chains A and B). Bound to two zinc atoms, insulin is stored in granules as a polymer, probably a hexamer. Secretion Insulin, as well as C peptide, are released by exocytosis into the portal venous system which leads it directly to the liver, which takes up nearly 50%. The remainder of insulin is distributed throughout the body. With a basal secretion of approximately 40 microgram/h under fasting conditions, there are increases of secretion linked to meals. To these slow variations are superimposed peaks of pulsatile secretion. The aim of the treatments by exogenous insulin is to approach the physiological curve of secretion. The principal stimulant of insulin secretion is glucose; it elicits a biphasic release: an immediate effect of short duration and a sustained effect. The cells of the islets are connected by tight junctions, which allow the transfer of ions, of metabolites, secondary messengers from one cell to another, and thus play an important part in synchronizing the secretions. The stimulation Continue reading >>

Facts About Diabetes And Insulin

Facts About Diabetes And Insulin

Diabetes is a very common disease, which, if not treated, can be very dangerous. There are two types of diabetes. They were once called juvenile-onset diabetes and adult diabetes. However, today we know that all ages can get both types so they are simply called type 1 and type 2 diabetes. Type 1, which occurs in approximately 10 percent of all cases, is an autoimmune disease in which the immune system, by mistake, attacks its own insulin-producing cells so that insufficient amounts of insulin are produced - or no insulin at all. Type 1 affects predominantly young people and usually makes its debut before the age of 30, and most frequently between the ages of 10 and 14. Type 2, which makes up the remaining 90 percent of diabetes cases, commonly affects patients during the second half of their lives. The cells of the body no longer react to insulin as they should. This is called insulin resistance. In the early 1920s, Frederick Banting, John Macleod, George Best and Bertram Collip isolated the hormone insulin and purified it so that it could be administered to humans. This was a major breakthrough in the treatment of diabetes type 1. Insulin Insulin is a hormone. Hormones are chemical substances that regulate the cells of the body and are produced by special glands. The hormone insulin is a main regulator of the glucose (sugar) levels in the blood. Insulin is produced in the pancreas. To be more specific, it's produced by the beta cells in the islets of Langerhans in the pancreas. When we eat, glucose levels rise, and insulin is released into the bloodstream. The insulin acts like a key, opening up cells so they can take in the sugar and use it as an energy source. Sugar is one of the top energy sources for the body. The body gets it in many forms, but mainly as carbohydr Continue reading >>

Insulin Biosynthesis, Secretion, Structure, And Structure-activity Relationships

Insulin Biosynthesis, Secretion, Structure, And Structure-activity Relationships

Insulin Biosynthesis, Secretion, Structure, and Structure-Activity Relationships Michael Weiss, Donald F Steiner, M.D., and Louis H Philipson, M.D., Ph.D. Professor, Biochemistry & Molecular Biology, Department of Medicine, Howard Hughes Medical Institute, University of Chicago, Chicago, IL, [email protected] Professor of Endocrinology, Department of Medicine and Committee on Cell Physiology, University of Chicago, Chicago, IL, [email protected] The structure of insulin contains determinants of foldability, trafficking, self-assembly, and receptor binding. Insulin is the biosynthetic product of a single-chain precursor, preproinsulin, whose proteolytic processing is coupled to trafficking between cellular compartments. The connecting (C) domain of proinsulin is removed by a specialized set of endoproteases and a carboxypeptidase activity, acting mainly within maturing secretory granules. Insulin is stored as microcrystalline arrays of zinc insulin hexamers within specialized glucose-regulated secretory vescicles. Regulation of insulin secretion is coupled to metabolism and electrophysiologic events involving plasma membrane depolarization and calcium-ion homeostasis. The insulin receptor is a transmembrane protein containing an extracellular hormone-binding domain and intracellular tyrosine kinase domain. Binding of insulin to the insulin receptor (an () 2 dimer) is mediated by side chains in both the A- and B chains of insulin. The primary hormone-binding site (Site 1) in the extracellular domain of the insulin receptor contains the L1 -helix of one -subunit and the C-terminal CT -helix of the other -subunit. Dominant mutations in the insulin gene cause monogenic syndromes of diabetes mellitus, prominently including permanent neonatal-onset diabetes, Continue reading >>

Understanding The Chemistry Of Insulin

Understanding The Chemistry Of Insulin

Editor’s Note: This article was originally written by patient expert Anna. Even though I take insulin every day, I never considered the chemistry of insulin until I began working in a chemistry research lab at college. Prior to this year, the sum of my knowledge about insulin probably came from one of those “Newly Diagnosed” pamphlets that the doctors were so quick to administer in the first few appointments. I knew that, like all Type I diabetics, my body no longer produced insulin. Insulin, I learned, is the key hormone needed to regulate energy and glucose metabolism. Insulin is a polypeptide hormone, which means that is it composed of two protein strands. Proteins are molecules composed of smaller subunits called amino acids, which join together through a peptide bond. Long chains of amino acids fold in a very particular way, forming mature and functional proteins. Proteins have many important functions in the body, including structure, immune defense, and transport. Certain proteins function as hormones, as in the case of insulin. Insulin is important in regulating levels of blood glucose and providing energy to all tissues. In the body, dietary carbohydrates are broken down into a simple sugar, glucose, which is transported in the blood. In response to the spike in blood glucose levels, the pancrease releases insulin as part of a negative feedback system to maintain homeostasis. Insulin lowers blood glucose levels by facilitating the sugar molecules from carbohydrates to leave the bloodstream and enter energy-starved cells. The specific cells that produce insulin are the β-cells of the islets of Langerhans in the pancreas. A mature insulin molecule contains two chains- an A and a B chain, held together by disulfide bonds. In the β-cells, insulin is fir Continue reading >>

Insulin Chemistry | Springerlink

Insulin Chemistry | Springerlink

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 92) Major aims of insulin chemistry are the large-scale production of the hormone for the treatment of diabetes mellitus as well as laboratory-scale syntheses of analogs for structure-function studies, of radioactive tracers, and of tailormade special derivatives. Further, one should include the detection and isolation of new native insulins and related compounds. The total synthesis, accomplished 25 years ago by the groups of ZAHN (MEIENHOFER et al. 1963), KATSOYANNIS (1964), and in China marked the advent of a new era in pep tide and protein chemistry. Remarkable progress has since been achieved through refinement of synthetic and semisynthetic procedures, the advances in recombinant DNA techniques, and high pressure liquid chromatography (HPLC). Insulin ReceptorHigh Pressure Liquid ChromatographyHuman InsulinInsulin AnaloguePorcine Insulin These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. This is a preview of subscription content, log in to check access Unable to display preview. Download preview PDF. Ambrosius D, Bala-Mohan S, Behrendt C, Schfer K, Schttler A, Brandenburg D (1987) New photoreactive derivatives of insulin for affinity-labelling of the insulin receptor. In: Theodoropoulos D (ed) Peptides 1986. De Gruyter, New York, pp 521523 Google Scholar Assoian RK, Thomas NE, Kaiser ET, Tager HS (1982) [LeuB24]Insulin and [AlaB24]insulin: altered structures and cellular processing of B24-substituted insulin analogs. Proc Natl Acad Sci USA 79:51475151 PubMed Google Scholar Bahrami S, Zahn H, Brandenburg D, Machulla H-J, Dutschka K (1980) [B1-125I-Desaminotyrosine] insulin a novel homog Continue reading >>

Insulin

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 >>

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