Physical And Chemical Properties Of 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

Insulin is a hormone, which contriutes to cell signalling. Its main function is the regulation of blood sugar levels, by causing the liver and muscles to increase uptake of glucose [1]. Insulin is produced from a single gene which codes for the peptide proinsulin; a precursor molecule. Mutations in this gene can result in a faulty protein; causing type 1 diabetes or a possible predisposition to type 2 diabetes [2][3]. Insulin regulates the blood glucose levels in different ways. It enhances the glucose transport at a cellular level by stimulation of the glucose transporter (GLUT) family. Insulin also has an effect on gene expression which is up or down regulated in the homeostasis process to maintain the optimum blood glucose levels. Insulin is released by the beta-cells (Islets of Langerhans) of the pancreas. Contents [hide] 1 History 2 Insulin stimulates glycogen synthesis 3 Origin of structure 4 Forming the structure of Insulin 5 Physical properties 6 Using recombinant DNA technology to produce active insulin molecules 7 References Insulin was first discovered in 1921 by Dr Frederick Banting and Charles Best after removing the pancreas from dogs and cattle[4]. Frederick Sanger's pioneering research led him to discover the amino acid sequence of the insulin in 1953 [5]. Insulin stimulates glycogen synthesis When blood sugar levels are high, insulin binds to a tyrosine kinase receptor. Binding of insulin triggers a phosphorylation cascade, preventing phosphorylation of glycogen synthase as this inactivates it's activity [6]. Insulin acts antagonistically to the hormone glucagon, which acts on glycogen storage in response to low blood sugar levels [7]. This serves as an effective homeostasis mechanism. Origin of structure Insulin (a globular protein) is extracted and pu Continue reading >>

Idegasp (insulin Degludec + Insulin Aspart) For The Management Of Type 2 Diabetes: Current Status

The co-formulation insulin degludec/insulin aspart (IDegAsp) contains insulin degludec (IDeg), a basal insulin, and the rapid-acting insulin aspart (IAsp). Its unique pharmacodynamic profile provides a stable basal insulin action over a 24-h period due to the flat, ultra-long effect of IDeg, combined with prandial control from IAsp, which is unaffected by the basal component. IDegAsp provides a distinct mealtime insulin peak effect and reduces the likelihood of postprandial glucose excursions. The phase 2 and 3 clinical trial program demonstrates that IDegAsp provides effective glycemic control with lower rates of hypoglycemia compared with the current standard of care for insulins. Compared with premixed insulin formulations, IDegAsp allows mealtime flexibility, enabling the time of injection to be adjusted to a different meal(s) on a daily basis to suit changing needs, and has the potential to improve adherence rates. IDegAsp offers a promising new insulin strategy for the treatment of type 2 diabetes. Although the underlying cause of type 2 diabetes mellitus (T2DM) remains controversial, effective early glycemic control, continued long-term, is a central element of the multiple-intervention approach to the management of T2DM [1]. Good glucose control can improve islet β-cell function and improve insulin sensitivity through reduction of glucose toxicity and, perhaps, lipotoxicity[2]. Microvascular complications, including nephropathy [3], retinopathy [4], neuropathy [5], and arterial damage [6], have been shown to be related to glycosylated hemoglobin (HbA1c) [4,7]. Better long-term glycemic control from diagnosis has been shown to decrease the occurrence of microvascular complications in patients with T2DM [8,9]. By contrast, intensive glycemic control in advanced T Continue reading >>

Soluble Insulin Analogs Combining Rapid- And Long-acting Hypoglycemic Properties – From An Efficient E. Coli Expression System To A Pharmaceutical Formulation

Abstract The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD). The SOD gene was used as a signal peptide to enhance the expression of insulin. SOD::INS was manufactured in the form of insoluble inclusion bodies. After cleavage of the fusion protein with trypsin, the released insulin analogs were refolded and purified by reverse-phase high performance liquid chromatography (RP-HPLC). Elongation of chain A, described here for the first time, considerably improved the stability of the selected analogs. Their identity was confirmed with mass spectrometric techniques. The biological activity of the insulin derivatives was tested on rats with experimental diabetes. The obtained results proved that the new analogs described in this paper have the potential to generate prolonged hypoglycemic activity and may allow for even less frequent subcutaneous administration than once-a-day. When applied, all the analogs demonstrate a rapid onset of action. Such a combination renders the proposed biosynthetic insulin unique among already known related formulations. Figures Citation: Mikiewicz D, Bierczyńska-Krzysik A, Sobolewska A, Stadnik D, Bogiel M, Pawłowska M, et al. (2017) Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties – From an Continue reading >>

Date Of Issue: 06/04/2015 Version1.0

SAFETY DATA SHEET according to the Global Harmonized System (and with all of the information required by the CPR) Page 1 of 31 SECTION 1.Identification Product identifier Catalog No. 635151 Product name Rat/Mouse Insulin ELISA Kit Rat Insulin Standards for ELISA (.25 ml) Relevant identified uses of the substance or mixture and uses advised against Identified uses Biochemical research/analysis Details of the supplier of the safety data sheet Company EMD Millipore Corporation | 290 Concord Road, Billerica, MA 01821, United States of America | General Inquiries: +1-978-715-4321 | Monday to Friday, 9:00 AM to 4:00 PM Eastern Time (GMT-5) Emergency telephone 800-424-9300 CHEMTREC (USA) +1-703-527-3887 CHEMTREC (International) 24 Hours/day; 7 Days/week SECTION 2. Hazards identification GHS-Labeling Other hazards None known. SECTION 3. Composition/information on ingredients Chemical nature Aqueous solution of inorganic and organic compounds. SECTION 4. First aid measures Description of first-aid measures Inhalation After inhalation: fresh air. Skin contact In case of skin contact: Take off immediately all contaminated clothing. Rinse skin with water/ shower. Eye contact After eye contact: rinse out with plenty of water. SAFETY DATA SHEET according to the Global Harmonized System (and with all of the information required by the CPR) Product number 635151 Version1.0 Product name Rat/Mouse Insulin ELISA Kit Rat Insulin Standards for ELISA (.25 ml) Page 2 of 31 Ingestion After swallowing: make victim drink water (two glasses at most). Consult doctor if feeling unwell. Most important symptoms and effects, both acute and delayed We have no description of any toxic symptoms. Indication of any immediate medical attention and special treatment needed No information available. SECTION 5 Continue reading >>

Section 1. Identification 1.1. Product Identifier(s)

Monobind, Inc. SAFETY DATA SHEET Monobind Inc. ISO 13485 & 9001 Certified Company Name: Rapid Insulin AccuBindÂ® ELISA Test System Description: AccuBindÂ® ELISA Microwells Code: 5625-300 Characteristics: Microplate Enzyme Immunoassay, Colorimetric 1.2. Relevant identified uses of the substance or mixture and uses advised against Quantitative determination of Insulin concentration in human serum by a microplate enzyme immunoassay, colorimetric. For in vitro diagnostic use only. Not for internal or external use in humans or animals. 1.3. Details of the supplier of the safety data sheet Manufacturer/Importer: Manufacturer Name or commercial name: Monobind Inc. Registered office: 100 North Pointe Drive, Lake Forest, California 92630, USA Telephone number: +1.949.951.2665 Fax number: +1.949.951.3539 Email: [email protected] FDA Established Registration number: 2020726 1.4. Emergency telephone number +1.949.951.2665 (Hours: 8 am-5 pm PST, Monday-Friday) SECTION 2. HAZARD(S) IDENTIFICATION 2.1. Classification of the substance or mixture None 2.2. Label elements None 2.3. Other hazards None SECTION 3. COMPOSITION/INFORMATION ON INGREDIENTS 3.1. Substances and/or Mixtures All concentrations of potentially hazardous substances or mixtures are below the specific concentration limits and M-factors for hazardous identification. As preparations, the product components are not classified as hazardous. The following substance exceeds the generic cut-off value and is listed with its concentration level. At this concentration level, the substance is not hazardous. See section 16 for definitions for all risk and hazards classifications. 3.1.1. Rapid Insulin Calibrators (A-F) N/A 3.1.2. Rapid Insulin Enzyme Reagent N/A 3.1.3. Streptavidin Coated Plate N/A 3.1.4. Substrate Reagent N/A 3 Continue reading >>

Aggregation Of Insulin At The Interface [2014]

Insulin has so far been the most important pharmaceutical peptide for diabetes treatment, assisting to regulate carbohydrate and fat metabolism in patients. However, aggregation of insulin occurs readily in almost every biopharmaceutical process, ranging from production, purification, storage, transportation, delivery, to in vivo utilization at the terminal. As interfaces and surfaces are ubiquitous in each process and strongly influence physical/chemical properties of insulin, it is necessary and fundamentally important to investigate the aggregation of insulin at various interfaces, such as aqueousâsolid interface, waterâoil interface, and airâwater interface. The objective of this article is to briefly summarize recent progress on insulin aggregation at different interfaces, with special focus on the airâwater interface using the Langmuir monolayer technique. Continue reading >>

Glucose-responsive Insulin By Molecular And Physical Design

The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach. Corrected online 24 November 2017 In the version of this Perspective originally published, the affiliations for authors Zhen Gu and Sanjoy Dutta were not correct, they should have read: Zhen Gu3,4,5, Sanjoy Dutta6. 3Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695, USA. 4Pharmacoengineering and Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. 5Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. 6JDRF International, New York, New York 10004, USA. Royo, M., Alsina, Continue reading >>

Human Insulin Elisa

Safety Information The RIS006R Human Insulin ELISA is an immunoenzymetric assay for the measurement of human Insulin in serum. For professional use only. Users should have a thorough understanding of the Product Data Sheet prior to their use of this kit. Kit Components: A) Microtiterplate B) Anti-INS-HRP Conjugate C) Zero Calibrator D) Calibrator 1 to 5 E) Controls 1 and 2 F) Wash Solution G) Chromogen: TMB H) Stopping reagent Stopping reagent containing hydrochloric acid is a hazardous mixture according to CLP Regulation (EC) as amended. Safety Data Sheet for Hydrochloric Acid < 5% according to actual Regulations (EC/EU) is attached. The other components do not contain any hazardous mixture according to CLP Regulation (EC) as amended. ï¿½ ï¿½ ï¿½ MATERIAL SAFETY DATA SHEET in accordance with Regulation (EC) No. 1907/2006 of the European Parliament and the Council (REACH) and Commission Regulation (EU) No. 830/2015 Hydrochloric Acid < 5% Date of issue: 30.7.2015 Supersedes date: Page 1 of 7 ï¿½ SECTION 1 IDENTIFICATION OF THE PREPARATION AND OF COMPANY/UNDERTAKING 1.1 Product identifier Trade name: Hydrochloric Acid < 5% Additional identification: solution with hydrochloric acid concentration < 5% w/w 1.2 Relevant identified uses of the substance or mixture and uses advised against Stop solution for the ELISA kit. 1.3 Details of the supplier of the safety data sheet BioVendor - LaboratornÃ medicÃna a.s. KarÃ¡sek 1767/1 621 00 Brno Czech Republic Identification number: 63471507 Tel: +420 549 124 185 E-mail: [email protected] 1.4 Emergency telephone number Toxicology information centre, Na BojiÅ¡ti 1, 128 21 Prague, Czech Republic, Tel: +420 224 919 293 or +420 224 915 402 (non-stop service). SECTION 2 HAZARDS IDENTIFICATION 2.1 Classification of the su Continue reading >>

Nanoparticle Chain Formation On Functional Surfaces Using Insulin Fibrils As A Structure Directing Agent

Nanoparticles exhibit unique size-dependent physical and chemical properties which may be further modified by controlling their spatial arrangement. For example, when metallic nanoparticles are placed sufficiently close together, near-field coupling between surface plasmons occurs which can lead to enhancement. In this report, insulin fibrils were used as a structure directing agent to attach Au nanoparticles to wafer-grade polished glass and ITO substrates, and to attach Au and CdSe nanoparticles to PDMS substrates. The nanoparticles adhered preferentially to the insulin fibrilsvia electrostatic interactions. This method provides a general approach for aligning nanoparticles into chains on functional surfaces for applications such as optical waveguides. Continue reading >>

Physicochemical Properties Of P-carboxyphenylazoinsulins1

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Cinnamon's Infection and Diabetes-Fighting Properties Revealed

The Purification And Some Properties Of Insulin

1. A scheme of purification by fractional precipitation of insulin with alcohol has been presented. The procedure yields a product as potent as crystalline insulin. 2. The solubility of insulin and associated inert protein in alcoholic solution has been described. Neutral salts increase the solubility at the pH of minimum solubility. The increase is dependent upon the concentration of the neutral salts present in the alcoholic system. Sulphates displace the pH of minimum solubility to a region quite acid to isoelectric point whereas chlorides and acetates do not alter markedly the precipitation zone. Possibly displacement by chlorides is to a region slightly alkaline to the isoelectric point. 3. Preparations of different physiological activity have been analyzed for tyrosine and tryptophane. Three of the four methods employed showed tryptophane absent in crystalline insulin. The highly potent insulin obtained by fractional precipitation with alcohol carried from less than 0.1 to 0.56 per cent tryptophane. 4. A comparison of procedures for crystallization of insulin was made. Abel's brucine-pyridine-ammonium acetate method was considered to be the most satisfactory for the majority of samples. New modifications were described, based upon the conception that crystallization will occur in systems in which insulin is held in solution at its isoelectric by agents which do not cause chemical change. All methods yield crystalline insulin of essentially the same activity. 5. Insulin was crystallized from material which has been previously coagulated by heat in acid solution. Its potency was essentially the same as crystalline insulin prepared from uncoagulated insulin. 6. The influence of purity, pH and temperature upon the rate of coagulation was studied in some detail. No con Continue reading >>

Insulin Human

Class: Insulins ATC Class: A10AB01 VA Class: HS501 Molecular Formula: C257H383N65O77S 6 CAS Number: 11061-68-0 Brands: HumuLIN, HumuLIN 70/30, HumuLIN 70/30 Pen, HumuLIN 50/50, HumuLIN L, HumuLIN N, HumuLIN R, HumuLIN U Ultralente, NovoLIN, NovoLIN 70/30, NovoLIN 70/30 Innolet, NovoLIN 70/30 PenFill, NovoLIN N, NovoLIN R Introduction Antidiabetic agent; a biosynthetic protein that is structurally identical to endogenous insulin secreted by the beta cells of the human pancreas.1 2 3 5 6 38 53 65 71 75 76 Available as short-acting, rapid-acting, intermediate-acting, or long-acting insulins.1 2 3 5 6 38 53 65 71 75 76 Uses for Insulin Human Diabetes Mellitus Replacement therapy for the management of diabetes mellitus.5 6 7 8 12 113 Human insulin manufactured using recombinant DNA technology is replacing pork insulin; future availability of animal insulins is uncertain.103 Insulin is required in all patients with type 1 diabetes mellitus, and mandatory in the treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic states. Also used in patients with type 2 diabetes mellitus when weight reduction, proper dietary regulation, and/or oral antidiabetic agents have failed to maintain satisfactory glycemic control in both the fasting and postprandial state. Diet should be emphasized as the primary form of treatment when initiating therapy for patients with type 2 diabetes mellitus who do not have severe symptoms; caloric restriction and weight reduction are essential in obese patients. The American Diabetes Association (ADA) and many clinicians recommend the use of physiologically based, intensive insulin regimens (i.e., 3 or more insulin injections daily with dosage adjusted according to the results of multiple daily blood glucose determinations [e.g., at least 4 times d Continue reading >>

Chemical Properties Of The Functional Groups Of Insulin.

The method of competitive binding [Kaplan, Stevenson & Hartley (1971) Biochem. J. 124, 289-299] with 1-fluoro-2,4-dinitrobenzene as the labelling reagent [Duggleby & Kaplan (1975) Biochemistry 14, 5168-5175] was used to determine the chemical properties, namely pK and reactivity, of the amino groups, the histidine residues and the tyrosine residues of the dimeric form of pig zinc-free insulin at 20.0 degrees C. The N-terminal glycine residue of the A-chain has a pK of 7.7 and a slightly higher than normal reactivity. The N-terminal phenylalanine residue of the B-chain has a pK of 6.9 and is approximately an order of magnitude more reactive than a corresponding amino group with the same pK value. The lysine epsilon-amino group has an unusually low pK of 7.0 but has approximately the expected reactivity of such a group. In the case of the two histidine and four tyrosine residues only the average properties of each class were determined. The histidine residues have a pK value of approx. 6.6, but, however, their reactivity is at least an order of magnitude greater than that of a free imidazole group. The tyrosine residues have a pK value of approx. 10, but their average reactivities are substantially less than for a free phenolic group. At alkaline pH values above 8 the reactivity of all the functional groups show sharp discontinuities, indicating that insulin is undergoing a structural change that alters the properties of these groups. 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 (1017K), 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 references f Continue reading >>

What Is Insulin? What Is The Glycemic Index?

When it comes to our hormones and our diets, we sometimes feel overwhelmed since there is so much information. Allow me to provide some explanation regarding the hormone insulin and to define the Glycemic Index Diet. Insulin is an important hormone created by the pancreas. Insulin lets the body use sugar (glucose) from carbohydrates in the foods the body consumes for energy or for storage. Insulin also helps prevent the blood sugar from increasing too much or decreasing too little. It functions as a “key,” unlocking cells for sugar to enter. Sugar is needed for energy but it cannot directly travel to most cells. After food is digested and the blood sugar level increases, cells in the pancreas release insulin into your bloodstream. (“What is insulin?” Amy Hess-Fischl MS, RD, LDN, BC-ADM, CDE) Those who have Type 1 diabetes cannot produce insulin since the beta cells in the pancreas are harmed or completely destroyed. People with Type 2 diabetes do not always respond well to insulin but can sometimes improve their condition with diet, exercise and oral medications. Once again, diet is absolutely crucial! When the blood sugar is closely monitored, there is a decrease in the risk of getting diabetes complications such as heart disease, eye and kidney disease. Please remember the type of diet highly recommended by experts is the anti-inflammation diet and consuming low glycemic index foods. Now, let’s review the Glycmic Index diet. Using the glycemic index assists individuals with diabetes to better control their blood sugar levels. The glycemic index diet focuses on carbohydrates. Most of us are aware that certain foods such as white rice, white flour, cookies and brown potatoes rapidly increase our blood sugar level. But let’s get more specific. Below is a list Continue reading >>