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Chemistry of Pancreatic Polypeptide Hormone with Official Preparation

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Chemistry of Pancreatic Polypeptide Hormone with Official Preparation wjpmr, 2020,6(9), 102-114 SJIF Impact Factor: 5.922 WORLD JOURNAL OF PHARMACEUTICAL Review Article Arpan et al. World Journal of Pharmaceutical and Medical Research AND MEDICAL RESEARCH ISSN 2455-3301 www.wjpmr.com Wjpmr CHEMISTRY OF PANCREATIC POLYPEPTIDE HORMONE WITH OFFICIAL PREPARATION Arpan Chanda*1, Arunava Chandra Chandra2, Dr. Dhrubo Jyoti Sen2 and Dr. Dhananjoy Saha3 1Department of Pharmaceutical Chemistry, Netaji Subhas Chandra Bose Institute of Pharmacy, Roypara, Chakdaha Dist–Nadia, Pin‒741222, West Bengal, India. 2Department of Pharmaceutical Chemistry, School of Pharmacy, Techno India University, Salt‒Lake City, Sector‒V, EM‒4, Kolkata‒700091, West Bengal, India. 3Deputy Director of Technical Education, Directorate of Technical Education, Bikash Bhavan, Salt Lake City, Kolkata‒700091, West Bengal, India. *Corresponding Author: Arpan Chanda Department of Pharmaceutical Chemistry, Netaji Subhas Chandra Bose Institute of Pharmacy, Roypara, Chakdaha Dist–Nadia, Pin‒741222, West Bengal, India. Article Received on 05/07/2020 Article Revised on 26/07/2020 Article Accepted on 16/08/2020 ABSTRACT Insulin which is a peptide hormone is produced by β‒cells of the pancreatic islets and it is considered to be the main anabolic hormone of the body. It further regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose from the blood is thus converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver both glycogenesis and lipogenesis. Glucose production and secretion by the liver is strongly supported by high concentrations of insulin in the blood. Circulating insulin on the other hand also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone which promotes the conversion of small molecules in the circulating blood into large molecules inside the cells. Conversely low insulin levels in the blood have the opposite effect that promotes widespread catabolism, especially of reserve body fat. β‒cells of the pancreatic islets are specifically sensitive to blood sugar levels thus they secrete insulin into the circulating blood in response to high level of glucose; and conversely inhibits the secretion of insulin when blood glucose levels are low. Insulin is responsible for glucose uptake and metabolism in the cells, therefore reducing the blood sugar level. The α‒ cells which are present near the β‒cells of the pancreatic islets, takes their cues from the β‒cells and secretes glucagon into the blood in just the opposite manner i.e. increased glucagon secretion when blood glucose is low, and decreased glucagon secretion when glucose concentrations are high. Glucagon thus increases blood glucose level by stimulating glycogenolysis and gluconeogenesis in the liver. The secretion of insulin and glucagon into the circulating blood in respective response to the glucose concentrations in the blood is termed as glucose homeostasis. Insulin was the first peptide hormone discovered. Frederick Banting and Charles Herbert Best, working in the laboratory of J.J.R. Macleod at the University of Toronto, were the first to isolate insulin from dog pancreas in 1921. Frederick Sanger sequenced the amino acid structure in 1951, which made insulin the first protein to be fully sequenced. The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin in 1969. Insulin is also the first protein to be chemically synthesized and produced by DNA recombinant technology. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. KEYWORDS: α-cells, β-cells, Islets of Langerhans, Insulin, Glucagon, Polypeptide, Disulfide bonds, Lente Insulin, Semi Lente Insulin, Glucogenesis, Glycogenesis, Type-1 diabetes, Type-2 diabetes. INTRODUCTION These two are the basis of administration of two different types of commercially available insulins. The main Physiological insulin consists of two constituents they objective of insulin therapy in diabetes is to accomplish are: permanent blood glucose management by simulating 1. Basal (a relatively constant background level of normal insulin secretion from the pancreas. insulin during the fasting and post absorptive period) and Long‒acting insulins supply basal insulin, on the other 2. Bolus (prandial spikes of insulin after eating) hand short‒acting ones provide postprandial requirements. Elevation of postprandial blood glucose www.wjpmr.com 102 Arpan et al. World Journal of Pharmaceutical and Medical Research level results to notably elevation of glycated hemoglobin measured in milligrams per deciliter (mg/dL). Normal (HbA1C) values and resulting long term complications results for the two‒hour postprandial test based on age of diabetes. Therefore, postprandial regulation of blood are: For those who do not have diabetes: less than 140 glucose is indispensable for optimum diabetes disease mg/dL. For those who have diabetes: less than 180 management. Test results vary by age and are usually mg/dL.[1] Figure‒1: Frederick Sanger (Nobel Laureate), Frederick Banting (Nobel Laureate) and Charles Best (Medical Scientist); the scientists in Insulin discovery. In 1921, insulin was first given to a diabetic dog, and crystalline insulin. Insulin preparations consist of the thus was paving the way for human insulin therapy. All amino acid sequence of human insulin or variations insulin preparations are currently generated by thereof (insulin analogues). Eli Lilly and Sanofi used a recombinant DNA technology. Doses and concentration non‒pathogenic strain of Escherichia coli to synthesize levels of insulin preparations used in clinics are indicated insulin; whereas Novo Nordisk uses Saccharomyces by international units. Indeed, one international unit of cerevisiae, or bakers’ yeast.[2] insulin is defined as the bioequivalent of 34.7μg of Figure‒2: Insulin I.P. Official Preparation: The human insulin protein is clear solutions at neutral pH and have minor amounts of made up of 51 amino acids, with a molecular mass of zinc (for greater stability and shelf life). The insulin 5808 Da. It is a heterodimer of two chains i.e. an molecules usually exist as dimers which joins together to A‒chain and a B‒chain, which are linked together by form hexamers. Thus, when two zinc ions are present in disulfide bonds. Insulin's structure varies slightly the formulation and the formed hexamers further between different species of animals. Insulin from typically exhibit elevated stability in the presence of animal sources differs somewhat in effectiveness (in phenolic compounds such as phenol and meta‒cresol. carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially Pharmacokinetic properties of different types of somewhat close to the human version, and was widely short‒acting insulins are summarized in Table‒1. used to treat type‒1 diabetic before human insulin could Various clinical studies have indicated that the right time be produced in large quantities by recombinant DNA for pre‒prandial administration of regular human insulin technologies. and rapid‒acting insulin are 45 and 15 min before food, respectively. In general, the quick onset of action is Short‒acting Insulin Preparations: The regular human considered ideal as the patient can begin his food insulin and the rapidly acting insulin analogues are immediately after administering the dose.[3] For healthy considered as short‒acting formulations. Usually they are adults, normal pre‒prandial glucose levels are 70‒99 www.wjpmr.com 103 Arpan et al. World Journal of Pharmaceutical and Medical Research mg/dl. A pre‒prandial glucose reading of 100‒125 mg/dl The storage condition of the short‒acting insulin indicates prediabetes. preparations are given in Table‒2. Figure‒3: Slow and Rapid action of Insulin. Long‒acting Insulin Preparation NPH: NPH is an shaking of the insulin should be avoided because this equivalent mixture of protamine with native insulin in results in formation of foam, which disrupts the accurate water for injection adjusted to pH 7.1‒7.4 with measurement of the dose. To prevent clogging at the tip phosphate buffer. It is an opaque suspension consisting of the needle, NPH should be injected rapidly (<5sec) of rod‒shaped insulin crystals with particle size <30µm. subcutaneous.[4] Thawing refrigerated insulin to room The preparation should be free of large aggregates temperature prior to use will decrease irritation at the followed by moderate shaking for consistent absorption. injection site. The storage condition of the long‒acting The expiry date of the formulation should not be more insulin preparations are given in Table‒2. than 24‒36months from the date of manufacturing. In general, the absorption of NPH insulin is quick from Unopened vials of suspensions and prefilled syringes abdominal fat, relatively slow from posterior upper arms should be refrigerated between 2‒8°C and should not be and lateral thigh area, and slowest from superior buttocks subjected to freezing (<2°C) or exposed to heat (>30°C) area. Patients should be cautious for initial signs of or sunlight. Pharmacokinetic properties of long‒acting frosting or clumping of this insulin, as it shows a insulins are summarized in Table‒1. Pharmacokinetic noticeable loss of potency. This form of insulin must not properties of different insulin preparations are be administered through intravenous route. Since the summarized in the following Table. There is great active ingredient of this insulin is in the precipitate state, variability in the time of onset of action, peak effect, and vial should be gently agitated and mixed thoroughly to duration of action of insulin amongst individuals and assure a uniform mixture for accurate measurement of even with repeated doses in the same individual each dose. This is usually done by slowly swirling or depending on the dose size, the injection site, the carefully shaking or inverting the vial several times exercise, the desire of circulating anti‒insulin before withdrawal of each insulin dose.
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