Diabetes Products, Brochure Interest in any of the products, request or order them at Bio-Connect Diagnostics. Bio-Connect Diagnostics B.V. T NL +31 (0)26 326 44 60 T BE +32 (0)2 502 12 53 Begonialaan 3a F NL +31 (0)26 326 44 61 F BE +32 (0)2 502 12 77 6851 TE Huissen E info@bio-connectdiagnostics.nl The Netherlands W www.bio-connectdiagnostics.nl
MERCODIA DIABETES PRODUCTS Assays for Glucagon, Insulin, C-peptide and Proinsulin WHEN ACCURACY MATTERS www.mercodia.com
MERCODIA DIABETES PRODUCTS Human Assays CATALOG NO 10-1136-01 10-1141-01 10-1273-01 10-1271-01 10-1113-01/10 10-1132-01 10-1128-01 10-1118-01 PRODUCT NAME Mercodia C-peptide Mercodia Ultrasensitive C-peptide Mercodia Glicentin Mercodia Glucagon Mercodia Insulin /10 x 96 wells Mercodia Ultrasensitive Insulin Mercodia Iso-Insulin Mercodia Proinsulin Related Rat and Mouse Assays SAMPLE VOLUME 50 µl 50 µl RANGE - 4000 pmol/l 5-230 pmol/l 3-300 pmol/l 1.5-130 pmol/l 3-200 mu/l 0.15-20 mu/l 3 - mu/l 3.3-132 pmol/l CATALOG NO PRODUCT NAME SAMPLE VOLUME RANGE 10-1172-01 10-1275-01 10-1281-01 10-1247-01/10 10-1249-01 10-1250-01/10 10-1251-01 10-1248-10 10-1232-01 Mercodia Rat C-peptide Mercodia Rat Glicentin Mercodia Glucagon 10 µl Mercodia Mouse Insulin Mercodia Mouse Ultrasensitive Insulin Mercodia Rat Insulin /10 x 96 wells Mercodia Rat Ultrasensitive Insulin Mercodia Rat/Mouse Insulin FIA 10 x 96 wells Mercodia Rat/Mouse Proinsulin 10 µl 10 µl 10 µl 10 µl 1 2 10 µl 1 10 µl - 4000 pmol/l 5-500 pmol/l 2-180 pmol/l 0.2-6.5 µg/l 0.025-1.5 µg/l 0.15-5.5 µg/l 0.02-1 µg/l 0.15 - µg/l 3.5-200 pmol/l 1 5 µl application available, TN34-0130 2 10 µl application available, TN34-0132 Animal Products CATALOG NO PRODUCT NAME FORMAT RANGE 10-1256-01 10-1271-01 10-1281-01 10-1201-01 10-1203-01 10-1205-01 10-1233-01 10-1202-01 10-1200-01 2 Diabetes Products, Mercodia Mercodia Porcine C-peptide Mercodia Glucagon Mercodia Glucagon 10 µl Mercodia Bovine Insulin Mercodia Canine Insulin Mercodia Equine Insulin Mercodia Feline Insulin Mercodia Ovine Insulin Mercodia Porcine Insulin 20-1200 pmol/l 1.5-130 pmol/l 2-180 pmol/l 0.05-3.0 µg/l 2.3-173 mu/l 2.3-173 mu/l 10-700 ng/l 0.05-3.0 µg/l 2.3-173 mu/l
Supplements CATALOG NO. PRODUCT NAME VOLUME 10-1164-01 10-1134-01 10-1286-01 10-1220-01 10-1221-01 Mercodia Diabetes Antigen Control L and H Human Mercodia Diabetes Antigen Control Human L and H (unassayed) Mercodia Glucagon Control L, M, H Mercodia Diabetes Antigen Control Rat and Mouse L, M, H Mercodia Animal Insulin Control L, M, H 2 x 0.5 ml 2 x 0.5 ml 3 x 0.5 ml 3 x 0.5 ml 3 x 0.5 ml MERCODIA WHEN ACCURACY MATTERS Mercodia AB is a Swedish biotech company that develops and markets immunoassay kits within the fields of diabetes, obesity and cardiovascular disease. Our goal is to provide our customers with high quality assays with the following features: Monoclonal antibodies in all products ensures assays of high specificity. Reproducibility lot-to-lot consistency expected from using monoclonal antibodies. High precision low assay Coefficient of Variation (CV). Convenient and customer friendly color-coded reagents in a ready-to-use format. Breakable strip plates give the customer the option of using the whole or part of the plate. Time saving the format provides results fast (within 1.5-3.5 h). Support and service since all our products are developed and produced in-house, technical support is provided by the scientists that know the products best. All of the human diabetes products are CE-labeled. Since our researchers at Mercodia work in close collaboration with our research customers, the Mercodia assays well fulfill customer needs and requirements. Diabetes Products, Mercodia 3
Proinsulin molecule Diabetes Diabetes mellitus is a medical disorder characterized by elevated blood glucose levels (hyperglycemia). If blood glucose exceeds levels that the body is able to utilize, excess sugar is secreted in the urine. Increased amounts of urine are then produced and the patient becomes very thirsty. Untreated diabetes can lead to dehydration and ketoacidosis. Although the cause of diabetes may differ, all types of diabetes share the same symptoms and late stage complications, such as cardiovascular disease, renal failure, retinal damage with eventual blindness, nerve damage and tissue necrosis (diabetic foot). Diabetes mellitus type 1, or insulin dependent diabetes mellitus (IDDM), is mostly diagnosed in children and juveniles, but can debut in adults as well. It is an auto-immune disease in which the bodies own immune system attacks the insulin producing beta cells in the islets of Langerhans of the pancreas, which leads to a loss of insulin production. The cause of this is yet uncertain, but the autoimmune attack may be triggered by chemicals, nutrition or by a reaction to a virus infection. Pancreatic problems such as inflammation (pancreatitis) or tumors may also lead to loss of insulin production and IDDM. Type 1 diabetes is currently treated with insulin injections, careful monitoring of the blood glucose levels and lifestyle adjustments. 4 Diabetes Products, Mercodia Diabetes mellitus type 2, or non-insulin dependent diabetes mellitus (NIDDM), is most commonly diagnosed in middle-aged, often obese, individuals and is characterized by insulin resistance. This may be caused by a general reduction in insulin receptors, a decreased insulin affinity of the receptors or by post-receptor defects of the target cells (muscle cells, fat cells). Normally insulin is released from beta cells through a process in which the insulin precursor, proinsulin is enzymatically processed into insulin and C-peptide. To overcome the insulin resistance in NIDDM patients, insulin is overproduced from the pancreas, which eventually may lead to an exhaustion of the insulin production capacity (beta cell dysfunction). As a result of exhaustion of the proinsulin processing enzymes, unprocessed or partly processed proinsulin may be secreted in addition to insulin and C-peptide. It has been shown that proinsulin is an independent risk factor for cardiovascular disease in type 2 diabetic patients by the stimulation of PAI-1 secretion and consecutively a decreased fibrinolytic activity. Initially type 2 diabetes is treated with changes in the diet and weight loss and if necessary with oral anti-diabetic drugs. If this fails, insulin therapy may be necessary.
Diabetes research Mercodia diabetes assays are used within a variety of different areas of diabetes research including evaluation of islets for transplantation, studies of differentiation of cells into insulin producing cells, pharmacokinetics of insulin analogs, insulin resistance, hyperinsulinaemia, viral infection and its effects on islets and in the studies of rat and mouse models of beta cell impairment and hyperglyceamia. Lindström et al. (2002) combined the Insulin (detects human insulin only) with the Iso-Insulin (detects human insulin as well as the insulin analogs) in studies of insulin pharmacokinetics in type 1 diabetic patients. Craig et al. (2003) used the Ultrasensitive C-peptide in studies of the correlation of blood C-peptide levels and occurrence of enterovirus RNA in children with type 1 diabetes. They found that patients with high C-peptide levels were significantly more likely to be negative for enterovirus RNA. Pellmé et al. (2003) found an inverse correlation of proinsulin to adiponectin in first-degree relatives of type 2 diabetic patients by using the Proinsulin. The Rat Insulin s and Mouse Insulin s have been used in several in vivo studies of rat and mouse models as well as in in vitro studies of rat and mouse derived cell and tissue cultures. Blyszczuk et al. (2003) used the Mouse Insulin to monitor insulin secretion from embryonic stem cells differentiated into insulin producing cells. Transplantation of these cells into diabetic mice resulted in a normalization of blood glucose levels. Jaeckel et al. (2004) monitored insulin production in transgenic mice by measuring insulin levels in organ extracts with the Ultrasensitive Mouse Insulin. Burcelin and colleagues (2003) used the Ultrasensitive Mouse Insulin on plasma samples from transgenic mice in their studies of GLUT4, AMP kinase and the insulin receptor. Kullin et al. (2003) used the High Range Insulin to monitor insulin release from isolated rat pancreatic islets pretreated with the potassium channel openers diazoxide or NNC 55-0118 before exposure to the beta cell-suppressive substances alloxan, sodium nitroprusside or IL-1b. Buettner and colleagues (2006) studied rats and the impact of various diets with different fat constitution on insulin secretion and other plasma characteristics by using the Rat Insulin. Animal models and in vitro cell and tissue cultures from larger animals are widely used in diabetic research as well as in insulin monitoring within veterinary medicine. For example in islet transplantation, the shortage of human donors and difficulty in isolating purified islets from human pancreas has drawn attention to the possibility of xenotransplantation with porcine pancreatic islets. Furthermore, extensive research is conducted on insulin resistance, diabetes mellitus and how to improve the nutritional, metabolic and health status of ruminants, horses and companion animals. Matching energy intake with the energy expenditure is important for the exercising horse. Diabetes mellitus is one of the most common endocrine disorders in dogs. Mercodia provides species specific optimized assays for measurements of insulin in Porcine, Bovine, Ovine, Canine, and Equine samples, all valuable tools for your insulin measurement quality. Alignment of proinsulin sequences Rat 2 Mouse 2 Rat 1 Mouse 1 Hamster Guinea pig Rabbit Human Sheep Bovine Porcine Horse Dog CPH PC1 CPH PC2 20 40 60 80 Insulin B-chain C-peptide Insulin A-chain Accession No: NP_062003 (Rat2), NP_032413 (Mouse 2), NP_062002 (Rat 1), NP_032412 (Mouse 1), P01313 (Hamster), AAA37041 (Guinea pig), AAA19033 (Rabbit), NP_000198 (Human), AAB60625 (Sheep), NP_776351 (Bovine), AAC77920 (Porcine), P01310 (Horse), P01321 (Dog). CPH = carboxypeptide H, PC1 = prohormone convertase 1, PC2 = prohormone convertase 2. Diabetes Products, Mercodia 5
Specificity of human diabetes products ANTIGEN Insulin C-peptide Proinsulin Proinsulin des (31-32) Proinsulin split (32-33) Proinsulin des (64-65) 1 Proinsulin split (65-66) 1 Insulin lispro Insulin aspart Insulin detemir Insulin glargin Insulin glulisine IGF-I IGF-II Rat Insulin Mouse Insulin Porcine Insulin Ovine Insulin Bovine Insulin C-PEPTIDE < 0.0006 < 1.8 3 2 74 10 ULTRASENSITIVE C-PEPTIDE < 0.0006 < 1.8 3 2 74 10 INSULIN < 0.5 < 0.5 98 56 19 0.7 0.3 374 48 31 ULTRASENSITIVE INSULIN < 0.5 < 0.5 98 56 19 0.7 0.3 374 48 31 ISO-INSULIN < 0.1 54 58 56 66 78 89 80 22 44 71 49 306 131 58 1) Des (64-65) and split (65-66) proinsulin are reported to be least abundant of the proinsulin like molecules in circulation (< 1 pm to 5 pm). Sobey WJ et al. (1989) Biochem J 260:535-541, Kahn SE and Halban PA (1997) Diabetes 46:1725-1732. PROINSULIN < 0.03 < 0.006 95 95 84 Specificity of rat/mouse diabetes products ANTIGEN MOUSE INSULIN ULTRASENSITIVE MOUSE INSULIN RAT/MOUSE PROINSULIN ULTRASENSITIVE RAT INSULIN RAT INSULIN Human Insulin Human Proinsulin Human C-peptide Insulin lispro IGF-I IGF-II Rat C-peptide Rat Insulin Rat Proinsulin Mouse Insulin Mouse C-peptide Porcine Insulin Ovine Insulin Bovine Insulin 195 82 < 0.05 146 14 628 256 110 195 82 < 0.05 146 14 628 256 110 5 < 0.0003 167 75 < 0.05 167 7 75 476 179 78 167 75 < 0.05 167 7 75 476 179 78 Specificity of animal diabetes products ANTIGEN BOVINE INSULIN CANINE INSULIN EQUINE INSULIN FELINE INSULIN OVINE INSULIN PORCINE INSULIN Porcine Insulin Porcine C-peptide Porcine Proinsulin Human Insulin Human C-peptide Human Proinsulin Insulin aspart Insulin detemir Insulin lispro Insulin glargin Insulin lispro Insulin glulisine Caninsulin 3.8 28 < 0.2 108 < 0.1 5.4 < 3 < 0.2 108 < 0.1 5.4 5.9 < 0.008 8.4 57.4 2.0 21 < 0.2 108 < 0.1 5.4 = not detected 6 Diabetes Products, Mercodia All figures in %
References Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St-Onge L, Wobus AM: Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci USA :998-3, 2003 Buettner R, Parhofer K, Woenckhaus M, Wrede CE, Kunz- Schughart LA, Schšlmerich J, Bollheimer LC: Defining high fat diet rodent models: metabolic and molecular effects of different fat types. J Mol Endocrinol E-pub February 2006 Burcelin R, Crivelli V, Perrin C, Da Costa A, Mu J, Kahn BB, Birnmaum MJ, Kahn CR, Vollenweider P, Tjorens B: GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization. J Clin Invest 111:1555-1562, 2003 Craig ME, Howard NJ, Silink M, Rawlinson WD: Reduced frequency of HLADRB1*03-DQB1*02 in children with type 1 diabetes associated with enterovirus RNA. J Infect Dis 187:1562-1570, 2003 Jaeckel E, Lipes MA, von Boehmer H: Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes. Nat Immunol 5:1028-1035, 2004 Kullin M, Li Z, Bondo Hansen J, Welsh N, Karlsson FA, Sandler S: Protection of ratpancreatic islets by potassium channel openers against alloxan, sodium nitroprusside and interleukin-1beta mediated suppression-possible involvement of the mitochondrial membrane potential. Diabetologia 46:80-88, 2003 Lindstrom T, Hedman CA, Arnqvist HJ: Use of a novel doubleantibody technique to describe the pharmacokinetics of rapidacting insulin analogs. Diabetes Care 25: 1049-1054, 2002 Pellmé F, Smith U, Funahashi T, Matsuzawa Y, Brekke H, Wiklund O, Taskinen M-R, Jansson P-A; Circulating Adiponectin Levels Are Reduced in Nonobese but Insulin-Resistant First-Degree Relatives of Type 2 Diabetic Patients. Diabetes 52; 1182-1186, 2003 Diabetes Products, Mercodia 7
WHEN ACCURACY MATTERS www.mercodia.com Global Headquarters Mercodia AB Phone +46 18 57 00 70 Fax +46 18 57 00 80 E-mail info-europe@mercodia.com Sales Office USA Mercodia Inc Phone +1 (336) 725-8623 Fax +1 (336) 725-8673 E-mail info-usa@mercodia.com Sales Office France Mercodia France SAS Phone +33 6 13 38 4802 Fax +46 18 57 00 80 E-mail info-europe@mercodia.com Sales Office Germany Phone +49 211 163 568 79 Fax +46 18 57 00 80 E-mail info-europe@mercodia.com 2017-05-03 Version 4.0, Article no. 32-3202