Adiponectin

Leptin

PYY

Appetite

Glucose

GlucagonGhrelin

GIP

RBP

Glucose

ProinsulinC-Peptide

Insulin

Islet

Metabolite Immuno Assays

BioCat GmbHTechnologiepark Tel.: +49 (0) 6221 71415 16 Im Neuenheimer Feld 584 Fax: +49 (0) 6221 71415 29D-69120 Heidelberg E-Mail: info@biocat.com www.biocat.com

Diabetes and ObesityEnergy homeostasis is a well-regulated process that de-pends on the coordination between feeding behavior and energy expenditure. The control of energy homeosta-sis has received much attention in recent years due to al-terations caused by the onset of conditions such as diabe-tes and obesity. It is now recognized that there are many central and peripheral factors involved in energy homeo-stasis. Understanding of these mechanisms should lead to effective treatments for the control of diabetes, obesity and other metabolic disorders.Here we offer numerous assay kits to assist both academic and industry researchers with quantification of analytes associated with energy homeostasis and related diseases like type 2 diabetes mellitus, obesity, diabetic nephropa-thy, acute kidney injury or cardiovascular diseases.

www.biocat.com/diabetes

Autumn Special10% OFF selected metabolite ELISAs.Offer valid until 14 December 2012.For details see back of this brochure.

10% OFF*

Energy Homeostasis OverviewSystemic energy homeostasis is controlled by a complex net-work of tissues and secreted factors. Here we present a brief overview of the main organs and tissues involved.

Adipose TissueAdipose plays a much more active role in homeostasis than once thought. It has be found to be a source of lipid storage and mobilization, consists of specialized tissue able to produ-ce heat (brown adipose), and has the intrinsic ability to produ-ce and secrete an extensive number of factors. These so called adipocytokines consist of polypeptides and also nonprotein factors. They span different functional categories including immunity (complement factors, haptoglobin), endocrine function (leptin, sex steroids, various growth factors), meta-bolic function (fatty acids, adiponectin, resistin), and cardio-vascular function (angiotensinogen, PAI-1).

The BrainAs put elegantly by Dr. Barry Levin, the brain maintains a con-stant dialog with the external environment through inputs from somatic sensation, taste, smell, sight, and sound and the body by inputs from the viscera. These signals are relayed to a variety of brain areas through hard-wired neural connections and are complemented by metabolic and hormonal inputs that reflect the metabolic status of the body. These metabolic sensing neurons are clustered in sites scattered throughout the brainstem and forebrain and are integrated into a distri-buted network that links them to afferent and efferent pa-thways involved in the control of energy homeostasis. These signals can be augmented and influenced by adipocytokines (e.g. leptin) and factors released from the gut and stomach.

The IntestineThe effects of gut-derived hormones on metabolic function and energy homeostasis have been well characterized and published. One relevant factor to be mentioned is glucagon-like peptide-1 (GLP-1). It is secreted by epithelial intestinal L-cells in response to glucose and lipids and has been shown to enhance glucose-stimulated insulin secretion. In addition to its involvement with glucose homeostasis, GLP-1 reduces body weight and food intake, and slows gastric emptying. GLP-1 acts through a G protein-coupled receptor that is wide-ly distributed in the body including adipose tissue, stomach, brain, and others. PYY, a peptide also produced within the small intestine and rectum by L-cells has been shown to in-hibit gut motility and is proposed to stimulate a significant central satiety response.

The StomachThe anatomical neighbor of the intestines, the stomach, is re-sponsible for producing Ghrelin, the only known circulating orexigenic hormone. It is acylated with a medium-chain fatty acid by the enzyme ghrelin O-acetyltransferase (GOAT) and displays an extensive range of activity, from central control of

food intake to peripheral functions such as gastric emptying and insulin secretion.

The PancreasThe pancreas may have the most obvious involvement in en-ergy homeostasis. The pancreas is responsible for secretion of insulin and glucagon, two counteregulatory hormones that control systemic concentration of glucose used by cells as the primary source of energy. The pancreas releases insulin and glucagon directly based on concentration of glucose in the blood. Not only is insulin secretion regulated in this direct fashion, it is also controlled by the previously mentioned in-cretins (GIP and GLP-1), a group of gastrointestinal hormones that cause an increase in the amount of insulin released from beta cells after eating, even before blood glucose levels be-come elevated.

The LiverPancreatic function is tightly coordinated with function of the liver as it is responsible for releasing glucagon when blood sugar (glucose) levels fall too low. Glucagon, the counterpart of insulin, causes the liver to convert stored glycogen into glu-cose, causing release into the bloodstream.

Analyte Human Mouse Rat

Adiponectin (Multimeric)

Adiponectin (Total)

C-Peptide

GLP-1 (Glucagon-like Peptide 1, 7-36, 9-36)

GLP-1 (Glucagon-like Peptide 1, Active 7-36)

GLP-2 (Glucagon-like Peptide 2)

Glucagon

Growth Hormone

Growth Hormone (Ultrasensitive)

IL-6

IL-6 Ultrasensitive

Insulin

Insulin High Range

Insulin (Ultrasensitive)

Leptin

L-FABP (Liver Fatty Acid Binding Protein)

MCP-1 (Monocyte Chemotactic Protein 1)

Ghrelin

PYY (Peptide YY)

Proinsulin

Resistin

TNF-a

VEGF (Vascular Endothelial Growth Factor)

Overview of ELISA Assays for biomarkers in energy homeostasis.

= Autumn Special: 10% OFF. For the full list please see the back cover of this bro-

chure. For a full listing of all metabolite ELISAs at BioCat please use the ELISA search

engine on our website.

www.biocat.com/elisa

Diabetes and ObesityImmunoassays for Type 2 Diabetes and Obesity MarkersImpaired glucose tolerance observed in pre-type 2 diabetics is compensated for by increased secretion of insulin by pan-creatic β-cells. As type 2 diabetes progresses, however, the ability of pancreatic β-cells to secrete sufficient levels of in-sulin to stimulate glucose uptake by the insulin resistant pe-ripheral tissue diminishes due to decreased pancreatic β-cell mass/function, and, as a result, blood glucose levels rise.

Insulin ResistanceInsulin Resistance

Insulin

Type 2 DiabetesMellitus

β-cell dysfunction

Changes in insulin secretion associated with b-cell dysfunction.

Obesity is a medical condition in which body fat accumulates to the extent that alterations at the cellular level can increase the likelihood of various diseases, particularly heart disease, type 2 diabetes, obstructive sleep apnea, certain types of can-cer and osteoarthritis.

Macrophagerecruitment

Adipocyte

LeanNormal Adipose

• Small mature adipocyte• Macrophage• Adiponectin• TNFα, IL-6• Insulin sensitive

Central ObesityAdipose Dysfunction

• Inflamed heterogenous adipocytes• Macrophage accumulation• Adiponectin• TNFα, IL-6• Insulin resistant

Hallmarks of adipose dysfunction.

Please visit our website for a vast number of immunoassays for biomarkers involved in diabetes and obesity.

www.biocat.com/diabetes

Diabetes and Fracture RiskSclerostin - A Modulator of the Wnt PathwayAs the population continues to age, the prevalence of Diabe-tes Mellitus and Osteoporosis is increasing. Because Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of fractures, the relationship between the two diseases is cur-

rently under investigation. The wnt signaling pathway has recently been reported to be implicated: Too little activation can lead to reduced bone mass and too much activation can lead to excess bone mass. More recently, the wnt pathway has been reported to play a role in diabetes by impacting pancre-atic beta cell function through modulation of insulin secreti-on and regulation of cell viability.An inhibitor of the wnt signaling pathway, sclerostin, is re-leased from mature osteocytes and has been reported to be involved in bone diseases, rheumatoid arthritis, multiple my-eloma and bone metastases. More recently, circulating levels of sclerostin have been shown to be increased in the context of T2DM. While the pathogenesis of poor bone quality and in-creased fracture risk in the presence of diabetes remains to be clarified, the presence of elevated sclerostin levels may serve as a springboard for future research endeavors in this field.

www.biocat.com/sclerostin

Renal Tissue Injury and FunctionBiomarkers for Diabetic NephropathyDiabetic nephropathy (DN) is a major long term complication of diabetes mellitus. It is characterized by nephrotic syndrome and diffuse glomerulosclerosis due to longstanding diabetes mellitus1. Several new sensitive & site specific biomarkers may be used to recognize DN earlier than traditional methods.

Distal Markers • NGAL • KIM-1 • Clusterin

Glomerular Markers • Albumin • 6-2 Microglobulin • Cystatin C

Proximal Markers • KIM-1 • Clusterin • NGAL • 6-2 Microglobulin • Cystatin C • L-FABP • RBP • Alpha-GST

Biomarkers for Acute Kidney InjuryAcute kidney injury (AKI), also known as acute renal failure, is a prevalent and serious condition which is characterized by a rapid reduction in kidney function resulting in changes in flu-id balance and cellular homoeostasis. New injury site specific biomarkers have emerged to identify AKI at an earlier stage which could allow for faster treatment. They are being evalu-ated in various research, pre-clinical and clinical applications.

www.biocat.com/aki

BioCat GmbHTechnologiepark Tel.: +49 (0) 6221 71415 16 Im Neuenheimer Feld 584 Fax: +49 (0) 6221 71415 29D-69120 Heidelberg E-Mail: info@biocat.com www.biocat.com

Cardiovascular DiseaseBiomarkers of Heart Disease and Oxidative StressCardiovascular diseases (CVDs) have been shown to be tightly linked to obesity and type 2 diabetes. CVD is comprised of se-veral different diseases that affect the heart itself and/or the circulatory system. Some examples include: coronary artery disease, cardiomyopathy, ischemic heart disease and heart failure. Despite advances in medical technology and thera-peutics, CVD remains the leading cause of death worldwide.

Brain • Cortisol • Aldosterone

Other • Cystatin C • Bradykinin • Fibrinogen • PAI-1

Kidneys • Renin

Liver • Hemopexin • Ferritin • C-reactive Protein • Apolipoprotein A1

Heart & Muscle Cells • Myoglobin

In an effort to provide a more detailed picture of the risk of cardiovascular disease, researchers have been searching for novel biomarkers of CVD. Some biomarkers which have shown to be reflective of a higher risk of cardiovascular di-sease include fibrinogen, PAI-1 and C-reactive protein. As more biomarkers of CVD are better understood, they have the potential of becoming therapeutic targets.

www.biocat.com/cardiovascular

Autumn SpecialSpecial Offer for Selected ELISA AssaysUntil 14 December we offer 10% off the list price for the fol-lowing ELISA Kits for the sensitive detection of biomarkers and analytes involved in energy homeostasis and renal tissue function. When placing an order please refer to promotional code BIOCADO2012.

Product Cat#

Insulin Ultrasensitive ELISA Mouse 80-INSMSU-E01-AL

Insulin Ultrasensitive ELISA Mouse (Jumbo) 80-INSMSU-E10-AL

Insulin Ultrasensitive ELISA Rat 80-INSRTU-E01-AL

Insulin Ultrasensitive ELISA Rat (Jumbo) 80-INSRTU-E10-AL

Insulin ELISA Human 80-INSHU-E01.1-AL

Insulin ELISA Human (Jumbo) 80-INSHU-E10.1-AL

C-Peptide ELISA Mouse 80-CPTMS-E01-AL

C-Peptide ELISA Rat 80-CPTRT-E01-AL

C-Peptide ELISA Human 80-CPTHU-E01.1-AL

C-Peptide ELISA Human (Jumbo) 80-CPTHU-E10-AL

Proinsulin ELISA Mouse 80-PINMS-E01-AL

Proinsulin ELISA Rat 80-PINRT-E01-AL

Proinsulin ELISA Human 80-PINHU-E01.1-AL

Sclerostin ELISA Mouse 41-SCLMS-E01-AL

Product Cat#

Alpha GST ELISA Rat 80-AGTRT-E01-AL

Clusterin ELISA Rat 41-CLURT-E01-AL

Cystatin C ELISA Human 41-CYCHU-E01-AL

Cystatin C ELISA Rat 41-CYCRT-E01-AL

KIM-1 ELISA Rat 41-KIMRT-E01-AL

L-FABP (Liver Fatty Acid Binding Protein) ELISA Human 41-LFAHU-E01-AL

L-FABP (Liver Fatty Acid Binding Protein) ELISA Rat 41-LFART-E01-AL

*This special offer is valid until 14 December 2012

www.biocat.com/elisa

10% OFF*