Endocrinology/Hormones

<p>Vasopressin is a peptide antidiuretic hormone, originating from the hypothalamus, that regulates water balance in the body. It is also known as arginine vasopressin or antidiuretic hormone (ADH). The clinical efficacy of vasopressin has been evaluated using in vitro methods on mouse monoclonal antibody production cells, blood sampling, and microdialysis probes for monitoring blood pressure. This product is available in the salt form: Acetate.</p>

<p>The cleavage of proglucagon forms glucagon. Increased levels of glucagon that can't be regulated are linked to diabetic hyperglycaemia and other pathologies. Typically, glucagon levels should be suppressed as glucose levels rise. However, the opposite has generally been found to be accurate, and the nature of this elevated immunoreactive glucagon has led to more research. Hyperglucagonaemia is a characteristic of several pathologies, but the detection of immunoreactive glucagon has yet to be fully verified due to the nature of available detection.Glucagon can be hydrolysed by dipeptidyl peptidase IV (DPIV) to products such as (18-29) and (3-29). Current methods for detecting glucagon rely on antibodies to the N terminus or  C-terminus to detect pancreatic glucagon. However, these antibodies may also detect truncated forms due to a pathology affecting the secretion, clearance or processing of proglucagon-derived peptides. Theoretically, these can be used in a sandwich process to detect only full-length glucagon. Therefore, the availability of the truncated glucagon (3-29) as a control to test the sensitivity of the available antibodies and the ELISAs is useful. Plasma levels from hyperglucagonaemic patients and healthy counterparts were used as a control to test the commercial glucagon assays and ELISAs. The truncated glucagon (3-29) provided valuable information about the sensitivity and specificity of the antibodies that have been used as an industry standard for glucagon measurement. This truncated glucagon is vital in ensuring our research moves forward with more controls and fewer assumptions.</p>

<p>Peptide derived from the Gastric inhibitory polypeptide (GIP), an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide.GIP is derived from a 153-amino acid pro-protein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.</p>

<p>Gastric inhibitory polypeptide (GIP) is an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide.GIP is derived from a 153-amino acid pro-protein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.</p>

<p>N-terminal tryptic peptide of parathyroid hormone (PTH), used for quantification and optimisation in LC-MS/MS assays.PTH is an 84-amino-acid polypeptide hormone (PTH 1-84) which is secreted by the parathyroid glands along with its fragments (such as PTH 1-34 and PTH 7-84). PTH increases calcium and decrease phosphate levels in the blood and the abundance of PTH-derived peptides is regulated by blood calcium levels. PTH inhibits the bone growth-promoting activity of osteoblasts and induces osteoclasts to resorb bone and release calcium and phosphate ions into the blood. PTH binds to and activates the receptor parathyroid hormone receptor 1 (PTHR1). PTHR1 is a G-protein-coupled receptor (GPCR) which regulates mineral ion homeostasis, bone turnover and skeletal development</p>

<p>ANP (1-23) is derived from the atrial natriuretic peptide (ANP) which is a cardiac hormone involved in maintaining cardio-renal homeostasis. This occurs through the activation of the guanylyl cyclase-coupled receptor, resulting in the increased concentration of cyclic guanylate monophosphate. Moreover its function in the processes of anti-proliferation and anti-angiogenesis allow it to take part in cardiovascular remodelling.ANP is a member of the natriuretic peptide family and it is encoded by the NPPA gene, located on chromosome 1. Once synthesized from the 151 amino acid pre-prohormone into its biologically active form, ANP is secreted by the atrial cardiomyocytes in the circulating forms: ANP (1-98) and ANP (99-126). This synthesis process involves the signal peptide being removed from the pre-prohormone resulting in pro-ANP (1-126) which is converted into the circulating forms by the type II transmembrane serine protease Corin.</p>

<p>This is a truncated exendin-4 peptide, the original peptide was identified in Gila monster lizard (Heloderma suspectum). Exendin-4 is an incretin mimetic, an analog of glucagon-like-peptide-1 (GLP-1), it stimulates insulin secretion and modulates gastric emptying to slow the entry of ingested sugars into the bloodstream. Exendin-4 is resistant to cleavage by plasma DPP-IV unlike GLP-1. This gives it a longer half-life and duration of action than GLP-1, as well as greater potency in vivo. Exendin-4 increases insulin sensitivity and improves glucose tolerance and is currently used for the treatment of Type 2 diabetes mellitus in its synthetic form Exenatide.Exendin-4 also promotes the production and proliferation of β-cells leading to regeneration of the pancreas. It is a ligand to the exendin receptor and increases pancreatic acinar cell cAMP levels. However, the GLP-1 analog was found to have a toxic effect by inducing hypotension due to relaxation of the cardiac smooth muscle.</p>

<p>Calcitonin is a peptide hormone excreted by the thyroid parafollicular cells to regulate calcium and phosphorus levels. Calcitonin acts in opposition to parathyroid hormone (PTH) and vitamin D. Calcitonin functions by inhibiting osteoclast activity in the bones preventing calcium release- there is also inhibition of renal tubular cell reabsorption of calcium and phosphate, so they are excreted preventing a rise in levels.Calcitonin is used for as marker for detection and prognosis of nodular thyroid diseases. Medullary thyroid cancer is one example of the malignant parafollicular cells detectable with the assay, as they present with an increased calcitonin level even at an early stage.Since the discovery of calcitonin over 50 years ago the salmon sourced peptide has been used in numerous treatments including bone metastases, Paget disease, hypercalcaemia, and postmenopausal osteoporosis. The salmon calcitonin has been shown to be equivalent to human form but more active and can be synthetically generated.</p>

<p>Peptide derived from the gastrointestinal hormone Motilin, secreted from endocrine cells in the small intestines, mainly from the jejunum and duodenum, in response to the fasting, drinking water or the mechanical stimulus of eating.</p>

<p>This 32 amino acid peptide contains a 17 amino acid ring structure that is common to all natriuretic peptides. It is also called the brain natriuretic peptide (BNP) because it was first identified in porcine brain- however, the main source of this peptide is not the brain but the cardiac ventricle. This cardiac neurohormone is secreted from the ventricles in response to volume expansion and pressure overload. It has natriuretic and vasodilatory effects and suppresses the renin-angiotensin-aldosterone system.</p>

<p>PTH 1-34, is a biologically active peptide fragment of parathyroid hormone (PTH). PHT 1-34 has been shown to enhance bone fracture healing by promoting osteogenesis. PTH 1-34 also has chondrogenic properties.PTH is an 84-amino-acid polypeptide hormone (PTH 1-84) which is secreted by the parathyroid glands along with its fragments (such as PTH 1-34 and PTH 7-84). PTH increases calcium and decrease phosphate levels in the blood and the abundance of PTH-derived peptides is regulated by blood calcium levels. PTH inhibits the bone growth-promoting activity of osteoblasts and induces osteoclasts to resorb bone and release calcium and phosphate ions into the blood. PTH binds to and activates the receptor parathyroid hormone receptor 1 (PTHR1). PTHR1 is a G-protein-coupled receptor (GPCR) which regulates mineral ion homeostasis, bone turnover and skeletal development.</p>

<p>C- terminal fragment of adrenocorticotropic hormone (ACTH) also known as corticotropin, and competitive antagonist of ACTH receptor (ACTHR), also known as melanocortin type 2 receptor (MC2R).ACTH is a member of the melanocortins-peptide family, this tropic hormone is produced and secreted by the anterior pituitary gland. ACTH is an important component of the hypothalamic-pituitary-adrenal (HPA) axis and is often produced in response to biological stress. ACTH acts to increase the production and release of cortisol via its interaction with ACTHR. Receptor activation increases the intracellular concentration of cAMP via adenylyl cyclase. Abnormal ACTH levels in the body have been linked to primary adrenal insufficiency/Addison's disease, Cushing's disease and secondary adrenal insufficiency.</p>

<p>Mammalian bombesin-like peptide neurotransmitter that is an agonist for the gastrin-releasing peptide receptor (GRPR). It exhibits physiological functions such as gastrin and somatostatin release and chemoattraction within the immune system.</p>

<p>Pro B-type natriuretic peptide (Pro-BNP) is secreted from cardiac myocytes and cleaved into BNP and the remaining part of the prohormone N-terminal proBNP (NT-proBNP). When the heart fibres become stretched more BNP and NT-proBNP are released to try and compensate for the increased pressure. During heart failure the walls of the atria become over stretched and thus increase the levels of NT-proBNP detectable. NT-proBNP has a longer half-life than BNP and therefore is detectable at higher levels in blood plasma than BNP. NT-pro-BNP is believed to be cleared by renal excretion, but this is not confirmed. As a diagnostic tool, NT-proBNP (47-76) has become very useful in helping diagnose heart failure and provide a prognosis. The measurement of NT-proBNP (47-76) has been incorporated into management and guidelines of clinical settings. As a research tool it still provides valuable data such as symptoms onset in relation to NT-proBNP levels and how inflammation effects the level of BNP as well as the BNP/ NT-proBNP ratio.</p>

<p>Gastric inhibitory polypeptide (GIP) is an inhibiting hormone of the secretin family of hormones. While GIP is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion - in a glucose-dependent mechanism. Therefore, GIP is referred to as a glucose-dependent insulinotropic peptide. In GIP (Pro 3) the glutamic acid at position 3 has been substituted for a proline.GIP is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesised by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. GIP receptors are seven-transmembrane proteins found on β-cells in the pancreas. These β-cells are those that are able to simultaneously detect glucose and release insulin as a result to GIP binding.The clinical relevance of GIP is related to type 2 diabetes mellitus (T2DM)- studies have found that T2DM diabetics are unresponsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.</p>

<p>Insulin is a polypeptide composed of two peptide chains referred to as the alpha chain and β chain. These chains are linked by two disulphide bonds, and an additional disulphide is formed within the alpha chain. In most species, the alpha chain consists of 21 amino acids and the β chain of 30 amino acids. Insulin is normally secreted rapidly from the β-cells of the pancreatic islets in response to nutrients absorbed after a meal. In type 1 diabetes mellitus, there may be an absolute insulin deficiency as a consequence of autoimmune destruction of the β-cells. On the other hand, in type 2 diabetes mellitus, insulin secretion is impaired and is inadequate to overcome peripheral insulin resistance.</p>

<p>The heptapeptide Alexamorelin is a member of the Growth Hormone secretagogues (GHS) family. These are synthetic molecules which act through the central nervous system to stimulate the secretion of somatotrophs, prolactin, adrenocorticotrophin and cortisol. Alexamorelin has also been shown to inhibit 125I-Tyr-Ala-HEX binding in tissues. Due to their stimulation of growth hormone release, they are known as non-approved pharmaceuticals and are a concern to sport's drug testing organisations.</p>

<p>Residues 1-10 of the gastrointestinal hormone motilin, secreted from endocrine cells in the small intestines, mainly from the jejunum and duodenum, in response to the fasting, drinking water or the mechanical stimulus of eating.</p>

<p>The hormone Calcitonin, reduces the amount of serum calcium during hypercalcemia and is released from the C-cells of the thyroid gland. Within its structure it contains a disulphide bridge between cysteine 1 and 7 and a proline at its carboxy terminal.Calcitonin is used therapeutically in the treatment of hypercalcemia diseases such as Paget disease, Sudeck atrophy, bone metastases and vitamin-D intoxication.The level of calcitonin in the plasma can also be used as a marker for medullary thyroid carcinoma, while procalcitonin is used to diagnose sepsis.</p>

<p>Mammalian bombesin-like neuropeptide- first isolated from pig spinal cord, which can stimulate rat uterine smooth muscle contraction and gastrin and somatostatin secretion in vitro. Increases blood pressure and pancreatic exocrine secretion in dogs.</p>