Brockmann body

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Brockmann bodies isolated from an Atlantic wolffish. (A) Pancreatic tissues are scattered in the mesentery (black arrows). (B) The Brockmann body is indicated with an arrow. Brochmann body.jpg
Brockmann bodies isolated from an Atlantic wolffish. (A) Pancreatic tissues are scattered in the mesentery (black arrows). (B) The Brockmann body is indicated with an arrow.

Brockmann body is an endocrine organ in some teleost fish, and is composed of a collection of islet tissues. The islet tissues are in turn composed of endocrine cells which are the principal sites of insulin synthesis. [1] They are distributed around the spleen and the large intestine. They also secrete other hormones such as glucagon and somatostatin. Hence, Brochmann body is the centre of control of blood glucose level in these fishes. Glucagon is also produced from the intestine, but Brockmann body is the major source. Increased level of glucose stimulate the Brockmann body to release insulin, while inhibiting glucagon. Somatostatin released from Brockmann body inhibits cells to produce insulin and glucagon. In addition it inhibits release of growth hormone from the pituitary. [2] It is named after a German physician Heinrich Brochmann who discovered it in 1848. [3]

Contents

Brochmann body has gained a new attention in medical research, specifically in the management of type I diabetes mellitus. This is because the tissue is easy to harvest, and its insulin can be easily extracted. In addition, the teleost fishes can regenerate their endocrine tissues after harvest, the property of which has challenging implication in human diabetes. [4]

Structure

A typical Brochmann body is mass of whitish nodules of variable sizes, ranging from 1 to 8 mm in diameter. The nodules are composed of polygonal and elongated cells. The cells are enveloped with connective tissues. [5] They are separated into two major islets: one is found near the spleen and the other is located inside the wall of the duodenum, at the pyloric junction. [6] Both islet groups contain insulin, glucagon, peptide YY and somatostatin, but these proteins are secreted only in the pyloric Brockmann bodies. The amino acid sequence and primary structure of the hormones are slightly different from their counterparts in higher vertebrates. [7] [8] For example, tilapia and human insulin differs by 17 amino acids. [9] There are also amino acid variation among different species; for example, glutamine residue, at position 5 in the A-chain of insulin in most teleosts, is replaced by glutamic acid in tilapia. [10]

Medical significance

Brochmann body shows medical benefits in the management of endocrine and immunological disorders. An advantage of using teleost fish over other animals, such as pigs, in the studies of diabetes mellitus is that its endocrine cells are separated from the pancreatic exocrine tissue and can be easily isolated and harvested. While mammalian pancreas is expensive and laborious to collect. Further, fish tissue can be preserved in better condition for longer period. [9] Moreover, the teleost fishes can regenerate their endocrine tissues after harvest, implying that the property could be beneficial in type I diabetes mellitus. [4] The Brockmann body of the tilapia (Oreochromis nilotica) is investigated as a potential xenograft tissue for patients with type 1 diabetes. [10] The transplantation of tilapia Brockmann bodies into a diabetic mice model has been shown to promote long-term normal blood glucose level. [11] The tilapia islet grafts give better blood glucose level than rat or mouse islet grafts. [12] But as in mammalian transplant, tissue rejection is a problem. An attempt to solve this is creation of a transgenic tilapia that contain a human insulin gene. [13] These transgenic tilapia produce stable amount of human insulin, and are now undergoing selective breeding. [14]

Related Research Articles

Endocrine system The bodys hormone-producing glands

The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. In humans, the major endocrine glands are the thyroid gland and the adrenal glands. The study of the endocrine system and its disorders is known as endocrinology.

Insulin Peptide hormone

Insulin is a peptide hormone produced by beta cells of the pancreatic islets; it is considered to be the main anabolic hormone of the body. It 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 is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat.

Pancreas Organ of the digestive system and endocrine system of vertebrates

The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins, and fats in food entering the duodenum from the stomach.

Pancreatic islets

The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose.

Glucagon Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.

Glucagonoma is a very rare tumor of the pancreatic alpha cells that results in the overproduction of the hormone, glucagon. Typically associated with a rash called necrolytic migratory erythema, weight loss, and mild diabetes mellitus, most people with glucagonoma contract it spontaneously. However, about 10% of cases are associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome.

Endocrine gland Glands of the endocrine system that secrete hormones to blood

Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.

Incretin Group of gastrointestinal hormones

Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism.

Type 1 diabetes Form of diabetes mellitus

Type 1 diabetes (T1D), previously known as juvenile diabetes, is an autoimmune disease that originates when very little or no insulin is produced by the islets of Langerhans in the pancreas. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate normal glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks.

Pancreatic polypeptide Protein produced by the endocrine pancreas

Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine pancreas. It regulates pancreatic secretion activities, and also impact liver glycogen storage and gastrointestinal secretion. Its secretion may be impacted by certain endocrine tumours.

Glucagon-like peptide-1 Gastrointestinal Peptide Hormone Involved in Glucose Homeostasis

Glucagon-like peptide-1 (GLP-1) is a 30 or 31 amino acid long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 composes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.

Somatostatinomas are a tumor of the delta cells of the endocrine pancreas that produces somatostatin. Increased levels of somatostatin inhibit pancreatic hormones and gastrointestinal hormones. Thus, somatostatinomas are associated with mild diabetes mellitus, steatorrhoea and gallstones, and achlorhydria. Somatostatinomas are commonly found in the head of pancreas. Only ten percent of somatostatinomas are functional tumours [9], and 60-70% of tumours are malignant. Nearly two-thirds of patients with malignant somatostatinomas will present with metastatic disease.

Islet cell transplantation

Islet transplantation is the transplantation of isolated islets from a donor pancreas into another person. It is an experimental treatment for type 1 diabetes mellitus. Once transplanted, the islets begin to produce insulin, actively regulating the level of glucose in the blood.

Enteroendocrine cell

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota plays key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

Blood sugar regulation hormones regulating blood sugar levels

Blood sugar regulation is the process by which the levels of blood sugar, primarily glucose, are maintained by the body within a narrow range. This tight regulation is referred to as glucose homeostasis. Insulin, which lowers blood sugar, and glucagon, which raises it, are the most well known of the hormones involved, but more recent discoveries of other glucoregulatory hormones have expanded the understanding of this process.The gland called pancreas secrete two hormones and they are primarily responsible to regulate glucose levels in blood.

PDX1 A protein involved in the pancreas and duodenum differentiation

PDX1, also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster. In vertebrates, Pdx1 is necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1. The gene was originally identified in the clawed frog Xenopus laevis and is present widely across the evolutionary diversity of bilaterian animals, although it has been lost in evolution in arthropods and nematodes. Despite the gene name being Pdx1, there is no Pdx2 gene in most animals; single-copy Pdx1 orthologs have been identified in all mammals. Coelacanth and cartilaginous fish are, so far, the only vertebrates shown to have two Pdx genes, Pdx1 and Pdx2.

Insulitis Medical condition

Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas that helps regulate glucose levels, and is classified by specific targeting of immune cell infiltration in the islets of Langerhans. This immune cell infiltration can result in the destruction of insulin-producing beta cells of the islets, which plays a major role in the pathogenesis, the disease development, of type 1 and type 2 diabetes. Insulitis is present in 19% of individuals with type 1 diabetes and 28% of individuals with type 2 diabetes. It is know that genetic and environmental factors contribute to insulitis initiation, however, the exact process that causes it is unknown. Insulitis is often studied using the non-obese diabetic (NOD) mouse model of type 1 diabetes. The chemokine family of proteins may play a key role in promoting leukocytic infiltration into the pancreas prior to pancreatic beta-cell destruction.

Neurogenin-3

Neurogenin-3 (NGN3) is a protein that in humans is encoded by the Neurog3 gene.

The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.

Pancreatic progenitor cell

Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas.

References

  1. ↑ Pisharath, Harshan (2009). Characterizing Endocrine Progenitors in Developing and Regenerating Zebrafish Pancreas. p. 7. ISBN   978-1-10-913251-9.
  2. ↑ Ostrander, Gary K. (2000). The Laboratory Fish. San Diego: Academic Press. ISBN   978-0-12-529650-2.
  3. ↑ Suehiro, M (1992). "Historical review of insulin and its preparations in pharmacopoeia (3). Fish insulins". Yakushigaku Zasshi (in Japanese). 27 (1): 32–39. PMID   11639701.
  4. 1 2 Intine, Robert V.; Olsen, Ansgar S.; Sarras, Michael P. (2013). "A zebrafish model of diabetes mellitus and metabolic memory". Journal of Visualized Experiments. 72 (72): e50232. doi:10.3791/50232. PMC   3622110 . PMID   23485929.
  5. ↑ Fortin, Jessica S; Santamaria-Bouvier, Ariane; Lair, Stéphane; Dallaire, André D; Benoit-Biancamano, Marie-Odile (2015). "Anatomic and molecular characterization of the endocrine pancreas of a teleostean fish: Atlantic wolffish (Anarhichas lupus)". Zoological Studies. 54 (1): 21. doi: 10.1186/s40555-014-0093-4 . PMC   6661513 . PMID   31966108.
  6. ↑ Cutfield, JF; Cutfield, SM; Carne, A; Emdin, SO; Falkmer, S (1986). "The isolation, purification and amino-acid sequence of insulin from the teleost fish Cottus scorpius (daddy sculpin)". European Journal of Biochemistry. 158 (1): 117–23. doi: 10.1111/j.1432-1033.1986.tb09728.x . PMID   3525155.
  7. ↑ Conlon, JM; Schmidt, WE; Gallwitz, B; Falkmer, S; Thim, L (1986). "Characterization of an amidated form of pancreatic polypeptide from the daddy sculpin (Cottus scorpius)". Regulatory Peptides. 16 (3–4): 261–268. doi:10.1016/0167-0115(86)90025-x. PMID   3562898. S2CID   37619112.
  8. ↑ Conlon, JM; Davis, MS; Falkmer, S; Thim, L (1987). "Structural characterization of peptides derived from prosomatostatins I and II isolated from the pancreatic islets of two species of teleostean fish: the daddy sculpin and the flounder". European Journal of Biochemistry. 168 (3): 647–652. doi:10.1111/j.1432-1033.1987.tb13465.x. PMID   2889597.
  9. 1 2 Wright JR, Jr; Pohajdak, B (2001). "Cell therapy for diabetes using piscine islet tissue". Cell Transplantation. 10 (2): 125–143. doi: 10.3727/000000001783986864 . PMID   11332627.
  10. 1 2 Nguyen, TM; Wright JR, Jr; Nielsen, PF; Conlon, JM (1995). "Characterization of the pancreatic hormones from the Brockmann body of the tilapia: implications for islet xenograft studies". Comparative Biochemistry and Physiology C. 111 (1): 33–44. doi:10.1016/0742-8413(95)00023-z. PMID   7656183.
  11. ↑ Wright, J. R.; Polvi, S.; Maclean, H. (1992). "Experimental transplantation with principal islets of teleost fish (Brockmann bodies). Long-term function of tilapia islet tissue in diabetic nude mice". Diabetes. 41 (12): 1528–1532. doi:10.2337/diab.41.12.1528. PMID   1446792. S2CID   36311903.
  12. ↑ Yang, Hua; Dickson, Brendan C.; O'Hali, Wael; Kearns, Heather; Wright, James R. (1997). "Functional comparison of mouse, rat, and fish islet grafts transplanted into diabetic nude mice". General and Comparative Endocrinology. 106 (3): 384–388. doi:10.1006/gcen.1997.6878. PMID   9204372.
  13. ↑ Wright, J. R.; Pohajdak, B.; Xu, B.-Y.; Leventhal, J. R. (2004). "Piscine islet xenotransplantation". ILAR Journal. 45 (3): 314–323. doi: 10.1093/ilar.45.3.314 . PMID   15229378.
  14. ↑ Wright, James R.; Yang, Hua; Hyrtsenko, Olga; Xu, Bao-You; Yu, Weiming; Pohajdak, Bill (2014). "A review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a "humanized" tilapia insulin". Xenotransplantation. 21 (6): 485–495. doi:10.1111/xen.12115. PMC   4283710 . PMID   25040337.
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