Langerhans is the endocrine part of the pancreas, and it is a large number of cell clusters with different sizes and shapes, which are scattered all over the pancreas. Hormones produced by islets become insulin, which can control carbohydrate metabolism. If insulin secretion is insufficient, you will suffer from diabetes.

pancreatic islet

Islets can secrete hormones such as insulin and glucagon. Human islet cells are mainly divided into A cells and B normal islets according to their staining and morphological characteristics.

Cells, d cells and PP cells. A cells account for about 20% of islet cells and secrete glucagon. B cells account for 60%-70% of islet cells and secrete insulin; D cells account for 10% of islet cells and secrete somatostatin; PP cells are few in number and secrete pancreatic polypeptide.

Edit this insulin

Insulin is a small molecule protein containing 5/kloc-0 amino acids, with a molecular weight of 6000. Insulin molecules have a chain (265,438+0 amino acids) and a chain (30 amino acids) which are bound by two disulfide bonds. If the disulfide bond is opened, it will lose its activity. B cells first synthesize a large molecule of proinsulin, then process it into 86-peptide proinsulin, and then hydrolyze it into insulin and connecting peptide (C peptide). Insulin and C-peptide are released into the blood together, and a small amount of proinsulin enters the blood, but its biological activity is only 3%-5% of insulin, while C-peptide has no insulin activity. Because C-peptide is produced in the process of insulin synthesis, its quantity has a parallel relationship with insulin secretion, so measuring the content of C-peptide in blood can reflect the secretory function of B cells. The serum insulin concentration of normal people in fasting state is 35- 1.45 pmol/L, and the half-life of insulin in blood is only 5 minutes, which is mainly inactivated in the liver, and muscles and kidneys can also inactivate insulin. 1965, China biochemists synthesized insulin with high biological activity for the first time, which became the first pioneering work to synthesize living organisms (protein) in human history.

Edit the biological function of insulin in this paragraph.

Insulin is the main hormone to promote anabolism and regulate blood sugar stability. 1. Regulation of glucose metabolism: Insulin promotes the uptake and utilization of glucose by tissues and cells, accelerates the synthesis of glycogen from glucose, stores it in liver and muscle, inhibits gluconeogenesis, promotes the conversion of glucose into fatty acids, and stores it in adipose tissue, resulting in the decrease of blood sugar level. When insulin is deficient, the blood sugar concentration will increase, and if it exceeds the renal sugar threshold, sugar will appear in urine, causing diabetes. 2. Regulation of fat metabolism Insulin promotes the synthesis of fatty acids in the liver and then transports them to fat cells for storage. Under the action of insulin, fat cells can also synthesize a small amount of fatty acids. Insulin also promotes glucose to enter fat cells, which can not only synthesize fatty acids, but also convert them into α -glycerophosphate. Fatty acids and α -glycerophosphate form triglycerides, which are stored in fat cells. At the same time, insulin also inhibits the activity of lipase and reduces the decomposition of fat. When insulin is deficient, there will be disorder of fat metabolism, enhanced lipolysis, increased blood lipid, accelerated fatty acid oxidation in the liver, and a large number of ketone bodies will be generated. Because of the disorder in the process of sugar oxidation, ketone bodies can not be well treated, leading to ketosis and acidosis. 3. Regulation of protein Metabolism Insulin promotes the synthesis of protein, which can be used in all aspects of protein synthesis: ① promoting the transmembrane transport of amino acids into cells; ② It can accelerate the process of nuclear replication and transcription, and increase the production of DNA and RNA; ③ Acting on ribosomes, accelerating the translation process and promoting the synthesis of protein; In addition, insulin can inhibit protein decomposition and liver gluconeogenesis. Because insulin can enhance the synthesis process of protein, it can also promote the growth of the body. However, when insulin acts alone, its effect on growth is not very strong, and it can only play an obvious role when it works with auxin. Recent research shows that almost all cells in the human body have insulin receptors on their cell membranes. Insulin receptor has been successfully purified and its chemical structure has been clarified. Insulin receptor is a tetramer composed of two α subunits and two β subunits. The α subunit is composed of 7 19 amino acids, which is completely exposed outside the cell membrane and is the main site of receptor binding to insulin. α and α subunits, α and β subunits are bonded by disulfide bonds. The β subunit consists of 620 amino acid residues and is divided into three domains: N-terminal 194 amino acid residues extend out of the membrane; In the middle is a transmembrane domain containing 23 amino acid residues; The C-terminal extends to the inside of the membrane, which is the protein kinase domain. Insulin receptor itself has tyrosine protein kinase activity, and insulin binding to the receptor can activate the enzyme, phosphorylating tyrosine residues in the receptor, which plays a very important role in transmembrane information transmission and cell function regulation. A series of reactions caused by insulin binding to receptors are quite complex and unclear.

Edit the regulation of insulin secretion in this paragraph.

1. The role of blood sugar Blood sugar concentration is the most important factor in regulating insulin secretion. When the blood sugar concentration increases, insulin secretion increases obviously, thus promoting blood sugar reduction. When the blood sugar concentration drops to the normal level, insulin secretion quickly returns to the basic level. Under the stimulation of persistent hyperglycemia, insulin secretion for 5 minutes can be divided into three stages: within 5 minutes after hyperglycemia, insulin secretion can be increased by about 10 times, mainly due to the release of hormones stored in B cells, so the duration is not long, and insulin secretion will be reduced by 50% after 5- 10 minutes; After the blood sugar rises 1.5 min, the insulin secretion increases for the second time, reaching the peak in 2-3 hours, lasting for a long time, and the secretion rate is much higher than that in the first period, which mainly activates the insulin synthase system of B cells and promotes synthesis and release. If hyperglycemia lasts for about a week, insulin secretion can be further increased, which is caused by long-term hyperglycemia stimulating B cell proliferation. 2. The role of amino acids and fatty acids Many amino acids have the effect of stimulating insulin secretion, among which arginine and lysine have the strongest effect. When the blood sugar concentration is normal, the content of amino acids in the blood increases, which can only slightly stimulate the secretion of insulin, but if the blood sugar increases, excessive amino acids can double the insulin secretion caused by blood sugar. When Una's fatty acids and ketone bodies increase greatly, it can also promote insulin secretion. 3. The effects of hormones on insulin secretion are as follows: ① Gastrointestinal hormones, such as gastrin, secretin, cholecystokinin, gastrin inhibitory peptide, etc., all have the effects of promoting insulin secretion, but the first three can only promote insulin secretion at pharmacological doses, unlike a physiological stimulus, only GIP or glucose-dependent insulin stimulating peptides. GIP is a linear polypeptide composed of 43 amino acids secreted by duodenal and jejunal mucosa. Experiments show that GIP can stimulate insulin secretion in a glucose-dependent manner. The hyperglycemia caused by oral glucose and GIP secretion are parallel, and this parallel relationship leads to rapid and obvious insulin secretion, which exceeds the insulin secretion reaction caused by intravenous glucose. Someone sucked glucose into the mouth of mice and injected GIP antiserum. As a result, the blood sugar concentration increased, but the insulin level did not. Therefore, GIP can be considered as the main incretin stimulating factor secreted by the intestinal mucosa during the absorption of glucose by the small intestine. Besides glucose, intestinal absorption of amino acids, fatty acids and hydrochloric acid can also stimulate the release of GIP. Some people call the relationship between gastrointestinal hormones and insulin secretion "intestinal-islet axis", which has important physiological significance, so that insulin secretion has increased while food is still in the intestine, preparing for the utilization of sugar, amino acids and fatty acids to be absorbed from the small intestine; ② Auxin, cortisol, thyroid hormone and glucagon can indirectly stimulate insulin secretion by increasing blood glucose concentration, so long-term high-dose application of these hormones may lead to B cell failure and diabetes; ③ The growth inhibition of islet D cells can at least inhibit the secretion of insulin and glucagon through paracrine, and glucagon can also directly stimulate B cells to secrete insulin. Fig. 1 1-22 Distribution of islet cells and interaction between hormones → Prompt promotion →→→ Prompt inhibition of GIH: somatostatin 4. Neuroregulatory islets are innervated by vagus nerve and sympathetic nerve. Stimulation of vagus nerve can directly promote insulin secretion through acetylcholine acting on M receptor. Vagus nerve can also indirectly promote insulin secretion by stimulating the release of gastrointestinal hormones. When sympathetic nerve is excited, norepinephrine acts on α2 receptor to inhibit insulin secretion.

Edit this glucagon

Human glucagon is a linear polypeptide composed of 29 amino acids, with a molecular weight of 3485, which also comes from the cleavage of a macromolecular precursor. The concentration of glucagon in serum is 50- 100ng/L, and its half-life in plasma is 5- 10min. Glucagon is mainly inactivated in liver and degraded in kidney.

Edit the main function of this pancreatic hyperglycemia.

Contrary to the action of insulin, glucagon is a hormone that promotes catabolism. Glucagon has a strong role in promoting glycogen decomposition and gluconeogenesis, thus significantly increasing blood sugar. 1mol/L hormone can rapidly decompose 3× 106mol/L glucose in glycogen. Glucagon activates hepatocyte phosphorylase through cAMP-PK system and accelerates glycogen decomposition. The enhancement of gluconeogenesis is because hormones accelerate the entry of amino acids into hepatocytes and activate the enzyme system related to gluconeogenesis. Glucagon can also activate lipase, promote lipolysis, strengthen fatty acid oxidation and increase ketone body production. The target organ of glucagon that produces the above metabolic effects is the liver. These effects will disappear when the liver is removed or the blood flow to the liver is blocked. In addition, glucagon can also promote the secretion of insulin and islet somatostatin. Pharmacological dose of glucagon can increase cAMP content in myocardial cells and enhance myocardial contraction.

Edit the regulation of glucagon secretion in this paragraph.

There are many factors affecting glucagon secretion, and blood glucose concentration is an important factor. When blood sugar decreases, pancreatic secretion of glucagon increases; When blood sugar rises, glucagon secretion decreases. The effect of amino acids is opposite to that of glucose, which can promote the secretion of glucagon. Protein powder or intravenous injection of various amino acids can increase glucagon secretion. On the one hand, the increase of amino acids in blood can promote the release of insulin, thus reducing blood sugar, on the other hand, it can also stimulate the secretion of glucagon, which has certain physiological significance for preventing hypoglycemia. Insulin can indirectly stimulate the secretion of glucagon by lowering blood sugar, but the islet secreted by B cells can directly act on neighboring A cells than somatostatin secreted by D cells, and inhibit the secretion of glucagon. Insulin and glucagon are a pair of hormones with opposite effects, and they both form a negative feedback regulation loop with blood sugar level. Therefore, when the body is in different functional states, the molar ratio (I/G) of insulin to glucagon in blood is different. Generally, the I/G ratio is 2.3 under overnight fasting, but it can be reduced to below 0.5 under hunger or long-term exercise. The decrease of the ratio is caused by the decrease of insulin secretion and the increase of glucagon secretion, which is beneficial to glycogen decomposition and gluconeogenesis, maintaining blood sugar level, adapting to the needs of the heart and brain for glucose, being beneficial to fat decomposition and enhancing the energy supply of fatty acid oxidation. On the contrary, after eating or sugar loading, the ratio can rise above 10, which is due to the increase of insulin secretion and the decrease of glucagon secretion. In this case, the effect of islet ratio is the main one.

Edit this segment of islet B cells.

In the past few years, great progress has been made in the discussion of the etiology of 1 diabetes in the academic circles of diabetes, but its pathogenesis and etiology have not been clarified in detail. Since 1980s, the autoimmune theory of 1 type diabetes has been established. According to various comprehensive studies, it is known as an autoimmune disease mediated by T lymphocytes. Islet B cells are selectively destroyed by autoimmune attack, and the function of islet B cells is damaged, and insulin secretion is absolutely or relatively insufficient. 1 type diabetes is caused by susceptible individuals and environmental factors. Glutamate decarboxylase

Edit this paragraph specifically.

[1] (gad) is an enzyme protein existing in human body. There are two isozymes, GAD65 and GAD67, which are widely distributed in human islets and brain tissues. Their effects on islets are paracrine and autocrine signals. 1982, Beakeskov found 64K protein autoantigen in B cells, and was diagnosed as GAD 8 years later. 1990, Beakkeskov proved that the 64K antibody in the serum of patients with type 1 diabetes was GAD autoantibody. Therefore, GAD is the key antigen of 1 diabetes caused by destroying islet cells. At present, it is believed that the pathogenesis is related to virus infection. Diabetes caused by virus was reported by Stang more than 100 years ago (1864). In recent years, especially the study of Coxsackie B virus (CVB) confirmed that the onset season of diabetes is consistent with the epidemic season of Coxsackie B virus, and the antibody titer of patients' serum neutralizing CVB is the highest. This virus is the environmental pathogenic factor of IDDM. It may destroy islet B cells directly by inducing cell lysis, or induce autoimmune reaction of B cells by causing inflammatory reaction of islet. At present, it is believed that there is a kind of "molecular similarity theory", which was first put forward by Oldstone in 1987. He believes that if the antigenic determinants recognized by T cells are similar in sequence or structure to the host's own protein, then T cells activated by environmental antigens will lead to autoimmune diseases. In 1993, Kaufman also suggested that the similarity of molecular structure may be the basis of cross-immune reaction between virus and B cells. It has been confirmed that the sequence of six amino acids in the nonstructural protein 2C of CVB is the same as that of the autoantigen GAD65 in islet B cells (mammary gland-cereal-valerian -lai- cereal -lai). The experiment confirmed that the antibody has cross-reaction with GAD65 antigen and 2C protein, and the protein containing homologous series can stimulate the increase of peripheral blood lymphocytes in patients with IDDM. Varela-Calvino's research shows that 2C protein of CVB is an important factor to induce IDDM. School et al. also confirmed that the same sequence between 2C protein of GAD65 and CVB and proinsulin plays an important role in stimulating and maintaining the autoimmune response of IDDM. More and more scholars believe that molecular similarity theory is the most likely way to induce viral infection and cause autoimmune diseases. Study on vitamin D and its receptor [3]. Clinically, vitamin D has been widely used. Studies have confirmed that vitamin receptor (VDR) is widely distributed in human body, which can regulate human immune system. Its deficiency may lead to the occurrence and development of IDDM. VitD is the environmental factor and genetic factor of IDDM, and the mutation of VDR gene may also be the genetic risk factor of IDDM. Ban et al. found that VDR FokI polymorphism was related to the positive antibody of Japanese IDDM GAD65. VDR plays an important role in the reaction of lymphocytes to microorganisms, and may be involved in autoimmune reactions, such as the production of GAD65 antibodies. In the case of VitD deficiency or VDR gene mutation, T cell-mediated autoimmune reaction may be caused, and the balance of Th 1/Th2 may be destroyed, so that the islet antigen-specific Th 1 cell is preferentially expressed, and Th 1 cell secretes interferon (INF)-γ transforming growth factor (TGF)-β and interleukin (IL)-2 are activated. VitD can inhibit the production of Th 1 cells and Th 1 cells, correct the imbalance of Th 1/Th2, increase the concentration of blood Ca 2+ and increase insulin secretion. The role of CD38 antibody in the pathogenesis of IDDM [4] Human CD38 is a transmembrane glycoprotein, which has enzyme activity, participates in signal transcription and is distributed in hematopoietic system as a surface receptor. Physiologically, it plays an important role in the process of insulin secretion by B cells, but if CD38 produces autoantibodies or gene mutation, it can aggravate the damage of islet B cells and promote the occurrence of diabetes. Anti-CD38 autoantibodies combined with CD38 can induce the release of inflammatory cytokines IL- 1, IL-6 and tumor necrosis factor (TNF), leading to islet inflammation. CD38 was also expressed on the nuclear membrane of B cell nucleus. Anti-CD38 autoantibodies can activate Ca in the nucleus and trigger gene transcription, expression and apoptosis. Anti-CD38 autoantibodies have no obvious relationship with known IA (islet cell antibody), IA-2A (tyrosine phosphatase antibody) and GADA (glutamic acid decarboxylase antibody). Studies have shown that it has attracted people's attention as a new marker of cellular autoimmunity. It opens up a new field of vision for studying the pathogenesis of diabetes. The problem of insulin autoantibodies in 1 [5] The study of insulin autoantibodies shows that the cellular immunity and humoral immunity of 1 diabetic patients are abnormal, and there are many autoantibodies in IDDM patients, including islet cell antibody (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylation antibody (GADA) and tyrosine phosphatase antibody (IA-2A). There are islet autoantibodies in the serum of IDDM patients, but the level of C-peptide in diabetic patients with positive antibodies decreased significantly at the onset or within several years, leading to islet dependence. It has been proved that GAD, IA-2 and insulin are all target antigens of autoantibodies and target molecules of autoreactive T cells. Pancreatitis caused by cellular immune response can directly destroy B cells, but whether islet autoantibodies are the cause or result of B cell injury is inconclusive. Ziegler and others confirmed that islet autoantibodies were obtained, and antibody positive species gradually increased. Sabbah et al. found that many autoantibodies are positive and can react to accelerate the process of B cell destruction. According to Yoon's experimental results, Harala thinks GAD is the only initial antigen that causes the disease. Mechanism of Interleukin Action in T2T 1 Type Diabetes [6] The cellular immunity and humoral immunity of T2T1Type Diabetes are abnormal. In recent years, it has been found that the abnormal changes of IL-2 and IL-6 play an important role in autoimmune reaction. Studies have shown that T 1DM patients' lymphocytes are activated, and a large amount of IL-2 is secreted, which causes autoimmune reaction through the following ways: (1) directly acts on cytotoxic T lymphocytes; (2) making B lymphocytes proliferate and differentiate to produce antibodies; (3) Increase the activity of NK cells and cause self-tissue damage. Some experiments suggest that IL-2 does not directly damage islet B cells, but acts on the immune system. The decrease of IL-2 inhibitor in serum of patients with autoimmune diseases is related to some defects of T lymphocytes. IL-6 is the terminal differentiation factor of B lymphocytes, which can promote the secretion of IgA, IgG and IgM by B lymphocytes, and also significantly increase the killing activity of peripheral cytotoxic T lymphocytes in the presence of IL-2. IL-6 acts on B lymphocytes in differentiation stage, promoting B lymphocytes to produce antibodies, making them in a state of high reaction, which is manifested by the production of patients' own antibodies. To sum up, the etiology and pathogenesis of 1 diabetes is related to the above factors. Under the combined action of genetic and environmental factors, it stimulates the autoimmune system in the body, which eventually leads to the progressive apoptosis and destruction of islet B cells, thus causing absolute or relative deficiency of insulin secretion. From the research of the above scholars, it shows that the immunological factors of 1 diabetes are being gradually explored and fully affirmed. This has certain clinical significance for the prevention and treatment of 1 diabetes in the future. The hormone secreted by islet D cells of somatostatin is called somatostatin. Somatostatin is a small peptide molecular hormone containing 14 amino acids. This hormone is also involved in regulating glucose metabolism, which can inhibit the secretion of glucagon and insulin by islets.