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Amylin
Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h .... It is co-secreted with insulin from the pancreatic beta cell, β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in Blood sugar level, glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing Postprandial, post-prandial spikes in blood glucose levels. IAPP is processed from an 89-residue coding sequence. Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin. Synthesis ProIAPP consists ...
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Amylin Primary Structure
Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels. IAPP is processed from an 89-residue coding sequence. Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin. Synthesis ProIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence (from N-terminus to C-terminus) is: (MGILKLQVFLIVLSVALNHLKA) TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLNYL ...
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Beta Cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. Function The primary function of a beta cell is to produce and release insulin and amylin. Both are hormones which reduce blood glucose levels by different mechanisms. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting some of their stored insulin and amylin while simultaneously producing more. Primary cilia on beta cells regulate their function and energy metabolism. Cilia deletion can lead to islet dysfunction and type 2 diabetes. Insulin synthesis Beta cells are the only site of insulin synthesis in mammals. As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis, mainly through translational cont ...
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Beta Cells
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. Function The primary function of a beta cell is to produce and release insulin and amylin. Both are hormones which reduce blood glucose levels by different mechanisms. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting some of their stored insulin and amylin while simultaneously producing more. Primary cilia on beta cells regulate their function and energy metabolism. Cilia deletion can lead to islet dysfunction and type 2 diabetes. Insulin synthesis Beta cells are the only site of insulin synthesis in mammals. As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis, mainly through translational cont ...
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Proprotein Convertase 2
Proprotein convertase 2 (PC2) also known as prohormone convertase 2 or neuroendocrine convertase 2 (NEC2) is a serine protease and proprotein convertase PC2, like proprotein convertase 1 (PC1), is an enzyme responsible for the first step in the maturation of many neuroendocrine peptides from their precursors, such as the conversion of proinsulin to insulin intermediates. To generate the bioactive form of insulin (and many other peptides), a second step involving the removal of C-terminal basic residues is required; this step is mediated by carboxypeptidases E and/or D. PC2 plays only a minor role in the first step of insulin biosynthesis, but a greater role in the first step of glucagon biosynthesis compared to PC1. PC2 binds to the neuroendocrine protein named 7B2, and if this protein is not present, proPC2 cannot become enzymatically active. 7B2 accomplishes this by preventing the aggregation of proPC2 to inactivatable forms. The C-terminal domain of 7B2 also inhibits PC2 activi ...
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Type 2 Diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes. In type 1 diabete ...
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Fatty Acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells. History The concept of fatty acid (''acide gras'') was introduced in 1813 by Michel Eugène Chevreul, though he initially used some variant terms: ''graisse acide'' and ''acide huileux'' ("acid fat" and "oily acid"). Types of fatty acids Fatty acids are classified in many ways: by length, by saturation vs unsatura ...
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Tumor Necrosis Factor Alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes. As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation. Suppression of TNFR1 signaling has been important for ...
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Promoter (biology)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Promoters control gene expression in bacteria and eukaryotes. RNA polymerase must attach to DNA near a gene for transcription to occur. Promoter DNA sequences provide an enzyme binding site. The -10 sequence is TATAAT. -35 sequences are conserved on average, but not in most promoters. Artificial promoters with conserved -10 and -35 elements transcribe more slowly. All D ...
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Diabetes (journal)
''Diabetes'' is a monthly peer-reviewed medical journal published since 1952 by the American Diabetes Association. It covers research about the physiology and pathophysiology of diabetes mellitus including any aspect of laboratory, animal or human research. Emphasis is on investigative reports focusing on areas such as the pathogenesis of diabetes and its complications, normal and pathologic pancreatic islet function and intermediary metabolism, pharmacological mechanisms of drug and hormone action, and biochemical and molecular aspects of normal and abnormal biological processes. Diabetes also publishes abstracts presented at the ADA's annual meeting, Scientific Sessions, as a supplement. According to the ''Journal Citation Reports'', the journal has a 2021 impact factor of 9.337, and 5 years impact factor of 10.509 ranking it 8th out of 240 journals in the category "Endocrinology, Diabetes & Metabolism". See also * American Diabetes Association * ''Diabetes Care ''Diabetes ...
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Lipotoxicity
Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. Lipotoxicity is believed to have a role in heart failure, obesity, and diabetes, and is estimated to affect approximately 25% of the adult American population. Cause In normal cellular operations, there is a balance between the production of lipids, and their oxidation or transport. In lipotoxic cells, there is an imbalance between the amount of lipids produced and the amount used. Upon entrance of the cell, fatty acids can be converted to different types of lipids for storage. Triacylglycerol consists of three fatty acids bound to a glycerol molecule and is considered the most neutral and harmless type of intracellular lipid storage. Alternatively, fatty acids can be converted to lipid intermediates like diacylglycerol, ceramides and fatty a ...
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Amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines). Important amines include amino acids, biogenic amines, trimethylamine, and aniline; Inorganic derivatives of ammonia are also called amines, such as monochloramine (). The substituent is called an amino group. Compounds with a nitrogen atom attached to a carbonyl group, thus having the structure , are called amides and have different chemical properties from amines. Classification of amines Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. A ...
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Peptidylglycine Alpha-amidating Monooxygenase
Peptidyl-glycine alpha-amidating monooxygenase is an enzyme that catalyzes the conversion of glycine amides to amides and glyoxylate. The enzyme is involved in the biosynthesis of many signaling peptides and some fatty acid amides. In humans, the enzyme is encoded by the '' PAM'' gene. This transformation is achieved by conversion of a prohormone to the corresponding amide (C(O)NH2). This enzyme is the only known pathway for generating peptide amides, which renders the peptide more hydrophilic. Function This gene encodes a multifunctional protein. It has two enzymatically active domains with catalytic activities - peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). These catalytic domains work sequentially to catalyze neuroendocrine peptides to active alpha-amidated products. The reaction pathway catalyzed by PAM is accessed via quantum tunneling and substrate preorganization. Multiple alternatively spliced t ...
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