GLP-1 (7-37)Nws yog ib qho tshuaj hormone secreted los ntawm glucagon hlwb uas txhawb nqa glycogen tawg thiab gluconeogenesis. Nws yog polypeptide muaj li ntawm 30 amino acids, nrog ib tug molecular hnyav ntawm kwv yees li 3700 Daltons. Raws li lub cev nqaij daim tawv, Tib neeg glucagon zoo li peptide-1 muaj nyob rau hauv daim ntawv monomeric thiab muaj ob qhov tseem ceeb amino acid sequences: lub A- saws los ntawm 1st mus rau 20th amino acids thiab B-chain muaj li ntawm 21st mus rau 30th amino acids. Yooj yim rau yaj hauv dej, nws solubility hauv dej yog 2 mg / mL. Tsis tas li ntawd, Tib neeg glucagon zoo li peptide-1 tuaj yeem yaj hauv phosphate tsis nrog pH ntawm 7.4. Phosphate tsis muaj kev ruaj ntseg zoo thiab tuaj yeem nyob ruaj khov rau ob peb hnub ntawm chav tsev kub. Txawm li cas los xij, nyob rau hauv acidic tej yam kev mob, Tib neeg glucagon zoo li peptide-1 yog yooj yim degraded los ntawm enzymes. Hauv nws lub xeev ntuj, nws yog linear peptide. Tab sis nyob rau hauv tej yam kev mob, lub voj voog yuav tsim los ntawm disulfide bonds.
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Customized Bottle Caps Thiab Corks:
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C.F |
C151H228N40O47 |
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E.M |
3354 |
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M.W |
3356 |
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m/z |
3355 (100.0%), 3356 (81.1%), 3354 (61.2%), 3357 (36.4%), 3356 (14.8%), 3357 (12.0%), 3358 (10.6%), 3357 (9.7%), 3355 (9.0%), 3358 (7.8%), 3357 (7.2%), 3358 (6.8%), 3356 (5.9%), 3358 (5.4%), 3359 (3.5%), 3359 (3.3%), 3356 (2.6%), 3359 (2.2%), 3357 (2.1%), 3356 (1.8%), 3355 (1.6%), 3359 (1.6%), 3357 (1.5%), 3358 (1.4%), 3359 (1.2%), 3355 (1.1%), 3360 (1.1%), 3357 (1.1%), 3358 (1.1%), 3360 (1.0%), 3359 (1.0%) |
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E.A |
C, 54.05; H, 6.85; N, 16.70; O, 22.41 |
GLP-1 (7-37)yog cov saw tawv nqaij uas muaj 31 amino acids, hydrolyzed los ntawm pancreatic glucagon secreted los ntawm L-cells nyob rau hauv txoj hnyuv. Nws yog stimulated los ntawm lub cev stimulation ntawm cov zaub mov ntawm txoj hnyuv thiab tso tawm ntawm neurotransmitters / nroj paj paj thaum pub mis. Nws muaj cov haujlwm ntawm kev txhawb nqa cov tshuaj insulin secretion, inhibiting pancreatic glucagon secretion, thiab tswj kev noj zaub mov.
Glucagon-zoo li Peptide-1 (GLP-1), cov tshuaj hormones hauv plab hnyuv endogenous, ua lub luag haujlwm tseem ceeb hauv kev tswj lub cev hnyav los ntawm ntau lub hom phiaj. Nws tsuas yog ua rau ntawm hypothalamus los hloov cov cim qab los noj mov thiab inhibits plab hnyuv ua haujlwm xws li plab hnyuv plab thiab gastric acid secretion, uas synergistically txo cov khoom noj thiab ua kom poob phaus. Hauv qab no yog ib qho kev piav qhia ntawm nws cov txheej txheem kev cai tseem ceeb.
Hypothalamic Regulation: Sib npaug Satiety thiab tshaib plab
Lub hypothalamus yog lub hauv paus rau lub zog homeostasis. GLP-1 hla cov ntshav- lub hlwb teeb meem thiab lub hom phiaj tseem ceeb hypothalamic nuclei, tswj ob tus neeg tawm tsam neuron. Nws qhib POMC neurons los zais -MSH, uas xa cov cim muaj zog satiety; ib txhij, nws inhibits NPY / AgRP neurons, txo cov kev tshaib kev nqhis-txhawb cov cim. Qhov kev tswj hwm ob txoj cai no rov ua kom qab los noj mov, txo qis kev mob siab rau noj.
Txoj Cai Gastrointestinal: Inhibiting Gastric Functions
GLP-1 ua rau lub plab zom mov qeeb qeeb los ntawm kev tswj cov nqaij ntshiv plab, ua kom cov zaub mov hauv plab ntev dua kom muaj kev noj qab haus huv tas li. Qhov no txhawb kev satiety thiab txo qhov nruab nrab ntawm cov khoom noj txom ncauj. Nws kuj tseem txo cov kua qaub hauv plab los ntawm inhibiting gastrin tso tawm thiab parietal cell kev ua, txo qis cov as-ham thiab txo tag nrho lub zog kom tsawg.
Synergistic nyhuv rau poob phaus
GLP-1 qhov hnyav-txo cov nyhuv yog nyob ntawm kev sib koom ua ke ntawm kev tswj hwm kev noj qab haus huv hypothalamic thiab kev cuam tshuam ntawm plab hnyuv. Cov txheej txheem no sib sau ua ke txo cov zaub mov kom tsawg thiab nqus lub zog. Kev sim tshuaj xyuas tau lees paub tias kev siv GLP-1 analogs mus ntev tau ua tiav qhov hnyav thiab ruaj khov (5-10% ntawm qhov hnyav hauv qab) hauv cov tib neeg rog, nrog rau kev txhim kho hauv cov ntsuas metabolic zoo li ntshav qabzib, qhia txog nws cov txiaj ntsig kho mob hauv kev tswj kev rog.
Cov nyhuv ntawm Tib neeg glucagon zoo li peptide-1 ntawm cov ntshav siab: Atrial Urinary Skin (ANP) nyob ntawm txoj kev.
GLP-1 ua haujlwm ntawm qhovGLP-1 (7-37)receptor ntawm atrial myocardial hlwb, nce CAMP theem thiab txhawb Epac2 membrane translocation, yog li kho qhov kev tso tawm ntawm ANP. ANP kho cov leeg nqaij ntawm tes so thiab vasodilation los ntawm CGMP, txhawb nqa lub raum tawm ntawm sodium hauv cov zis, thiab thaum kawg ua rau txo qis ntshav siab. Kev cuam tshuam ntawm Tib neeg glucagon zoo li peptide-1 ntawm cov ntshav lipids:
Ua rau lub siab
nce daim siab B oxidation, txo cov rog tsim thiab fatty acid kom tsawg, yog li txo daim siab steatosis, ua kom cov haujlwm macrophage, ua kom cov cholesterol clearance, thiab thaum kawg txo VLDL tsim.
Ua haujlwm ntawm cov hnyuv
Kev tswj cov lipid absorption thiab chylomicron synthesis ntawm lub plab hnyuv cell los ntawm kev tswj cov noob muaj feem xyuam rau cov roj cholesterol thiab fatty acid uptake thiab thauj.
Kev cuam tshuam tsis ncaj
Tib neeg glucagon zoo li peptide-1 nkoos insulin secretion hauv pancreas, uas tuaj yeem cuam tshuam adipocyte lipolysis, ua rau txo qis hauv cov rog rog dawb thiab txo qis hauv plab hnyuv chylomicron. Tib neeg glucagon zoo li peptide-1 inhibits plab hnyuv plab thiab txo cov plab hnyuv glycerol, yog li txo qis chylomicron ntau lawm.
Tib neeg glucagon zoo li peptide-1 inhibits qhov nqus ntawm glycerol los ntawm kev ua haujlwm ntawm plab hnyuv siab rau lub paj hlwb, cuam tshuam nrog kev qhia ntawm cov noob koom nrog hauv cov rog tiam thiab glycerol khaws cia, thiab txo qis kev tsim ntawm chylomicrons. Tib neeg glucagon zoo li peptide-1 muaj kev cuam tshuam zoo rau lub raum, thiab ua kom lub raum ua haujlwm ntawm lub raum. diuresis thaum sodium overload thiab ntim expansion tshwm sim, txo cov dej thiab sodium tuav hauv npua.
Endogenous GLP-1 yog degraded sai heev los ntawm DPP-IV enzyme (dikinase) nyob rau hauv lub cev, nrog ib nrab-lub voj voog ntawm tsuas yog 2 feeb, yuav tsum tau tas li infusion rau 24 teev kom tau raws li kev kho mob xav tau kev kho mob.
Txhawm rau kov yeej qhov teeb meem no, GLP-1 analogue (Liraglutide) tau dhau los ua ob qhov kev hloov kho raws li cov qauv endogenous ntawm GLP-1: ib qho ntxiv 16 carbon palmitic acid sab saw ntawm txoj hauj lwm 26, thiab lwm qhov hloov arginine nrog lysine ntawm txoj hauj lwm 34. Qhov kev hloov pauv ntawm cov ntaub so ntswg ua rau nws qeeb qeeb. degradation los ntawm DPP-V enzymes. Lub neej ib nrab ncua mus rau 13 teev, thiab cov nyhuv hypoglycemic tuaj yeem kav ntev li 24 teev, Meanwhile, vim 97% homology ntawm Liraglutide thiab tib neeg GLP-1, nws tsis tshua muaj cov tshuaj tiv thaiv kab mob thiab tau siv dav hauv kev kho mob.
Lub mechanism ntawmGLP-1 (7-37)Ntshav qabzib concentration dependent hypoglycemia yog cuam tshuam nrog kev vam khom ntawm cov protein kinase A (PKA) ntawm cov piam thaj concentration los ntawm kev kaw cov ion channel.
Tib neeg glucagon zoo li peptide-1 khi rau GLP-1 receptor ua ke nrog G protein ntawm B cell membrane, ua kom adenosine cyclase (AC) los ntawm kev txhawb nqa G protein. Tom qab ua kom tiav, adenylate cyclase (AC) tuaj yeem ua rau ATP los tsim cov cyclic adenosine monophosphate (CAMP). CAMP yog tus xa xov thib ob uas txhawb nqa kev tso tawm ntawm insulin los ntawm B hlwb los ntawm GLP-1, thiab thaum cov concentration ntawm AMP nce, nws ua rau cov protein kinase A (PKA).
Kev kaw ntawm cov poov tshuaj ion channels los ntawm PKA nyob ntawm cov piam thaj hauv cov ntshav, thiab tsuas yog thaum ATP / ADP qib nce mus txog qib qee qhov tuaj yeem kaw cov poov tshuaj ion channel, yog li pab txhawb txoj kev pib. Tom qab ua rau txoj kev ua kom muaj zog, cell membrane depolarization ua rau txoj kev nthuav dav. GLP-1 tuaj yeem ua ntxiv rau txoj hauv kev nthuav dav, ua kom qeeb ntawm cov calcium ion channel tsis ua haujlwm, ua kom lub sijhawm ncov ntawm calcium ion concentration, nce calcium ion concentration, txhawb cov tshuaj insulin uas muaj vesicle exocytosis, thiab pab txo cov ntshav qab zib. Thaum cov piam thaj concentration txo qis, qhov piv ntawm ATP rau ADP txo qis, ua rau nws tsis txaus los kaw cov poov tshuaj. Qhov qis qis ntawm ATP rau ADP kuj tseem tiv thaiv PKA los ntawm kev ua haujlwm ntawm cov poov tshuaj. Txoj kev pib ntawm cov poov tshuaj tsis tuaj yeem tshwm sim, yog li insulin tsis tuaj yeem tso tawm. Yog li, GLP-1 lub peev xwm los nkag siab txog kev hloov pauv hauv cov piam thaj hauv cov ntshav yog qhov tseeb cov piam thaj hauv cov ntshav nce qib ntawm insulin secretion.
GLP-1(7-37)yog 31-amino- cov kua qaub hauv plab incretin hormone (tseem hu ua tib neeg glucagon-zoo li peptide-1). Nws cov khoom siv tshuaj npog ntau yam xws li cov qauv molecular, lub cev lub cev, solubility, stability, thiab reactivity. Cov kev ntsuam xyuas hauv qab no yuav tsom mus rau cov yam ntxwv tseem ceeb ntawm cov tshuaj lom neeg.
Molecular Structure thiab Composition
Amino Acid Sequence
Cov amino acid ntu ntawm GLP-1 (7-37) yog:
HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG (ib leeg- tsab ntawv abbreviation) Los yog
Nws-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr{{12}Gly{12}Lu{12} 5}}Gln-Ala-Ala-Lys-Glu-Ph-Ile- Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (peb -cov ntawv luv luv).
Cov kab ke no txuas nrog los ntawm cov ntawv cog lus amide, tsim cov kab hluav taws xob polypeptide, uas muaj ntau lub polar (xws li Ser, Thr) thiab tsis yog -polar (xws li Leu, Val) amino acids, muab nws cov yam ntxwv amphipathic.
Molecular formula thiab molecular hnyav
Cov mis mos molecular: C₁₅₁H₂₂₈N₄₀O₄₇
Molecular Luj: 3355.72 Da (qhov loj npaum li cas yog 3355.666 Da, qhov chaw sib txawv yuav txawv me ntsis vim yog txoj kev suav).
Nws qhov hnyav molecular yog nruab nrab thiab belongs rau cov khoom sib xyaw peptide.
pH tus nqi thiab kev faib tawm
GLP-1 (7-37) muaj ntau yam acidic (xws li Glu, Asp) thiab cov ntsiab lus (xws li Arg, Lys) amino acids. Lub isoelectric point (pI) yuav tsum nyob ze nruab nrab (tus nqi tshwj xeeb yuav tsum tau sim txiav txim siab). Raws li physiological pH (7.4), cov molecule nqa cov nqi tsis zoo thiab tuaj yeem khi rau lub cell membrane lossis receptor los ntawm kev sib cuam tshuam electrostatic.
Lub cev lub xeev thiab tsos
Qhov tshwm sim
GLP-1(7-37) feem ntau yog cov hmoov dawb dawb rau cov hmoov dawb uas muaj purity ntau dua lossis sib npaug li 95% (kuaj los ntawm HPLC). Cov khoom lag luam siab purity yog nyob rau hauv cov hmoov zoo sib xws thiab tsis muaj impurities pom lossis pob.
Ceev thiab Refractive Index
Qhov ceev: Tus nqi kwv yees yog 1.48 ± 0.1 g / cm³ (qhov hloov pauv me ntsis tuaj yeem tshwm sim vim qhov sib txawv ntawm cov ntaub ntawv siv lead ua los ntawm ntau qhov chaw).
Refractive Index: Tus nqi kwv yees yog 1.660 (xam raws li cov qauv molecular simulation).
Cov kev txwv no cuam tshuam txog qib ntawm kev ntim khoom kaw hauv nws lub xeev ruaj khov thiab nws cov khoom kho qhov muag.
Solubility thiab Solvent Selection
Dej Solubility
Solubility ntawm GLP-1 (7-37) hauv dej yog tsawg (< 0.1 mg/mL), but it can be significantly improved by adjusting the pH:
acidic tej yam kev mob (pH ≈ 1): Solubility ntau dua los yog sib npaug rau 50 mg/mL (14.90 mM) hauv 0.1 M HCl. Ultrasound- pabcuam kev kho mob tuaj yeem txhim kho solubility ntxiv.
Cov xwm txheej nruab nrab: Solubility txo qis. Cov dej ntshiab yuav tsum tsis txhob siv rau kev npaj ncaj qha.
Solubility hauv Organic Solvents
80% acetic acid / dej tov: Solubility Ntau dua los yog sib npaug rau 10 mg / mL (2.98 mM), haum rau kev sim xav tau kev pabcuam organic hnyav.
DMSO: Solubility <1 mg/mL (yuav luag insoluble lossis me ntsis soluble). Siv ceev faj kom tsis txhob cuam tshuam rau kev ua haujlwm ntawm polypeptide.
Solubility Optimization Strategies
Kev hloov kho pH: acidic tej yam kev mob (xws li HCl) tuaj yeem rhuav tshem cov kab mob sib xyaw ua ke hydrogen, nce solubility.
Ultrasound-Assisted Solubilization: Txo kev sib sau los ntawm kev cuam tshuam ntawm lub cev, txhim kho kev ua kom zoo dua.
Stepwise Dissolution: Dissolve nyob rau hauv ib tug me me ntawm acidic tov ua ntej, ces dilute mus rau lub hom phiaj concentration.
Kev ruaj ntseg thiab kev cia khoom
Thermal stability
GLP-1(7-37) is temperature-sensitive. High temperatures (>25 degree) tuaj yeem ua rau degradation lossis aggregation. Qhov ntsuas kub tau pom zoo yog -20 degree, thiab rov ua kom khov thiab thawing yuav tsum zam.
Lub teeb ruaj khov
Nws yuav tsum tau muab khaws cia rau hauv qhov tsaus ntuj (xws li siv lub raj mis xim av lossis aluminium ntawv ci qhwv). Kev raug rau lub teeb yuav ua rau cov duab- oxidation tshwm sim, ua rau cov qauv molecular puas.
Tshuaj stability
pH cuam tshuam: Nws yog qhov ua rau hydrolysis nyob rau hauv pH huab (xws li cov kua qaub uas muaj zog lossis muaj zog hauv paus), poob nws cov khoom lom.
Oxidation rhiab heev: Nws muaj ntau yam oxidizable amino acids (xws li Met, Trp), thiab yuav tsum tau ua nyob rau hauv inert gas (xws li nitrogen) tiv thaiv.
Reactivity Activity thiab Biological Function Correlation
Receptor khi txoj haujlwm
GLP-1(7-37) exerts nws cov nyhuv los ntawm activating GLP-1 receptor (GLP-1R). N-terminal (His⁷-Glu²¹) thiab C-terminal (Lys²⁸-Gly³⁷) thaj tsam yog qhov tseem ceeb rau kev sib khi receptor. Kev hloov kho tshuaj (xws li fatty acid saw txuas) tuaj yeem ua rau nws lub neej ib nrab, tab sis cov chaw tseem ceeb yuav tsum nyob twj ywm.
Enzyme hydrolysis rhiab heev
Nws yooj yim degraded los ntawm dipeptidyl peptidase-4 (DPP-4), ua rau inactivation. Lub ntuj GLP-1(7-37) muaj ib nrab-lub neej ntawm tsuas yog 1-2 feeb thiab yuav tsum tau hloov kho cov qauv (xws li fatty acid sab saw ntawm liraglutide) kom ruaj khov.
Kev txheeb xyuas bioactivity
Nws lub peev xwm los txhim kho insulin secretion yog txheeb xyuas los ntawm kev sim ntawm tes (xws li INS-1 hlwb) lossis cov qauv tsiaj (xws li kev sim hyperglycemic clamp), lees paub qhov kev sib raug zoo ntawm cov tshuaj lom neeg thiab kev ua haujlwm lom neeg.
FAQ
Leej twg tsis tuaj yeem noj GLP-1?
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Cov neeg mob uas muaj mob xws li kev nyuaj siab lossis kev noj zaub mov tsis zoo yuav xav tau kev txiav txim siab ntxiv ua ntej pib kho GLP-1. Qee zaum, cov tshuaj no tuaj yeem ua rau muaj teeb meem kev puas siab puas ntsws, yog li nws yog ib qho tseem ceeb los daws cov xwm txheej no nrog rau kev kho qhov hnyav.
Ozempic ua dab tsi rau koj lub ntsej muag?
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Kev poob phaus sai sai ua tiav nrog Ozempic tuaj yeem txo lub ntsej muag ntim, ua rau cov tawv nqaij xoob, kab thiab wrinkles, lossis qhov pom ntawm hollowed ua qhov tseem ceeb. Muaj ob peb yam los xav txog ntawm koj qhov kev poob phaus los pab tiv thaiv Ozempic ntsej muag. Lub cev qhuav dej tuaj yeem ua rau muaj qhov tsis zoo.
Txoj kev pheej yig tshaj kom tau GLP-1 yog dab tsi?
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Nrog Insurance: Yog tias koj txoj kev npaj them rau GLP-1s, koj cov nyiaj them poob haujlwm yuav yog koj qhov kev xaiv pheej yig tshaj. FDA- Pom zoo (Nyiaj Ntsig): Generic liraglutide tam sim no yog tus pheej yig tshaj glp 1 agonist uas yog tag nrho FDA- pom zoo thiab muaj rau cov neeg mob them nyiaj ntsuab.
Cim npe nrov: glp-1 (7-37) cas 106612-94-6, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom