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1 kits (10 Vials)
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▎ Tsarin GLP-2
Source: PubChem |
Jeri: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diacid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Tsarin kwayoyin halitta: C 225H 348N 48O68 Nauyin Kwayoyin: 4813 g/mol Lambar CAS: 2023788-19-2 Kamfanin CID na PubChem: 163285897 Synonyms: Zepbound; Munjaro |
▎ GLP-2 Bincike
Menene asalin bincike na GLP-2?
GLP-2 magani ne na polypeptide na roba, kuma haɓakarsa ya samo asali ne daga zurfin fahimtar iyakokin GLP-1 masu karɓar agonists na yanzu a cikin jiyya na nau'in 2 na metabolism metabolism da kiba. Kodayake GLP-1 agonists masu karɓa sun riga sun nuna kyakkyawan aiki a cikin sarrafa glucose na jini da asarar nauyi, masana kimiyya sun gano cewa yayin da suke kunna mai karɓar GLP-1, tasirin su akan mai karɓar GIP yana da rauni sosai, wanda har zuwa wani lokaci yana iyakance tasirin warkewar magungunan. Don haka, ƙungiyar bincike da haɓakawa ta himmatu wajen haɓaka sabon nau'in magani wanda zai iya kunna duka GIPR da GLP-1R a lokaci guda, a cikin bege na samun ƙarin ingantaccen kuma ingantaccen sarrafa glucose na jini da sarrafa nauyi [1] .
A lokacin bincike da ci gaban tsarin GLP-2, masana kimiyya sun gudanar da babban adadin bincike na asali da gwaji na asibiti. Da farko, a cikin matakin bincike na farko, an kimanta halayen magunguna na GLP-2 ta hanyar gwaje-gwajen dabbobi, kuma an tabbatar da yuwuwar sa a cikin sarrafa glucose na jini da asarar nauyi. Sakamakon ya nuna cewa GLP-2 na iya rage matakin glucose na jini sosai a cikin samfuran dabbobi kuma yana da kyau a sarrafa nauyi. Waɗannan tabbataccen binciken sun kafa tushe mai ƙarfi don gwaje-gwajen asibiti na gaba.
Daga baya, GLP-2 ya shiga matakin gwaji na asibiti, gami da gwajin lokaci I, II, da III. A cikin gwajin lokaci na, aminci, juriya, da halayen magunguna na miyagun ƙwayoyi an kimanta su musamman, kuma sakamakon ya nuna cewa GLP-2 yana da aminci mai kyau da haƙuri. Gwajin kashi na II ya ƙara bincika inganci da amincin allurai daban-daban na GLP-2 a cikin marasa lafiya da ke da nau'in 2 na metabolism, kuma da farko an ƙaddara kewayon tasirin sa. Mafi mahimmancin gwaji na asibiti na III, kamar su jerin binciken SURPASS, sun rufe adadi mai yawa na marasa lafiya tare da nau'in ciwon sukari na 2. Sakamakon ya nuna cewa GLP-2 ya fi agonists masu karɓa na GLP-1 na yanzu, kamar GLP-1, wajen rage glucose na jini da nauyi. Wannan sakamakon ci gaba ya ba da goyan bayan shaida mai ƙarfi don aikace-aikacen tallan GLP-2 [1].
GLP-2 polypeptide ne wanda ya ƙunshi amino acid guda 39, wanda a cikinsa aka gyara amino acid ɗin daidaikun don inganta kwanciyar hankali da ingancinsa. Wannan tsari na musamman yana ba GLP-2 damar haɗa tasirin hormones na incretin guda biyu, GIP da GLP-1, cikin kwayoyin halitta guda ɗaya, da kunna masu karɓar hormone waɗanda ke cikin sarrafa glucose na jini ta hanyar tsarin aiki biyu. Musamman, GLP-2 na iya yin aiki akan duka pancreas da tsarin juyayi na tsakiya. A gefe guda, yana haɓaka ƙwayar insulin kuma yana hana sakin glucagon, ta yadda ya kamata ya rage glucose na jini yadda ya kamata; a daya bangaren kuma, ta hanyar jinkirta zubar da ciki da kuma kara yawan koshi, yana rage sha'awa da cin abinci, don haka yana samun nasarar sarrafa nauyi. Wannan tsarin aikin dual yana ba GLP-2 fa'idodi na musamman a cikin jiyya na nau'in 2 na metabolism da kiba, yana ba marasa lafiya ƙarin zaɓi na jiyya [1].
Menene tsarin aikin GLP-2?
GLP-2 yana rage yawan glucose na jini ta hanyoyi da yawa da ke aiki tare, kamar haka: Kunna mai karɓar GLP-1: GLP-2 yana ɗaure ga mai karɓar GLP-1 akan ƙwayoyin β na pancreatic, yana kwaikwayon tasirin GLP-1 na halitta. GLP-1 hormone ne da aka samar a cikin hanji kuma yana da mahimmanci don kiyaye glucose homeostasis 2. Yana iya inganta haɓakar insulin, haɓakar insulin, da fahimtar glucose, da kuma rage ƙwayar glucagon don inganta koshi da hana ci 2.
Wannan kunnawa na iya haɓaka ƙwayar insulin. Insulin shine babban hormone mai rage glucose na jini a cikin jiki, wanda zai iya ƙara ɗauka da amfani da glucose ta hanyar sel, ta yadda zai rage matakan glucose na jini. A cikin marasa lafiya da ke da nau'in metabolism na nau'in 2, ƙwayar insulin ba ta isa ba ko kuma hankalin sel ga insulin ya ragu, wanda ke haifar da haɓakar glucose na jini. GLP-2 yana ƙara haɓakar insulin ta hanyar kunna mai karɓar GLP-1, wanda ke taimakawa wajen haɓaka sarrafa glucose na jini. A lokaci guda, kunna mai karɓar GLP-1 na iya hana sakin glucagon. Glucagon yawanci yana haɓaka glycogenolysis da gluconeogenesis a cikin yanayin azumi, yana haɓaka samar da glucose na jini. Ta hanyar hana tasirin glucagon, GLP-2 yana ƙara rage tushen glucose na jini, wanda ke taimakawa wajen sarrafa glucose na jini [2] (Anonymous, 2023).
Kunna mai karɓar GIP: GLP-2 yana aiki akan mai karɓar GIP a lokaci guda. Bayan kunnawa, yana iya haɓaka ji na insulin da ɓoyewa. Mai karɓar GIP yana samuwa a cikin kyallen takarda kamar ƙwayoyin β na pancreatic. Bayan kunnawa, ta hanyar tafiyar da siginar siginar intracellular, haɓakar insulin ya karu, kuma ana inganta amsawar sel zuwa insulin, ta haka ne mafi inganci rage yawan glucose na jini 2. GLP-2 shine na farko-in-aji dual glucagon-kamar peptide-1 da glucose-dogara da glucose-dogara da insulinotropic polypeptide (GIP) analogues na manya da marasa lafiya da motsa jiki da kuma motsa jiki da magani. 2. GLP-2 shine tsarin sinadarai na roba wanda ya dogara da jerin GIP, wanda ya ƙunshi peptide 39-amino acid. Yana kara samar da insulin, yana rage fitar da glucagon ta hanyar dogaro da glucose, yana rage azumi da matakan glucose na jini, yana inganta wadatuwa, yana rage nauyi, yana jinkirta fitar da ciki.
Wannan tasirin agonist mai karɓar mai karɓa na biyu yana sa GLP-2 ya fi tasiri wajen haɓaka ƙwayar insulin da hana sakin glucagon fiye da GLP-1 agonists mai karɓa ɗaya [2].
Jinkirta zubar da ciki da karuwar satiety: GLP-2 na iya jinkirta zubar da ciki, tsawaita lokacin zama na abinci a cikin ciki, rage yawan sha na abinci, don haka guje wa karuwa mai yawa a cikin glucose na jini bayan cin abinci. A cikin bincike na asali da na asibiti, tasirin GLP-2 akan zubar da ciki yana kama da na GLP-1 agonists mai karɓa. A cikin berayen da ke haifar da abinci, ƙimar jinkirin zubar da ciki ta hanyar GLP-2 yayi kama da na GLP-1, amma waɗannan mummunan tasirin hanawa suna ɓacewa bayan makonni 2 na jiyya. A cikin mahalarta tare da kuma ba tare da nau'in ciwon sukari na 2 ba, GLP-2-1-mako-mako (≥5 da ≥4.5mg, bi da bi) yana jinkirta zubar da ciki bayan kashi ɗaya. A cikin mahalarta masu lafiya, an rage wannan tasirin bayan yawancin allurai na GLP-2 ko dulaglutide [3] .
A lokaci guda kuma, yana iya yin aiki akan tsarin juyayi na tsakiya, ƙara yawan gamsuwa, da rage ci da abinci. Ta hanyar sarrafa cin abinci, a kaikaice yana taimakawa wajen sarrafa matakan glucose na jini, musamman dacewa da matsalar kiba sau da yawa tare da marasa lafiya tare da nau'in ciwon sukari na 2, kuma yana taimakawa haɓaka juriya na insulin da yanayin rayuwa gaba ɗaya [2].
Haɓaka haɓakar insulin da ƙwayar lipid: An gano GLP-2 don haɓaka matakin adiponectin, wanda shine adipocytokine mai alaƙa da hankalin insulin. Ƙara yawan adadin adiponectin yana taimakawa wajen inganta haɓakar insulin, yana sa sel su zama masu kula da insulin, don haka mafi inganci da amfani da glucose, yana rage glucose na jini [2]..
Bugu da kari, GLP-2 kuma na iya inganta bayanin martabar lipid kuma yana da tasirin kariya akan lafiyar zuciya da jijiyoyin jini. GLP-2 an tabbatar da cewa yana iya inganta hawan jini, rage ƙananan ƙarancin lipoprotein (LDL) cholesterol da triglycerides [4] .Wannan yana ƙara goyan bayan fa'idodin fa'ida a cikin sarrafa glucose na jini.
Bincike mai alaƙa
Inganci akan sarrafa nauyi a cikin marasa lafiya tare da kiba da nau'in 2 metabolism:
Yawancin nazarin asibiti sun tabbatar da tasirin asarar nauyi: A cikin binciken mai suna 'SURMOUNT-2', wannan gwaji shine lokaci na 3, makafi biyu, bazuwar, gwajin sarrafa wuribo da aka gudanar a cikin ƙasashe bakwai. Manya (shekaru ≥18 shekaru) tare da ma'auni na jiki (BMI) na 27 kg / m² ko sama da glycated haemoglobin (HbA₁c) na 7 - 10% an ba da izini don karɓar allurar subcutaneous na GLP-2 (10mg ko 15mg) ko placebo na makonni 72. Sakamakon ya nuna cewa a cikin mako na 72, yawan asarar nauyi a cikin GLP-2 10mg da 15mg shine -12.8% da -14.7%, bi da bi, yayin da a cikin rukunin placebo ya kasance -3.2%. Matsakaicin bambance-bambancen jiyya na GLP-2 10mg da 15mg idan aka kwatanta da placebo sune maki -9.6 kashi da maki -11.6, bi da bi, duka biyun suna da mahimmancin ƙididdiga (p＜0.0001). Bugu da ƙari, ƙarin marasa lafiya da aka yi wa magani tare da GLP-2 sun kai iyakar asarar nauyi na 5% ko fiye (79 - 83% vs 32%) [5] (Garvey WT, 2023). A cikin binciken 'SURMOUNT-2', matsakaicin matsakaicin nauyi shine 100.7 kg, BMI shine 36.1 kg/m², kuma HbA₁c ya kasance 8.02%. Bayan makonni 72 na jiyya, GLP-2 ba kawai rage kiba sosai ba har ma ya taka rawa mai kyau a sarrafa glucose na jini [5].
Tasirin haɓakawa akan neuropathy masu alaƙa da metabolism:
Wasu nazarin sun nuna cewa glucagon-like peptide 1 agonists (GLP1-RAs) na iya rage haɗarin lalata a cikin marasa lafiya tare da nau'in ciwon sukari na 2 ta hanyar inganta ƙwaƙwalwar ajiya, koyo, da kuma shawo kan rashin fahimta. A matsayin dual glucose-dependent insulin polypeptide agonist agonist (GIP-RA) / GLP-1RA, GLP-2 an yi nazari don tasirin sa akan alamomin ci gaban neuronal (CREB da BDNF), apoptosis (BAX / Bcl2 rabo), bambanta (pAkt, MAP2, GAP43, da AGBL4), da insulin juriya (GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1, GLUT1). Neuroblastoma cell line (SHSY5Y). Sakamakon a karon farko ya jaddada rawar da GLP-2 ke takawa wajen kunna hanyar pAkt/CREB/BDNF da ɓangarorin sigina na ƙasa, da kuma ingancin sa a cikin neuroprotection. Hakanan ya nuna cewa GLP-2 na iya magance tasirin da ke da alaƙa da hyperglycemia da juriya na insulin a matakin neuronal. Saboda haka, GLP-2 na iya inganta neurodegeneration da ke haifar da hyperglycemia kuma ya shawo kan juriya na insulin na neuronal, yana ba da sababbin fahimta game da haɓakar cututtukan da ke da alaƙa da metabolism [6]. .
Ci gaban bincike a cikin jiyya na nau'in 2 metabolism:
Wasu nazarin sun nuna cewa GLP-2, a matsayin sabon nau'in maganin hypoglycemic, ya zama agonist na GIP/GLP-1R na farko da aka amince da shi don maganin metabolism a cikin Amurka. An tabbatar da cewa yana da tasirin rage yawan glucose na jini da asarar nauyi a cikin manyan gwaje-gwaje na asibiti da yawa, kuma akwai shaidar cewa yana da babban tasiri a cikin kariyar zuciya. Bugu da ƙari, ra'ayin peptides na roba ya buɗe yawancin yuwuwar da ba a san su ba don GLP-2. Gwaje-gwajen da ke gudana (NCT04166773) da shaidu sun nuna cewa ya zama magani mai ban sha'awa a fagen cututtukan hanta maras barasa (NAFLD), renal da neuroprotection, da dai sauransu [7]..
Sakamakon dogon lokaci na T irzepatide akan lafiyar zuciya:
GLP-2 na iya rage haɗarin cututtukan zuciya ta hanyar haɓaka asarar nauyi. Wani binciken yayi nazarin tasirin GLP-2 akan kiba da cututtukan cututtukan zuciya a cikin manya na Amurka [8] . Binciken ya gano cewa tsakanin manya na Amurka da suka cancanci maganin GLP-2, bayan jiyya tare da 15mg na GLP-2, an kiyasta cewa 70.6% da 56.7% na manya suna da asarar nauyi na ≥15% da ≥20% na mutane, wanda ke nufin adadin kiba ya ragu. 58.8%. A cikin mutanen da ba tare da cututtukan zuciya ba, kimanin shekaru 10 na hadarin cututtukan zuciya ya ragu daga 10.1% kafin magani zuwa 7.7% bayan jiyya, yana nuna cikakkiyar raguwar haɗarin 2.4% da raguwar haɗarin dangi na 23.6%, wanda ke nufin cewa za a iya hana 2 miliyan abubuwan cututtukan cututtukan zuciya a cikin shekaru 10.
A ƙarshe, GLP-2 labari ne mai dual agonist na GIP da masu karɓar GLP-1 kuma yana da mahimmanci a cikin kula da nau'in ciwon sukari na 2 da kiba. Yana iya inganta haɓakar ƙwayar insulin yadda ya kamata, yana hana ƙwayar glucagon, daidaita glucose na jini daidai, rage haɗarin rikitarwa, haɓaka aikin ƙwayoyin β pancreatic, da jinkirta ci gaban metabolism. Har ila yau, yana da tasirin kariya akan tsarin zuciya da jijiyoyin jini. A wajen maganin kiba, yana iya rage cin abinci yadda ya kamata, rage sha’awa, kara koshi, taimaka wa masu kiba su rage kiba, da rage hadarin da ke da alaka da kiba. Hakanan yana iya haɓaka juriya na insulin da metabolism na lipid. Bugu da ƙari, yana nuna yuwuwar a cikin maganin cututtukan da ke da alaƙa da rashin daidaituwa na rayuwa irin su steatohepatitis mara-giya, ciwo na bacci na bacci, da gazawar zuciya, kuma yana iya haɓaka haɓakar alamomin rayuwa da yawa a lokaci guda, yana ba da cikakken tsarin kulawa. Hanyar gudanar da allurar sa sau ɗaya a mako-mako ya dace don amfani kuma yana iya haɓaka ƙa'idodin kulawar marasa lafiya. Ta hanyar sarrafa glucose da nauyi yadda ya kamata da rage haɗarin rikice-rikice, yanayin jikin marasa lafiya na iya ingantawa sosai, ana iya haɓaka iya ayyukansu na yau da kullun da ingancin rayuwarsu, za a iya ƙara amincewa da shawo kan cututtuka, za a iya sauke nauyin tunaninsu, kuma za a iya inganta yanayin zamantakewar su.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Dokta William T. Garvey fitaccen malami ne kuma mai bincike da ke da alaƙa da manyan cibiyoyi masu daraja, ciki har da Jami'ar Alabama a Birmingham, Jami'ar Aston, da Cibiyar Kiwon Lafiyar Tsohon Soja ta Birmingham. Asalin iliminsa da ƙwarewar ƙwararrun ƙwararrun ƙwararrun ƙwararrun fannoni a cikin fannonin likitanci da kimiyya. Dokta Garvey ya ba da gudummawa mai mahimmanci ga fannonin ilimin endocrinology da metabolism, abinci mai gina jiki da abinci mai gina jiki, biochemistry da ilmin kwayoyin halitta, da kuma magani na gabaɗaya da na ciki, tare da mai da hankali kan tsarin zuciya da jijiyoyin jini. An san aikinsa sosai kuma an girmama shi sosai, musamman ana kiransa da Babban Mai Binciken Bincike a cikin Yankin Cross-Field na 2023 da 2024, yana nuna babban tasiri da tasirin bincikensa akan al'ummar kimiyya.
Dokta Garvey's bincike sha'awa da gwaninta ya fadada zuwa sassa daban-daban na cututtuka na rayuwa da sarrafa su. Ya kasance mai himma sosai a cikin nazarin metabolism metabolism, kiba, da rikice-rikicen da ke tattare da su, da nufin buɗe sabbin dabarun warkewa da haɓaka sakamakon haƙuri. Ayyukansa sun ƙunshi bincike na kimiyya na asali, gwaje-gwaje na asibiti, da nazarin fassarar fassarar, ƙaddamar da rata tsakanin binciken dakin gwaje-gwaje da aikace-aikacen likita na ainihi. Ta hanyar bincike mai zurfi, Dokta Garvey ya ba da gudummawa ga zurfin fahimtar hanyoyin da ke tattare da rikice-rikice na rayuwa kuma ya taimaka wajen tsara ka'idodin asibiti da ka'idojin magani a fagen ilimin endocrinology da metabolism. Dr. William T. Garvey an jera shi a cikin ambaton ambaton [5].
