▎ GLP-2 Bincike
Menene asalin bincike na GLP-2?
Haɓakawa na GLP-2, maganin polypeptide na roba, ya samo asali ne daga sanin iyakokin GLP-1 agonists masu karɓa a cikin kula da nau'in metabolism na nau'in 2 da kiba. Ko da yake GLP-1 agonists masu karɓa sun yi fice a cikin sarrafa glucose na jini da asarar nauyi, masana kimiyya sun gano raunin su na masu karɓar GIP iyakance tasirin warkewa. Don haka, ƙungiyoyin bincike sun yi niyya don haɓaka sabbin magunguna waɗanda ke iya kunna GIPR da GLP-1R don ƙarin ingantaccen sarrafa glycemic da sarrafa nauyi [1].
An gudanar da gwaje-gwajen gwaje-gwaje masu yawa da na asibiti a yayin ci gaba.
Nazarin dabba na preclinical sun kimanta kaddarorin pharmacodynamic, yana tabbatar da yuwuwar sa a cikin sarrafa glycemic da asarar nauyi. Gwajin asibiti na mataki na farko an tantance aminci, juriya, da magunguna, yana nuna kyakkyawan aminci.
da juriya. Gwaje-gwajen lokaci na II sun kara bincika inganci da aminci a allurai daban-daban a cikin nau'in 2 na marasa lafiya na metabolism, da farko suna ƙayyadadden jeri mai inganci. Gwaje-gwajen Pivotal Phase III kamar jerin SURPASS, wanda ya haɗa da manyan ƙungiyoyi na nau'in 2 na marasa lafiya na metabolism, sun nuna GLP-2 da mahimmanci fiye da agonists masu karɓa na GLP-1 na yanzu wajen rage glucose na jini da nauyi, yana ba da tabbataccen shaida don aikace-aikacen talla [1].
Ya ƙunshi amino acid 39 tare da gyare-gyaren tsari don haɓaka kwanciyar hankali da inganci, tsarinsa na musamman yana haɗa ayyukan GIP da GLP-1 a cikin ƙwayar ƙwayar cuta guda ɗaya, kunna masu karɓar hormone waɗanda ke cikin sarrafa glycemic ta hanyoyi biyu.
A gefe guda, yana aiki akan pancreas don haɓaka haɓakar insulin da hana sakin glucagon don rage glucose na jini; a gefe guda, yana aiki akan tsarin kulawa na tsakiya don jinkirta zubar da ciki, ƙara yawan jin dadi, da rage yawan ci da abinci don sarrafa nauyi. Wannan tsarin dual yana ba da fa'idodi na musamman na GLP-2 a cikin kula da nau'in 2 metabolism da kiba, yana ba marasa lafiya ƙarin cikakkun zaɓuɓɓukan warkewa [1].
Menene tsarin aikin GLP-2?
GLP-2 yana rage glucose na jini ta hanyoyi da yawa:
Kunna masu karɓar GLP-1: Haɗe zuwa masu karɓar GLP-1 akan ƙwayoyin β pancreatic, yana kwaikwayon GLP-1 na halitta don haɓaka haɓakar insulin, ɓoyewa, da fahimtar glucose yayin da ake rage ƙwayar glucagon don haɓaka gamsuwa da hana ci. A cikin nau'in 2 na marasa lafiya na metabolism, kunna masu karɓar GLP-1 yana ƙara haɓakar insulin don ingantaccen sarrafa glycemic, yayin da hana sakin glucagon yana ƙara rage tushen glucose na jini, yana taimakawa tsarin glycemic [2]..
Kunna masu karɓar GIP: Yin aiki akan masu karɓar GIP, kunnawa yana haɓaka haɓakar insulin da ɓoyewa. Masu karɓar GIP sun fi kasancewa a cikin kyallen takarda kamar ƙwayoyin β na pancreatic, kuma kunnawa ta hanyar siginar siginar intracellular yana ƙara haɓakar insulin kuma yana inganta amsawar salula ga insulin don ingantaccen rage glucose na jini [2] . Wannan ciwon mai karɓa na dual receptor yana sa GLP-2 ya fi tasiri wajen haɓaka ƙwayar insulin da hana sakin glucagon fiye da masu karɓar GLP-1 guda ɗaya [2] .
Jinkirta Zubar da Ciki da Ƙarfafa Satiety: Yana jinkirta zubar ciki, yana tsawaita riƙe abinci a cikin ciki don jinkirin sha na gina jiki da kuma guje wa spikes na glucose na jini bayan cin abinci. A halin yanzu, yin aiki akan tsarin juyayi na tsakiya don haɓaka satiety yana rage ci da cin abinci, musamman fa'ida ga kiba sau da yawa hade da nau'in 2 metabolism, yana taimakawa haɓaka juriya na insulin da yanayin rayuwa gaba ɗaya [3].
Ingantaccen Insulin Sensitivity da Lipid Ciwon sukari: Haɓaka matakan adiponectin-wani abu mai kitse da ke da alaƙa da hankalin insulin-yana taimakawa haɓaka haɓakar insulin, yana ba da damar sel don ɗauka da inganci da amfani da glucose don rage glucose na jini [2] (Anonymous, 2023). Hakanan yana haɓaka bayanan martaba na lipid, tare da yuwuwar tasirin kariya akan lafiyar zuciya da jijiyoyin jini, bayan an nuna shi don haɓaka hawan jini da rage LDL cholesterol da triglycerides [3].
Menene karatun da ya dace?
GLP-2 yana nuna tasiri mai mahimmanci a cikin sarrafa nauyi don masu kiba da nau'in 2 na marasa lafiya na metabolism. A cikin binciken SURMOUNT-2, wani mataki na 3, makafi biyu, bazuwar, gwajin sarrafa wuribo da aka gudanar a cikin ƙasashe bakwai, manya masu shekaru ≥18 shekaru tare da BMI ≥27 kg / m² da HbA1c 7-10% an bazu don karɓar GLP-2 subcutaneous mako-mako (10 MG ko 15 mg) ko placebo na makonni 72. Ta mako na 72, yawan asarar nauyi sun kasance -12.8% da -14.7% a cikin GLP-2 10 MG da 15 MG tare da -3.2% a cikin rukunin placebo, tare da bambance-bambancen jiyya na -9.6 da -11.6 maki maki idan aka kwatanta da placebo (p <0.0001). Bugu da ƙari, ƙarin marasa lafiya da aka yi wa GLP-2 sun sami ≥5% asarar nauyi (79-83% vs. 32%) (Garvey WT, 2023). Tare da ma'anar ma'anar ma'auni 100.7 kg, BMI 36.1 kg/m², da HbA1c 8.02%, makonni 72 na jiyya tare da GLP-2 ba kawai rage girman nauyi ba amma kuma inganta sarrafa glycemic [4] .
A cikin inganta haɓakar cututtukan cututtukan cututtukan ƙwayar cuta, bincike ya nuna GLP1-RAs na iya rage haɗarin lalata a cikin nau'in 2 na marasa lafiya na metabolism ta hanyar haɓaka ƙwaƙwalwar ajiya, koyo, da shawo kan matsalar rashin fahimta. A matsayin GIP-RA / GLP-1RA dual, GLP-2 an yi nazari a cikin layin kwayoyin neuroblastoma (SHSY5Y) don tasirinsa akan ci gaban neuronal (CREB da BDNF), apoptosis (RAX / Bcl2 rabo), bambancin (pAkt, MAP2, GAP43, da AGBL4), da kuma insulin juriya (GLUT1, 4ORLU.GLUT1) An samo shi don yin tasirin neuroprotective ta hanyar kunna hanyar pAkt/CREB/BDNF da siginar sigina na ƙasa, magance hyperglycemia- da tasirin juriya na insulin a matakin neuronal. Don haka, GLP-2 na iya haɓaka haɓakar haɓakar hyperglycemia-induced neurodegeneration da shawo kan juriya na insulin neuronal, yana ba da sabbin fahimta don sarrafa neuropathy masu alaƙa da metabolism [5].
A cikin nau'in 2 na ci gaban jiyya na metabolism, GLP-2, wani sabon magani na hypoglycemic, ya zama farkon wanda aka yarda da GIP/GLP-1R agonist don metabolism a cikin manyan gwaje-gwajen asibiti da yawa na Amurka sun tabbatar da tasirin rage glycemic da asarar nauyi, tare da yuwuwar kariyar zuciya. Ma'anar peptides na roba ya buɗe yawancin yuwuwar da ba a bayyana ba don GLP-2. Gwaje-gwaje da shaidun da ke ci gaba da nuna cewa magani ne mai ban sha'awa ga cututtukan hanta mai ƙiba (NAFLD), kariya ta koda, da neuroprotection [6].
Game da tasirin dogon lokaci akan lafiyar zuciya da jijiyoyin jini, GLP-2 na iya rage haɗarin cututtukan zuciya (CVD) ta haɓaka asarar nauyi. Wani binciken da ke nazarin tasirin GLP-2 akan kiba da abubuwan CVD a cikin manya na Amurka ya gano cewa daga cikin waɗanda suka cancanci jiyya na GLP-2, an ƙididdige maganin 15 MG don cimma ≥15% da ≥20% asarar nauyi a cikin 70.6% da 56.7% na manya, bi da bi, fassara zuwa raguwar kiba 58.8%. A cikin mutane ba tare da CVD ba, haɗarin CVD na shekaru 10 ya ragu daga 10.1% 'kafin-jiyya' zuwa 7.7% 'bayan magani,' yana wakiltar cikakken raguwar haɗarin 2.4% da raguwar haɗarin dangi na 23.6%, mai yuwuwar hana abubuwan CVD miliyan 2 [7].
Kammalawa
A taƙaice, GLP-2 labari ne mai dual agonist na GIP da masu karɓar GLP-1, yana riƙe da mahimmanci a cikin kula da nau'in 2 metabolism da kiba. Yana inganta haɓakar ƙwayar insulin yadda ya kamata, yana hana sakin glucagon, kuma yana daidaita glucose na jini daidai, yana rage haɗarin haɗari yayin haɓaka aikin β-cell na pancreatic da jinkirta ci gaban metabolism, tare da tasirin cardioprotective. A cikin maganin kiba, yana rage yawan abinci yadda ya kamata, yana hana ci, yana ƙaruwa, yana taimakawa rage nauyi, kuma yana rage haɗarin rikitarwa masu alaƙa da kiba yayin haɓaka juriya na insulin da metabolism na lipid. Bugu da ƙari, yana nuna yuwuwar a cikin magance rikice-rikice na rayuwa kamar steatohepatitis mara-giya, ciwo na apnea bacci, da gazawar zuciya, yana ba da cikakkiyar magani ta haɓaka sigogin rayuwa da yawa. Jadawalin allurar sa na sati-sati yana haɓaka dacewa da yarda da haƙuri. Ta hanyar sarrafa glucose na jini yadda ya kamata, rage haɗarin haɗari, da haɓaka yanayin jiki sosai, ayyukan yau da kullun, da ingancin rayuwa, GLP-2 yana haɓaka amincin marasa lafiya game da sarrafa cututtuka, yana rage nauyin tunani, da haɓaka daidaitawar zamantakewa.
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 ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun likitocin 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 [4].
