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1 kits (10 Vials)
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▎ Tsarin Retatrutid
Source: PubChem |
Jeri: YA⊃1;QGTFTSDYSI-L⊃2;LDKK⁴AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Tsarin kwayoyin halitta: C 221H 342N 46O68 Nauyin Kwayoyin: 4731 g/mol Lambar CAS: 2381089-83-2 PubChem CID: 171390338 Saukewa: LY3437943 |
▎ Binciken Retatrutid
Menene asalin bincike don Retatrutid?
Yawan kiba da nau'in ciwon sukari na 2 na ci gaba da karuwa a duniya, wanda ke haifar da babban kalubalen lafiyar jama'a. Magungunan da suka wanzu guda-ko-biyu suna da iyaka a inganci da aminci. Dangane da ka'idar ƙa'idar daidaitawa mai ma'ana da yawa ta hanyar axis na insulin gastrointestinal, bincike ya bayyana ƙarin ayyuka na GLP-1, GIP, da glucagon a cikin tsarin rayuwa, yana ba da tushe na ka'idar don haɓaka agonists masu karɓa da yawa.
Gina kan ƙwarewar ci gaban ƙwayoyi na biyu-manufa, masu bincike sun ƙirƙira da haɓaka Retatrutid dangane da halayen tsari da hanyoyin sigina na waɗannan masu karɓar sau uku. Ta hanyar kunna GLP-1R, GIPR, da GCGR lokaci guda, yana samun ingantaccen sarrafa glycemic da rage nauyi.
Menene tsarin aiki don Retatrutid?
Mai karɓa Agonism
Retatrutid yana aiki azaman agonist mai karɓar mai karɓar sau uku wanda ke niyya GLP-1, GCGR, da masu karɓar GIP [1].
GLP-1 agonist mai karɓa: GLP-1 shine hormone incretin wanda aka ɓoye ta ƙwayoyin L na hanji. Bayan haɗawa da masu karɓar GLP-1, Retatrutid yana haɓaka haɓakar insulin ta hanyar dogaro da glucose. A lokacin hyperglycemia, Retatrutid yana ɗaure ga masu karɓar GLP-1, yana kunna hanyoyin siginar ƙasa wanda ke haifar da sel na pancreatic don ɓoye insulin da rage matakan glucose na jini. Hakanan yana hana fitowar glucagon kuma yana rage fitowar glucose na hanta, yana ƙara daidaita glucose na jini. GLP-1 agonist mai karɓa kuma yana jinkirta zubar da ciki, yana ƙaruwa, yana rage cin abinci, yana taimakawa sarrafa nauyi [2].
GCGR azabar raɗaɗi: Glucagon yawanci yana aiki yayin hypoglycemia don haɓaka matakan glucose na jini. Ayyukan agonist na Retatrutid akan GCGR yana da rikitarwa. A cikin adipose nama, yana inganta lipolysis kuma yana ƙara yawan iskar oxygen da fatty acid, ta haka yana haɓaka kashe kuzari. A cikin hanta, matsakaicin ƙwannafi na GCGR na iya daidaita matakai kamar gluconeogenesis, inganta aikin hanta. Wannan yana hana wuce gona da iri na gluconeogenesis daga haifar da hyperglycemia yayin da yake kiyaye isasshen glucose na jini don biyan bukatun kuzarin jiki [1].
Agonism mai karɓa na GIP: GIP, wani hormone incretin, yana ɓoye ta ƙwayoyin K a cikin duodenum da jejunum bayan abinci. Agonism mai karɓar GIP na Retatrutid yana haɓaka haɓakar insulin, yana aiki tare da GLP-1 don haɓaka tsarin glucose. Sabanin haka, kunnawa mai karɓar GIP na iya yin tasiri ga metabolism na lipid da daidaiton kuzari. Binciken Brzozowska P ya nuna cewa GIP yana inganta haɓakar glucose da haɗin lipid a cikin adipocytes. Koyaya, a ƙarƙashin tasirin Retatrutid, ana daidaita siginar GIP don haɓaka amfani da makamashi maimakon haɓaka ajiyar kitse kawai, ta haka yana taimakawa sarrafa nauyi [1].
Hoto 1 Hanyoyin aikin Retatrutid [3].
Cikakken Tsarin Tsarin Tsarin Halitta
Dokokin Metabolism na Makamashi: Ta hanyar kunna masu karɓa guda uku da aka ambata a sama, Retatrutid gabaɗaya yana daidaita metabolism na makamashi. Yana haɓaka lipolysis, ƙara shigar da fatty acid cikin mitochondria don β-oxidation da haɓaka kashe kuzari. Yana rage lipogenesis ta hanyar hana shan fatty acid da haɗin triglyceride a cikin adipocytes, ta haka ne ke canza ma'auni na makamashin jiki da ma'aunin kashe kuɗi don sauƙaƙe asarar nauyi. A cikin binciken dabba da suka dace da gwajin asibiti ta Jastreboff AM, gwamnatin Retatrutid ta ƙara yawan kashe kuzarin kuzari da rage yawan kitsen jiki a cikin batutuwa masu kiba [4].
Tsarin Metabolism na Glucose: Retatrutid yana daidaita glucose na jini ta hanyoyi da yawa. Bayan haɓaka haɓakar insulin ta hanyar GLP-1 da kunna mai karɓar GIP, yana tasiri metabolism na hanta ta hanyar daidaita GCGR. Yana hana wuce gona da iri na gluconeogenesis na hanta, yana rage fitowar glucose, kuma a lokaci guda yana haɓaka ɗaukar glucose na nama da amfani, ta haka yana kiyaye matakan glucose na jini na yau da kullun. Wannan yana da mahimmanci musamman ga marasa lafiya masu kiba da nau'in ciwon sukari na 2, yadda ya kamata sarrafa glucose na jini da inganta yanayin ciwon sukari [2].
Dokokin Metabolic Hanta: A cikin hanta, Retatrutid ba wai kawai yana daidaita metabolism na glucose ba amma kuma yana tasiri metabolism na lipid. Yana rage hanta triglyceride kira da tarawa, inganta hanta steatosis, da kuma rike m warkewa darajar ga marasa barasa m hanta cuta (NAFLD). A cikin gwaje-gwajen asibiti da suka haɗa da mahalarta tare da cututtukan hanta mai rauni na rayuwa (MDAFLD), Retatrutid ya rage yawan kitsen hanta, yana nuna ingantaccen tasirin sa akan metabolism na hanta [5].
Tasiri kan Aikin Gastrointestinal
Retatrutid yana jinkirta zubar da ciki ta hanyar kunna masu karɓar GLP-1. Sannu a hankali zubar da ciki yana tsawaita lokacin zama abinci a ciki, yana haifar da gamsuwa mai dorewa da rage cin abinci na gaba. A lokaci guda, yana iya yin tasiri ga ɓoyewar hormone na hanji da motsin hanji, ƙara daidaita tsarin narkewar gastrointestinal da tsarin sha na gina jiki, ta haka gabaɗaya yana shafar ci da kuzari da nauyin jiki [2].
Menene tsarin haɗin kai tsakanin tasirin agonist na Retatrutid akan GLP-1, GCGR, da masu karɓar GIP?
Haɗin kai a cikin Dokar Metabolism Energy
Ƙara yawan Kudaden Makamashi: Kunna GCGR yana haɓaka glycogenolysis da gluconeogenesis don haɓaka matakan glucose na jini. Hakanan yana haɓaka kashe kuzarin kuzari ta hanyar haɓaka metabolism na lipid da kuma hana ci abinci ta hanyar satiety na tsakiya. GLP-1R agonists suna tayar da ɓoyewar insulin kuma suna yin tasirin cardioprotective da neuroprotective, yayin da kuma rage yawan kuzari ta hanyar jinkirta zubar da ciki da kuma hana ci. Yayin da kunna GIPR a cikin adipose nama yana haɓaka tarin lipid, kunnawa ta tsakiya yana rage yawan abinci kuma yana rage kiba. Retatrutid lokaci guda yana kai hari ga waɗannan masu karɓa guda uku, yana kafa sabon ma'auni tsakanin cin makamashi da kashe kuɗi. Wannan ya fi dacewa ya cimma rashi makamashi, ta haka yana sauƙaƙe asarar nauyi.
Daidaita metabolism na lipid: Agonism na GCGR yana haɓaka metabolism na lipid, yayin da kunna GIPR a cikin ƙwayar adipose shima yana tasiri metabolism na lipid. GLP-1R agonists na iya shafar metabolism a kaikaice ta hanyoyi kamar inganta haɓakar insulin. Ayyukan haɗin gwiwar su mafi kyau yana daidaita tsarin kitse, rushewa, da sufuri, rage yawan kitse da inganta rarraba mai. Misali, karatu a cikin marasa lafiya masu kiba ya nuna cewa bayan amfani da Retatrutid na wani lokaci, yawan kitse na jiki ya ragu kuma bayanan martabar lipid sun inganta zuwa wani matsayi, suna ba da shawarar tasirin sa na daidaita tsarin metabolism na mai [6]..
Tasirin Haɗin kai a cikin Tsarin Glucose
Ingantattun Siginin Insulin: GLP-1R agonists suna rage glucose na jini ta hanyar ɗaure ga masu karɓar GLP-1 da haɓaka ƙwayar insulin. Hakanan GIP yana haɓaka ƙwayoyin β-pancreatic don samar da tasirin ɓoyewar insulin kwatankwacin waɗanda cin abinci ya jawo. Retatrutid, wanda ke kunna GLP-1R a lokaci guda da GIPR, yana haɓaka haɓakar insulin sosai, ta haka yana rage matakan glucose na jini yadda ya kamata. Kodayake GCGR yawanci yana da alaƙa da haɓakar glucose na jini, tasirinsa-kamar haɓaka kashe kuzarin kuzari—na iya ba da gudummawa a kaikaice ga kwanciyar hankalin glucose yayin aiki tare da masu karɓa kamar GLP-1R. Bugu da ƙari, haɗaɗɗun amfani da GLP-1 da GCGR zaɓaɓɓu suna magance haɗarin hyperglycemic da GCGR ke haifarwa, yana ba da damar ingantaccen tsarin glucose mai inganci.
Daidaita Glucose Homeostasis: Ƙaƙwalwar haɗakarwa na waɗannan masu karɓa guda uku ya wuce fiye da ɓoyewar insulin don haɗawa da cikakken tsarin glucose homeostasis. Ta hanyar yin tasiri ga ɗaukar glucose, amfani, da adanawa a cikin kyallen takarda da yawa ciki har da hanta, tsoka, da adipose, Retatrutid yana kula da glucose na jini a cikin ingantacciyar kewayo, yana hana haɓaka mai mahimmanci. A cikin binciken da Nicholls S ya yi game da nau'in masu ciwon sukari na 2, gwamnatin Retatrutid ya haifar da raguwa mai yawa a cikin matakan haemoglobin glycated, yana nuna ingantaccen tasirin sa akan sarrafa glycemic na dogon lokaci da kuma nuna tasirin haɗin gwiwa na masu karɓa guda uku a cikin daidaita glucose homeostasis [6]..
Kunna Haɗin kai na Hanyoyin Canja Sigina
Kunna Tafarkin Siginar gama gari: GLP-1R, GCGR, da GIPR da farko sigina ta hanyar sunadaran G (Gαs). Lokacin da Retatrutid yayi aiki akan waɗannan masu karɓa guda uku, yana haɗuwa don kunna hanyoyin da aka raba a ƙasa kamar hanyar cAMP-PKA. Wannan kunnawar hanyar haɗin gwiwa yana haɓaka haɓakar sigina da ƙarfi, haɓaka tasirin tsari akan metabolism na salon salula da ayyukan ilimin lissafi.
Haɓaka hanyoyi daban-daban: Yayin raba hanyoyin gama gari, kowane mai karɓa yana kunna cibiyoyin sadarwar sigina na musamman. Retatrutid yana daidaita waɗannan hanyoyin daban-daban ta hanyar haɗin gwiwa yayin kunna mai karɓa, yana ba da damar daidaita tsarin rayuwa.
Dokokin Haɗin kai na Ayyukan Gastrointestinal
Tasirin Sirrin Hormone na Gastrointestinal: GLP-1R agonists suna motsa siginar GLP-1, yayin da GIPR agonists ke tsara sakin GIP. Wadannan hormones na ciki suna taka muhimmiyar rawa wajen daidaita motsin ciki, narkewa, da sha. Ta hanyar kunna masu karɓa guda ɗaya a lokaci guda, Retatrutid yana ba da ƙarin ƙayyadaddun ƙa'idodi na ɓoyewar hormone na ciki, ta haka yana tasiri aikin gastrointestinal. Yana iya rage saurin sha na gina jiki ta hanyar daidaita yawan zubar da ciki da motsin hanji, yana taimakawa ga nauyi da sarrafa glucose na jini.
Haɓaka Muhalli na Metabolic na Gastrointestinal: Ta hanyar daidaita ƙwayar ƙwayar cuta ta ciki, Retatrutid kuma yana haɓaka yanayin rayuwa a cikin sashin gastrointestinal. Yana haɓaka haɓakawa da haɓakar ƙwayoyin cuta masu amfani kuma yana daidaita aikin shinge na hanji. Waɗannan sauye-sauye na iya ƙara yin tasiri ga yanayin rayuwa gaba ɗaya na jiki. Yin aiki tare tare da tasiri akan metabolism na makamashi da tsarin glucose na jini, waɗannan hanyoyin haɗin gwiwa suna ba da gudummawa ga tasirin warkewa akan kiba da cututtukan da ke da alaƙa.
Menene aikace-aikacen Retatrutid?
Maganin Kiba
Muhimman Tasirin Asarar Nauyi: Gwaje-gwaje na asibiti da yawa suna nuna ingancin Retatrutid a cikin maganin kiba. A cikin Mataki na 2 makafi sau biyu, bazuwar, gwajin sarrafa wuribo ta Jastreboff AM wanda ya shafi manya 338, mahalarta sun karɓi Retatrutid mako-mako a nau'ikan allurai ko placebo na makonni 48. Sakamakon ya nuna cewa a cikin mako 24, ƙungiyar 1mg ta sami asarar nauyi na 7.2%, ƙungiyar haɗin gwiwar 4mg ta rasa 12.9%, ƙungiyar haɗin gwiwar 8mg ta rasa 17.3%, kuma ƙungiyar 12mg ta rasa 17.5%, yayin da ƙungiyar placebo ta rasa kawai 1.6%. A cikin mako 48, ƙungiyar 1mg ta sami matsakaicin asarar nauyi na 8.7%, ƙungiyar haɗin gwiwar 4mg ta rasa 17.1%, ƙungiyar haɗin gwiwar 8mg ta rasa 22.8%, ƙungiyar 12mg ta rasa 24.2%, kuma ƙungiyar placebo ta rasa 2.1%. Daga cikin mahalarta da ke karɓar 4mg, 8mg, da 12mg Retatrutid, 92%, 100%, da 100% sun sami 5% ko mafi girma asarar nauyi, bi da bi. 75%, 91%, da 93% sun sami kashi 10% ko mafi girma asarar nauyi. da 60%, 75%, da 83% sun sami 15% ko asarar nauyi mafi girma, idan aka kwatanta da 27%, 9%, da 2% a cikin rukunin placebo. Waɗannan bayanan suna nuna cikakkiyar ingancin Retatrutid a cikin rage kiba ga marasa lafiya masu kiba [4].
Nau'in Ciwon sukari Na 2
Ingantaccen Kula da Glycemic: Nazarin Lopez DC et al. Retatrutid yana da tasiri mai tasiri akan sarrafa glycemic a cikin nau'in ciwon sukari na 2. A cikin gwaji da ya ƙunshi mahalarta 353, Retatrutid ya rage glycated haemoglobin (HbA1c) da 1.64% idan aka kwatanta da placebo. Wannan yana nuna ingancin Retatrutid a cikin rage matakan glucose na jini a cikin nau'in ciwon sukari na 2, don haka yana ba da gudummawa ga ingantattun sakamakon asibiti [7].
Haɗin Haɗin Kayan Aikin Haɗin Kai: Retatrutid yana aiki akan masu karɓa da yawa, yana ba da fa'ida ta musamman akan agonists masu karɓa guda ɗaya ta hanyar haɗin haɗin agonist. Ba wai kawai yana rage matakan glucose na jini ba ta hanyar haɓaka haɓakar insulin, amma yana haɓaka haɓakar insulin, yana ba da damar ƙwayoyin jiki suyi amfani da insulin yadda ya kamata don cikakken sarrafa glycemic. Sakamakon rage nauyi yana ƙara haɓaka matsayin rayuwa a cikin nau'in masu ciwon sukari na 2, saboda kiba babban abu ne mai haɗari ga yanayin kuma asarar nauyi yana sauƙaƙe ingantaccen sarrafa glucose na jini [5].
Maganin Ciwon Hanta Mai Fattin Da Ba Giya Ba
Rage Hanta Fat Abun ciki: Retatrutid ya nuna ikon rage yawan kitsen hanta a cikin marasa lafiya tare da cututtukan hanta mai rauni na rayuwa (MDAFLD) da abun ciki mai hanta ≥10%. A cikin bazuwar, makafi biyu, gwajin sarrafa wuribo, mahalarta 98 an ba su bazuwar don karɓar allurar subcutaneous na mako-mako na Retatrutid (1mg, 4mg, 8mg, ko 12mg) ko placebo don makonni 48. Sakamakon ya nuna cewa a cikin mako 24, ma'anar canji a cikin abun ciki mai hanta dangane da asali shine -42.9% a cikin rukunin 1mg, -57.0% a cikin ƙungiyar 4mg, -81.4% a cikin ƙungiyar 8mg, da -82.4% a cikin ƙungiyar 12mg, idan aka kwatanta da + 0.3% a cikin rukunin placebo. Waɗannan binciken sun nuna cewa Retatrutid yana rage yawan kitsen hanta, yana nuna yuwuwar ƙimar warkewa ga cututtukan hanta mara-giya [8].
Inganta Ayyukan Metabolic Hepatic: Retatrutid yana haɓaka aikin hanta hanta ta hanyar daidaita makamashi da metabolism na lipid. Yana inganta haɓakar iskar shaka da rushewar ƙwayoyin hanta, yana rage yawan kitse a cikin hanta, yana daidaita martanin kumburi da matakan damuwa a cikin hanta, kuma yana haifar da wani tasirin hanawa akan ci gaban NAFLD, don haka yana kare lafiyar hanta marasa lafiya.
Kammalawa
A matsayin agonist mai karɓa sau uku na GLP-1R/GIPR/GCGR, Retatrutid yana aiwatar da tasirin tsarin rayuwa ta hanyar tsarin haɗin kai mai yawan manufa. Tasirinsa sun haɗa da kunna GLP-1R don hana ci da jinkirta zubar da ciki, don haka rage yawan kuzari; kunna GIPR don haɓaka haɓakar insulin da haɓaka haɓakar insulin; da kunna GCGR don haɓaka lipolysis da kashe kuzari yayin daidaita glucose na hanta da metabolism na lipid don rage tara mai. Wannan haɗin gwiwa sau uku yana samun cikakkiyar tasiri ciki har da iko mai ƙarfi na glycemic, babban asarar nauyi, da haɓaka haɓakar lipid da mai hanta. Babban darajarta ta ta'allaka ne a cikin maganin kiba, samun nasarar rage nauyi mai dogaro da kashi tare da matsakaicin asarar sati 48 na 24.2%. Ga nau'in ciwon sukari na 2, yana rage yawan haemoglobin glycated yadda ya kamata kuma yana inganta glycemia homeostasis. A cikin cututtukan cututtukan hanta mai alaƙa da tabarbarewar rayuwa, yana rage yawan kitsen hanta, yana nuna tasiri mai ƙarfi a cikin rikice-rikice na rayuwa da yawa.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Arun J. Sanyal kwararre ne kan cututtukan hanta kuma mai bincike wanda ya kware kan cututtukan hanta, musamman cutar hanta mai kitse (NAFLD) da marasa giyar steatohepatitis (NASH). Yana da alaƙa da Makarantar Magunguna ta Jami'ar Commonwealth ta Virginia, inda ya kasance mamba tun daga 1989. Sanyal ya rubuta kusan 1,000 wallafe-wallafe a cikin manyan mujallu irin su Cell Metabolism, Nature Medicine, The New England Journal of Medicine, da The Lancet. An ambaci aikinsa sama da sau 104,000, wanda ke nuna gagarumin tasirinsa a fannin ilimin hanta. Cibiyoyin Lafiya na Ƙasa suna ci gaba da ba shi kuɗi tun 1995 kuma shine babban mai binciken tallafin NIH guda huɗu masu aiki. Sanyal kuma an san shi da jagorancinsa a cikin bincike na asibiti da kuma gudummawar da ya bayar wajen samar da hanyoyin magance cututtukan hanta. An jera Arun J. Sanyal a cikin ambato [5].
