GLP-15 MG

▎ Tsarin GLP-1

▎ GLP-1 Bincike

Menene asalin bincike na GLP-1?

GLP-1 analog ne na ɗan adam glucagon-kamar peptide-1 (GLP-1), na rukunin magungunan GLP-1 mai karɓar agonist. GLP-1 wani hormone ne da ke faruwa ta dabi'a wanda ƙwayoyin hanji ke ɓoye bayan cin abinci, wanda ke haɓaka ƙwayar insulin kuma yana hana ƙwayar glucagon don daidaita matakan glucose na jini. Haɓaka GLP-1 ya samo asali ne daga zurfin bincike kan ayyukan ilimin lissafin jiki na GLP-1. GLP-1 yana da ɗan gajeren rabin rayuwa a cikin jiki, kimanin minti 1-2, saboda yana da sauƙin lalacewa ta hanyar dipeptidyl peptidase-4 (DPP-4) enzymes a cikin jiki. Don shawo kan wannan ƙayyadaddun, masana kimiyya sun gyara tsarin GLP-1, suna gabatar da takamaiman maye gurbin amino acid da kuma ƙara ƙungiyoyi masu kariya don haɓaka juriya ga enzymes DPP-4, ta haka ne ya tsawaita tsawon lokacin aiki a cikin jiki ^[1] . A cikin tsarin GLP-1, alanine a matsayi na 8 an maye gurbinsa da α-aminoisobutyric acid (Aib), wanda ba wai kawai inganta kwanciyar hankali na miyagun ƙwayoyi ba amma yana haɓaka ƙarfin ɗaure tare da masu karɓa na GLP-1 ^[2] . Ana ƙara sarkar gefen fatty acid na musamman a cikin C-terminus na GLP-1, wanda aka haɗa da ragowar lysine ta hanyar γ-glutamine, yana ƙara tsawaita rabin rayuwar miyagun ƙwayoyi kuma yana ba da damar allurar sau ɗaya a mako ko kuma a sha da baki sau ɗaya a rana ^[1] . An fara haɓaka GLP-1 bisa ga bincike da gyare-gyare na GLP-1 na halitta, da nufin samar da ingantaccen magani ga marasa lafiya da ciwon sukari na 2 ^{[1, 2]} . Ta hanyar waɗannan haɓakar tsarin, GLP-1 ba wai kawai yana riƙe da ayyukan physiological na GLP-1 ba amma kuma yana haɓaka kaddarorin sa na harhada magunguna, ya zama agonist mai karɓa na GLP-1 mai tsayi mai mahimmanci na asibiti. Haɓaka GLP-1 babbar nasara ce, tana kawo sabbin zaɓuɓɓukan jiyya ga marasa lafiya da nau'in ciwon sukari na 2. Ta hanyar haɓaka tsarin GLP-1 na halitta, yana shawo kan ƙayyadaddun gajeriyar rabin rayuwar sa kuma yana haɓaka kwanciyar hankali na miyagun ƙwayoyi da tsawon lokacin aiki.

Menene tsarin aikin GLP-1?

GLP-1 wani agonist mai karɓar glucagon-kamar peptide-1 (GLP-1) ne mai tsayi, kuma ana samun tsarin aikinsa ta hanyar abubuwa masu zuwa:

Tsarin glucose na jini:

GLP-1 labari ne na GLP-1 agonist mai karɓa (GLP-1RA). Babban tsarin sa shine hana sha'awar abinci ta hanyar hana ci, rage fifikon abinci mai kitse, da daidaita cibiyar ciyar da abinci ta hypothalamic don rage cin abinci. Har ila yau, yana ƙara yawan gamsuwa, yana jinkirta zubar da ciki, da kuma rage motsi na gastrointestinal, ta hanyar samun asarar nauyi. Wannan raguwar nauyi yana haɓaka haɓakar insulin kuma yana taimakawa daidaita matakan glucose na jini ^[3] . GLP-1 yana haifar da asarar nauyi a cikin rodents ta hanyar rarraba hanyoyin jijiyoyi. Nazarin ya nuna yana aiki a kan tushen kwakwalwa, septal nucleus, da hypothalamus amma baya ketare shingen kwakwalwar jini. Maimakon haka, yana hulɗa da kwakwalwa ta hanyar gabobin dawakai da wuraren ventricular-proximal. GLP-1 yana kunna c-Fos a cikin yankuna goma na kwakwalwa, gami da wuraren da aka yi niyya kai tsaye da na baya-bayan nan da na biyu kamar tsakiyar tsakiya na parabrachial ba tare da hulɗar GLP-1R kai tsaye ba. Bincike na atomatik yana ba da shawarar kunnawa ya haɗa da ƙananan ƙwayoyin cuta na parabrachial neurons da ke sarrafa ƙarshen abinci, don haka daidaita glucose na jini ^[4] .

Ka'idojin Gastrointestinal:

GLP-1 yana aiki akan masu karɓar GLP-1 a cikin hanji, ta yin amfani da hanyar jijiyar vagus don daidaita motsin ciki. Yana hana rikicewar antral, yana ƙarfafa tashin hankali na sphincter pyloric, kuma yana tsawaita riƙe abinci na ciki, jinkirta shigarwar duodenal da kuma hana spikes na glucose na jini na baya-bayan nan, yana haifar da ƙarin kwanciyar hankali ^[5] . Bugu da ƙari, GLP-1 yana rinjayar tsakiyar GLP-1 masu karɓa, musamman a cikin arcuate hypothalamic da paraventricular nuclei. Yana hana abubuwa masu motsa jiki kamar neuropeptide Y (NPY) da furotin da ke da alaka da agouti (AgRP), yayin da yake kunna proopiomelanocortin (POMC) neurons don haɓaka alpha-melanocyte-stimulating hormone (α-MSH) ɓoye ^[5] . Wadannan ayyuka suna haifar da gamsuwa, rage yunwa, da rage cin abinci, suna taimakawa sarrafa nauyi da inganta sarrafa glucose na jini a kaikaice.

Kariyar zuciya:

GLP-1 yana haɓaka sakin nitric oxide (NO) da sauran vasodilator daga sel endothelial na jijiyoyin jini, haɓaka vasodilation da kwararar jini. Hakanan yana hana kumburi da damuwa na oxidative, rage lalacewar endothelial da haɗarin atherosclerosis. Ta hanyar hana ci da cin abinci, yana taimakawa rage kiba, yana inganta ciwon sukari, yana rage triglycerides da low-density lipoprotein cholesterol (LDL-C), kuma yana kara yawan lipoprotein cholesterol (HDL-C). Haka kuma, yana iya amfana da hawan jini ta hanyar daidaita hemodynamics na koda da aikin neuroendocrine, rage haɗarin hauhawar jini da rage haɗarin cututtukan cututtukan zuciya ^[6] .

GLP-1 da ƙa'idar rubutun WAT zuwa juyar da BAT da kunna BAT.

Source: PubMed ^[13]

Mabuɗin gwaji da bincike

Dangane da ƙirar tsarin sinadarai da haɓakawa, yayin ƙirar GLP-1, an karɓi hanyar da za a iya jujjuyawa ga albumin don tsawaita lokacin aikin maganin. Ta hanyar ƙayyadaddun ingantacciyar haɗuwar fatty acids da masu haɗin gwiwa, ƙarfin ɗaure zuwa albumin an haɓaka shi yayin kiyaye inganci akan mai karɓar GLP-1 (GLP-1R) (Knudsen LB, 2019).

Dangane da aikace-aikacen miyagun ƙwayoyi, GLP-1 yana da tasirin asarar nauyi. GLP-1 shine glucagon-kamar peptide-1 agonist mai karɓa (GLP-1 RA) tare da dogon kawar da rabin rayuwa, yana barin allurar subcutaneous mako-mako. Sakamakon asarar nauyi yana da ban mamaki. A cikin marasa lafiya da ke da nau'in ciwon sukari na 2 (T2DM), allurar subcutaneous na mako-mako na GLP-1 da alama ya fi tasiri don asarar nauyi fiye da sauran GLP-1RAs na mako-mako. A cikin gwajin neman kashi na II na marasa lafiya masu kiba ba tare da T2DM ba, allurar subcutaneous na GLP-1 kowace rana ya fi tasiri don asarar nauyi fiye da placebo kuma sau ɗaya a rana 3.0mg liraglutide. Rashin nauyi da GLP-1 ya haifar a cikin wannan binciken ya wuce daidaitattun magungunan rigakafin kiba da Hukumar Kula da Magunguna ta Turai (EMA) da Hukumar Kula da Abinci da Magunguna ta Amurka (FDA) suka kafa, ba tare da wasu lamuran aminci ba, wanda ke nuna cewa allurar GLP-1 na subcutaneous sau ɗaya a rana yana da yuwuwar zama maganin asarar nauyi a nan gaba ^[7] .

GLP-1 na iya inganta aikin zuciya kuma ana amfani dashi don maganin cututtukan zuciya. An sanar da sakamakon gwajin STEP-HFpEF, wanda babban adadin antidiabetic glucagon-kamar peptide 1 agonist GLP-1 ya inganta alamun cututtukan zuciya tare da juzu'in cirewa (HFpEF) da rage matakan N-terminal pro-B-type natriuretic peptide (NT-proBNP). Binciken ya gwada tasirin babban maganin GLP-1 akan keɓancewar ɗan adam na haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin haƙƙin ɗan adam kuma ya gano cewa GLP-1 yana ƙara tashin hankali na trabeculae na ɗan adam fiye da sau uku ta hanyar dogaro da kashi, ba tare da ƙara haɓakar arrhythmias ba. Wannan tasirin yana da yuwuwa saboda karuwar sarcoplasmic reticulum Ca2+. Maganin GLP-1 mai girma a cikin marasa lafiya na raunin zuciya na iya inganta aikin atrial kuma don haka rage alamun bayyanar cututtuka ^[8] .

Ana nazarin GLP-1 don maganin steatohepatitis mara-giya (NASH). Tsarinsa na ma'ana ya ba da gudummawa mai yawa don inganta sarrafa glucose na jini, nauyi, hawan jini, lipids, aikin β-cell, da tsarin zuciya da jijiyoyin jini a cikin marasa lafiya da nau'in ciwon sukari na 2. Bugu da ƙari, haɓakar ƙirar baki na GLP-1 na iya ba da ƙarin fa'idodi ga marasa lafiya dangane da yarda da jiyya ^[9] .

Bambance-bambance a cikin Tasirin Rage Nauyi na GLP-1 Gabaɗaya Yawan Jama'a

Illar Rage Nauyi A cikin Manya masu Ciwon Zuciya, Kiba ko Kiba ba tare da ciwon sukari ba: 

A cikin SELECT sakamakon sakamakon cututtukan zuciya, GLP-1 ya rage manyan abubuwan da ke faruwa na zuciya da jijiyoyin jini (MACE) da 20% a cikin manya na 17,604 tare da cututtukan zuciya na zuciya, kiba ko kiba, kuma babu ciwon sukari ^[10] . A cikin wannan ƙayyadaddun ƙayyadaddun ƙayyadaddun bayanai, masu bincike sun bincika tasirin GLP-1 akan nauyi, sakamakon anthropometric, aminci, da jurewa ta hanyar ma'aunin jiki na asali (BMI). Marasa lafiya da ke karɓar GLP-1 sun sami ci gaba da asarar nauyi sama da makonni 65, suna dagewa har zuwa shekaru 4. A cikin makonni 208, GLP-1 ya haifar da raguwar ma'ana mafi girma a cikin nauyi (-10.2%), kewayen kugu (-7.7 cm), da ƙugiya-zuwa tsayi (-6.9%) idan aka kwatanta da placebo (-1.5%, -1.3 cm, da -1.0%, bi da bi; duk kwatancen sun kasance masu mahimmanci na ƙididdiga. GLP-1 yana da alaƙa da ƙananan abubuwan da ba su da kyau ga kowane nau'in BMI (<30, 30 zuwa <35, 35 to <40, and ≥40 kg/m²), GLP-1 yana da ƙananan ƙimar abubuwan da suka faru (abubuwan da suka faru a cikin shekaru 100 na mutum: 43.23, 45.70, da 63.54). 50.48, 49.66, 52.73, da 60.85 don placebo).

Illar Rage Nauyi A cikin Mutane masu Kiba ko Kiba ba tare da ciwon sukari ba:  

Bita na tsari ya kimanta inganci da amincin GLP-1 a cikin masu kiba ko masu kiba ba tare da ciwon sukari ba ^[11] . Wannan bita ya haɗa sakamako daga gwaje-gwajen asibiti da yawa, yana nuna tasirin GLP-1 akan asarar nauyi, sigogi na rayuwa, da sakamakon kiwon lafiya gabaɗaya. Binciken da aka nuna GLP-1 yana da alaƙa da babban asarar nauyi da haɓakawa a cikin ma'aunin kiwon lafiya masu alaƙa da kiba, yana ba da shawarar yuwuwar sa azaman zaɓi mai mahimmanci na jiyya ga marasa lafiya masu kiba. 

Illar Rage Nauyi a cikin Marasa lafiya marasa ciwon sukari (Shaida daga RCT da yawa): 

Gwaje-gwajen da bazuwar bazuwar guda huɗu (RCTs) waɗanda suka haɗa da marasa lafiya tare da ma'auni na asali na 96-105 kg sun kimanta mako-mako 2.4 MG subcutaneous GLP-1 tare da tsarin rayuwa (nasiha, abinci, aikin jiki) don asarar nauyi ^[12] . Ɗaya daga cikin RCT a cikin marasa lafiya marasa ciwon sukari (N = 1,961) ya ruwaito ma'anar asarar 15% (15 kg) vs. 2% (3 kg) tare da placebo bayan makonni 68 (ƙididdiga mai mahimmanci). Yawan marasa lafiya da suka samu ≥5% asarar nauyi shine 86% vs. 32% (lambar da ake buƙata don magance [NNT] = 2), kuma ≥10% asarar nauyi shine 69% vs. 12% (NNT = 2). Rage nauyi a cikin makonni ~ 60. Abubuwan da ba su da kyau na Gastrointestinal (AEs) sun faru a cikin 74% vs. 48% (lambar da ake buƙata don cutar da [NNH] = 3). Kashewa saboda AEs shine 7% vs. 3% (NNH = 25). An lura da irin wannan sakamakon a cikin wani RCT tare da tsaka-tsakin salon rayuwa (N = 611): GLP-1 ya haifar da 16% (17 kg) vs. 6% (6 kg) asarar nauyi. A cikin binciken bincike-bincike na RCT a cikin marasa lafiya marasa ciwon sukari (N = 1,210), mako-mako 2.4 mg GLP-1, 1.0 mg GLP-1, ko placebo ya haifar da asarar nauyi na 10%, 7%, da 3% bayan makonni 68. Matsakaicin samun ≥5% asarar nauyi shine 69% (2.4 mg), 57% (1.0 mg), da 29% (placebo). Don 2.4 MG vs. 1.0 MG, NNT = 9. Bayanan martaba na AE sun kasance daidai da allurai. A cikin kulawar nauyi RCT (N = 803), mahalarta marasa ciwon sukari sun karɓi 2.4 MG GLP-1 mako-mako don makonni 20, sannan an bazu don ci gaba da GLP-1 ko canza zuwa placebo. Bayan makonni 48, masu amfani da GLP-1 sun ci gaba da rasa 8% vs. placebo masu amfani da samun 7%. 

A taƙaice, GLP-1 agonist mai karɓar GLP-1 ne tare da ƙimar aikace-aikacen yanki da yawa. A cikin jiyya na ciwon sukari, yana ɗaure ga masu karɓar GLP-1 don haɓaka haɓakar insulin da hana sakin glucagon, yadda ya kamata ke sarrafa matakan glucose na jini da kuma samar da zaɓi mai mahimmanci ga marasa lafiya da nau'in ciwon sukari na 2. A fagen kula da kiba, GLP-1 na iya rage yawan kuzarin kuzari ta hanyar dabaru irin su hana ci abinci na tsakiya da jinkirta zubar da ciki, taimakawa masu kiba su rasa nauyi da inganta yanayin rayuwa. Bugu da ƙari, GLP-1 yana nuna yiwuwar aikace-aikace a cikin rigakafi da kuma kula da cututtuka na zuciya da jijiyoyin jini, da kuma inganta yanayin haɗarin cututtukan zuciya yana ba da sabuwar hanya don rage abubuwan da ke faruwa na cututtukan zuciya. Bayyanar GLP-1 ba wai yana wadatar hanyoyin magance cututtukan da ke da alaƙa ba amma kuma yana kawo sabon bege don inganta ingancin rayuwa da lafiyar marasa lafiya.

Game da Marubuci

Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.

Mawallafin Jaridar Kimiyya

Hegner P mai bincike ne a Jami'ar Regensburg. Ayyukansa sun haɗa da Chemistry, Tsarin zuciya, da Ilimin zuciya. A cikin Chemistry, yana bincika halayen da ke da alaƙa da lafiyar zuciya. A cikin nazarin tsarin zuciya na zuciya, yana bincikar zuciya da ayyuka na jirgin ruwa, yana neman fahimtar hanyoyin warkewa. Binciken ilimin zuciyarsa yana mai da hankali kan rigakafin cututtukan zuciya, ganowa, da magani.

Gudunmawar Hegner tana da mahimmanci. Bayanan sinadarai nasa sun haifar da sabon ci gaban magungunan cututtukan zuciya. Ayyukansa akan hanyoyin zuciya da na jirgin ruwa sun inganta fahimtar cututtukan zuciya. A asibiti, bincikensa ya inganta tsarin kula da cututtukan zuciya, yana haɓaka matakan kula da marasa lafiya. Gabaɗaya, tsarin koyarwa da yawa na Hegner yana wadatar da maganin cututtukan zuciya, yana ba da bege don rage nauyin cututtuka da ingantacciyar sakamako mai haƙuri. An jera Hegner P a cikin ambaton ambaton [8].

▎ Abubuwan da suka dace

[1] Memon A, Tehrim M, Kumari B. GLP-1: sabuwar alfijir ga masu ciwon sukari[J]. Jaridar Ƙungiyar Likitocin Pakistan, 2023,73 (3): 721.DOI: 10.47391 / JPMA.7558.

[2] Ma H, Huang W, Wang X, et al. Fahimtar tsari game da kunna GLP-1R ta ƙaramin agonist kwayoyin [J]. Binciken Cell, 2020,30 (12):1140-1142.DOI:10.1038/s41422-020-0384-8.

[3] Kim HS, Jung C H. Oral GLP-1, Glucagon Na Farko Mai Ingestible-Kamar Peptide-1 Mai karɓar Agonist: Zai Iya Zama Harsashin Sihiri don Ciwon sukari Na 2?[J]. Jarida ta Duniya na Kimiyyar Kwayoyin Halitta, 2021,22(18).DOI:10.3390/ijms22189936.

[4] Gabery S, Salinas CG, Paulsen SJ, et al. GLP-1 yana rage nauyin jiki a cikin rodents ta hanyar rarraba hanyoyin jijiyoyi [J]. Jci Insight, 2020,5 (6).DOI:10.1172/jci.inji.133429.

[5] Katsurada K, Yada T. Tasirin jijiyoyi na gut- da kwakwalwa-samu glucagon-kamar peptide-1 da agonist mai karɓa [J]. Jaridar Binciken Ciwon sukari, 2016,7:64-69.DOI:10.1111/jdi.12464.

[6] Ryan DH, Lingvay I, Colhoun HM, et al. GLP-1 Tasiri kan Sakamakon Zuciya a cikin Mutanen da ke da Kiba ko Kiba (SELECT) dalili da ƙira[J]. Jaridar Zuciya ta Amurka, 2020,229:61-69.DOI:10.1016/j.ahj.2020.07.008.

[7] Christou GA, Katsiki N, Blundell J, et al. GLP-1 azaman maganin rigakafin kiba mai alƙawarin [J]. Sharhin Kiba, 2019,20(6):805-815.DOI:10.1111/obr.12839.

[8] Hegner P, Seitz S, Schopka S, et al. GLP-1 yana haɓaka aikin kwangila a cikin keɓewar atrium na ɗan adam[J]. Jaridar Zuciya ta Turai, 2024,45.DOI:10.1093/eurheartj/ehae666.3729.

[9] Knudsen LB, Lau J. Ganowa da Ci gaban Liraglutide da GLP-1[J]. Ƙimar a cikin ilimin endocrinology, 2019,10.DOI:10.3389/fendo.2019.00155.

[10] Ryan DH, Lingvay I, Deanfield J, et al. Sakamakon asarar nauyi na dogon lokaci na GLP-1 a cikin kiba ba tare da ciwon sukari ba a cikin gwajin SELECT [J]. Magungunan yanayi, 2024,30 (7): 2049-2057.DOI: 10.1038/s41591-024-02996-7.

[11] Alanazi M, Alshahrani JA, Aljaberi AS, et al. Tasirin GLP-1 a cikin Mutanen da ke da Kiba ko Kiba Ba tare da Ciwon sukari ba [J]. Jaridar Cureus na Kimiyyar Kiwon Lafiya, 2024,16 (8).DOI:10.7759/cureus.67889.

[12] Ojeniran M, Dube B, Paige A, et al. GLP-1 don asarar nauyi [J]. Likitan Iyali na Kanada, 2021,67 (11): 842.DOI: 10.46747/cfp.6711842.

[13] Papakonstantinou I, Tsioufis K, Katsi V. Haskaka kan Tsarin Aiki na GLP-1[J]. Matsalolin Yanzu A cikin Halittar Halitta, 2024,46(12):14514-14541.DOI:10.3390/cimb46120872.

DUKKANIN LABARI DA BAYANIN KAYAYYA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.  

Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da kowane yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.