GLP-110 mg

▎ Ọdịdị GLP-1

▎ Nchọpụta GLP-1

Kedu ihe ndabere nyocha nke GLP-1?

GLP-1 bụ glucagon-dị ka peptide-1 (GLP-1) analọgụ, nkewa dị ka GLP-1 agonist nnabata. GLP-1 bụ homonụ ebumpụta ụwa nke mkpụrụ ndụ eriri afọ na-ezobere mgbe o richara nri. Ọ na-ekere òkè n'ịkwalite mmepụta insulin na igbochi secretion glucagon, si otú ahụ na-achịkwa ọkwa glucose ọbara. Mmepe nke GLP-1 sitere na nyocha miri emi nke ọrụ physiological nke GLP-1. Otú ọ dị, GLP-1 nwere ọkara ndụ dị mkpụmkpụ dị mkpirikpi n'ime ahụ, na-adịru nanị ihe dị ka nkeji 1 ruo 2, nke a na-ekwu na ọ nwere ike imebi ya site na dipeptidyl peptidase-4 (DPP-4) enzymes n'ime ahụ. Iji merie mmachi a, ndị ọkà mmụta sayensị gbanwere nhazi nke GLP-1 site na nnọchi amino acid dị iche iche na mgbakwunye nke otu nchebe, na-eme ka nguzogide ya na enzymes DPP-4 ma si otú a na-agbatị ogologo oge ọrụ ya ^[1] . Na nhazi nke GLP-1, alanine na 8th na-anọchi anya α-aminoisobutyric acid (Aib). Mgbanwe a abụghị naanị na-eme ka nkwụsi ike nke ọgwụ ahụ dịkwuo mma kamakwa ọ na-ewusi njikọ ya na onye na-anabata GLP-1 (Ma H, 2020). Na mgbakwunye, eriri acid fatty pụrụ iche jikọtara ya na C-terminus, jikọtara site na γ-glutamine na residu lysine, na-agbatịkwu ọkara ndụ, na-eme ka ịgba ọgwụ mgbochi otu ugboro kwa izu ma ọ bụ nchịkwa ọnụ otu ụbọchị ^[1] . Na mbụ dabere na nyocha na mgbanwe nke GLP-1 eke, GLP-1 na-achọ ịnye nhọrọ ọgwụgwọ dị irè maka ndị ọrịa nwere ụdị ọrịa shuga 2 ^{[1, 2]} . Mgbe nkwalite nhazi ya gasịrị, ọ na-ejigide ọrụ physiological nke GLP-1 ebe ọ na-emeziwanye akụrụngwa ọgwụ ya, na-aghọ agonist GLP-1 dị mkpa na-eme ogologo oge. Nnyocha na mmepe nke GLP-1 dị oke mkpa maka ọgwụgwọ ụdị ọrịa shuga 2, na-enye ndị ọrịa nhọrọ ọhụrụ. Site n'ịkwalite usoro ahụ, ọ na-emeri nsogbu nke obere ndụ nke GLP-1 dị mkpụmkpụ, na-eme ka nkwụsi ike nke ọgwụ na ogologo oge na-arụ ọrụ.

Kedu ihe bụ usoro nke GLP-1?

GLP-1 bụ glucagon na-arụ ọrụ ogologo oge dị ka peptide-1 (GLP-1) agonist nnabata, na usoro ya bụ nke a:

Iwu Glucose Ọbara: Dị ka akwụkwọ akụkọ glucagon-dị ka peptide-1 agonist receptor (GLP-1RA), GLP-1 na-ebelata agụụ ndị ọrịa maka nri ma na-ebelata mmasị ha maka nri nwere nnukwu abụba site na igbochi agụụ. Ọ na-ahazi ebe a na-eri nri na hypothalamus, na-ebelata iri nri, na-abawanye satiety, na-egbochi ịwụfu afọ, na ibelata motility eriri afọ, si otú a na-enweta ebumnuche nke ịbelata ibu. Mbelata ibu na-enyere aka melite nguzogide insulin ma na-achịkwa ọkwa glucose ọbara ^[3] (Kim HS, 2021). GLP-1 na-ebute mbelata ibu n'ime òké site n'ụzọ akwara nke kesara ekesa. Nnyocha egosiwo na GLP-1 na-arụ ọrụ ozugbo na mpaghara dịka ụbụrụ ụbụrụ, septal nucleus, na hypothalamus. Ọ bụ ezie na ọ naghị agafe ihe mgbochi ụbụrụ-ọbara, ọ na-emekọrịta ihe na ụbụrụ site na akụkụ okirikiri na mpaghara ụfọdụ dị nso na ventricles. Ọ na-akpalite ịgbalite c-Fos etiti na mpaghara ụbụrụ 10, gụnyere mpaghara azụ azụ nke GLP-1 na mpaghara nke abụọ lekwasịrị anya ozugbo na-enweghị mmekọrịta GLP-1R ozugbo, dị ka akụkụ parabrachial nucleus. Nyocha akpaaka na-egosi na ịgbalite ahụ nwere ike jikọta ya na nkwụsị nke nri ndị neurons na-achịkwa na akụkụ parabrachial nucleus, si otú ahụ na-achịkwa ọkwa glucose ọbara ^[4].

Iwu Gastrointestinal: GLP-1 na-arụ ọrụ na ndị na-anabata GLP-1 na eriri afọ. Site n'ụzọ afferent nke akwara vagus, ọ na-eme na mpaghara ụbụrụ dị ka nucleus nke traktị naanị ya na dorsal moto nucleus nke akwara vagus iji na-achịkwa motility eriri afọ. Ọ nwere ike igbochi mkpụkọ nke antrum gastric, welie esemokwu nke sphincter pyloric, gbatịa oge obibi nri n'ime afọ, na-egbu oge ịbanye na duodenum, na-egbochi ịrị elu ngwa ngwa nke glucose ọbara postprandial na ime ka glucose ọbara gbanwee ka ọ kwụsie ike ^[5] (Katsurada K, 2016). Na mgbakwunye, GLP-1 na-arụ ọrụ na ndị na-anabata GLP-1 na sistemu ụjọ nke etiti, ọkachasị na mpaghara ndị dị ka arcuate nucleus na paraventricular nucleus nke hypothalamus. Ọ na-egbochi ntọhapụ nke ihe na-akpali agụụ mmekọahụ dị ka neuropeptide Y (NPY) na protein metụtara agouti (AgRP), ma n'otu oge ahụ na-arụ ọrụ pro-opiomelanocortin (POMC) neurons, na-akwalite nzuzo nke α-melanocyte-akpali akpali hormone (α-MSH) ^[5] . Mmetụta ndị a na-emepụta mmetụta nke afọ ojuju, belata agụụ, na ibelata oriri nri, na-enwe mmetụta dị mma na njikwa glucose ọbara n'ụzọ na-apụtaghị ìhè.

Nchedo obi obi: GLP-1 nwere ike ịkwalite mkpụrụ ndụ endothelial vaskụla iji hapụ ihe ndị na-akpata vasodilator dị ka nitric oxide (NO), na-eme ka ikike mgbasawanye vaskụla na-eme ka ọ dịkwuo mma. N'otu oge ahụ, ọ na-egbochi nzaghachi mkpali na nrụgide oxidative, na-ebelata mmebi nke sel endothelial vaskụla, ma na-ebelata ohere nke atherosclerosis. Ọzọkwa, site n'ibelata agụụ na iri nri, GLP-1 na-enyere aka na mbelata ibu, na-eme ka ọrịa shuga na-egbu egbu, na-ebelata ọkwa nke triglycerides na obere njupụta lipoprotein cholesterol (LDL-C), ma na-abawanye ọkwa nke cholesterol lipoprotein dị elu (HDL-C). Ọ nwekwara ike inwe mmetụta bara uru na ọbara mgbali elu site n'ịchịkwa hemodynamics renal na ọrụ neuroendocrine, na-ebelata ihe ize ndụ nke ọbara mgbali elu na ihe ize ndụ ọrịa obi ^[6]..

GLP-1 na ụkpụrụ ntụgharị nke WAT na ntụgharị BAT yana ịgbalite BAT.

Isi mmalite: PubMed ^[12]

Gịnị bụ isi nnwale na ọmụmụ?

Nhazi na nkwalite nke Ọdịdị kemịkal: Mgbe ị na-emepụta GLP-1, a nakweere usoro nke ijikọ albumin na-agbanwe agbanwe iji gbasaa ogologo oge nke ọgwụ ahụ. Site n'ịchọpụta ezigbo ngwakọta nke fatty acids na njikọ, ka ị na-ejigide nrụpụta nke onye na-anabata GLP-1 (GLP-1R), a na-abawanye ikike ijikọ na albumin ^[7]..

Ngwa ọgwụ: GLP-1 bụ glucagon-dị ka peptide-1 agonist receptor (GLP-1 RA) nke nwere ogologo oge mkpochapụ ọkara ndụ, na-enye ohere maka ịgba ọgwụ mgbochi subcutaneous otu ugboro kwa izu. N'ime ndị ọrịa nwere ụdị ọrịa shuga 2 (T2DM), mmetụta mbelata arọ nke ịgba ọgwụ subcutaneous nke GLP-1 otu ugboro kwa izu dị elu karịa nke GLP-1RA ndị ọzọ otu ugboro kwa izu. N'ime usoro nyocha nke usoro nke II maka ndị ọrịa buru ibu na-enweghị T2DM, injection subcutaneous nke GLP-1 kwa ụbọchị gosipụtara mmetụta mbelata dị mma karịa placebo na otu ugboro kwa ụbọchị 3.0 mg liraglutide. Ogo ọnwụ nke GLP-1 kpatara n'ọmụmụ ihe a karịrị ụkpụrụ maka ọgwụ na-ebelata ibu nke European Medicines Agency (EMA) na US Food and Drug Administration (FDA) setịpụrụ, ọ dịkwa mma, na-egosi na ntụtụ nke GLP-1 otu ugboro kwa ụbọchị nwere ike ịghọ ọgwụ na-efunahụ ibu n'ọdịnihu ^[8].

Ọgwụgwọ ọrịa obi site na imeziwanye ọrụ obi: Nsonaazụ nke ule STEP-HFpEF gosiri na nnukwu ọgwụ antidiabetic glucagon-like peptide 1 agonist GLP-1 mere ka akara ngosi ndị metụtara nkụda obi nke obi na-eji obere ejection echedoro (HFpEF) ma belata ọkwa N-terminal na-ụdị pro-NTP-BN. Nnwale nyocha achọpụtala na nnukwu ọgwụgwọ na GLP-1 nwere ike ịbawanye esemokwu nke trabeculae mmadụ ihe karịrị ugboro atọ n'ụzọ dabere na dose, na-enweghị mmụba nke arrhythmia. Mmetụta a nwere ike ịbụ n'ihi mmụba nke Ca2+ site na reticulum sarcoplasmic. Ọgwụgwọ GLP-1 dị elu na ndị ọrịa nwere nkụda mmụọ nwere ike melite ọrụ atrial, si otú ahụ na-ebelata mgbaàmà ^[9].

A na-enyocha GLP-1 maka ọgwụgwọ steatohepatitis na-adịghị egbu egbu (NASH): Nhazi ezi uche nke GLP-1 enyela nnukwu onyinye iji meziwanye njikwa glucose ọbara, ịdị arọ ahụ, ọbara mgbali elu, lipids ọbara, ọrụ β-cell, na usoro obi obi na ndị ọrịa nwere ụdị ọrịa shuga 2. Na mgbakwunye, mmepe nke usoro ọnụ nke GLP-1 nwere ike inye uru ọzọ n'ihe gbasara nnabata ọgwụgwọ ndị ọrịa ^[7]..

Kedu ihe dị iche na mmetụta mbelata ibu nke GLP-1 n'etiti ndị mmadụ dị iche iche?

Ndị okenye nwere ọrịa obi ndị dịbu adị, oke ibu ma ọ bụ oke ibu mana enweghị ọrịa shuga: N'ime SELECT nsonaazụ mkpụrụ obi, GLP-1 belatara ihe omume obi ọjọọ dị njọ site na 20% n'ime ndị okenye 17,604 nwere ọrịa obi dị adị, oke ibu ma ọ bụ oke ibu, yana enweghị ọrịa shuga ^[10] (Ryan DH, 2024). N'ime nyocha a akọwapụtara nke ọma, ndị nyocha nyochara nsonaazụ GLP-1 na ịdị arọ ahụ, nsonaazụ anthropometric, nchekwa, na nnabata dị ka isi ihe nrịbama ahụ (BMI) siri dị. Ndị ọrịa na-anata GLP-1 nwetara mbelata ahụ na-aga n'ihu n'ime izu 65, na-adịgide ruo afọ 4. N'ime izu 208, ma e jiri ya tụnyere otu placebo, GLP-1 mere ka mbelata nkezi ibu ahụ (-10.2%), okirikiri úkwù (-7.7 cm), na úkwù na ịdị elu (-6.9%), ebe otu placebo nwere mbelata nke (-1.5%, -1.3 cm, na -1.0%) n'otu n'otu, na ihe niile atụnyere placebo. Mbelata ibu arọ nke ụlọ ọgwụ mere na ma ndị nwoke ma ndị nwanyị, agbụrụ niile, ụdị ahụ, na mpaghara. Ejikọtara GLP-1 na obere ihe ọjọọ dị njọ. Maka ụdị BMI nke ọ bụla (<30, 30 na <35, 35 na <40, na ≥40 kg/m²), ihe omume nke ajọ omume ọjọọ nke GLP-1 (ọnụọgụ nke ihe ndị a na-ahụ kwa afọ 100 mmadụ) dị ala (43.23, 43.54, 51.01.4, na GLP-51.01, na GLP-1. 49.66, 52.73, na 60.85 maka placebo). Ejikọtara GLP-1 na mmụba nkwusioru nke ngwaahịa nnwale ahụ. Ka ngalaba BMI na-ebelata, ọnụego nkwụsị ahụ mụbara. N'ime nnwale SELECT, na izu 208, GLP-1 weputara nnukwu mfu ụlọ ọgwụ yana ndozi na ụkpụrụ anthropometric ma e jiri ya tụnyere placebo, na ọnwụ ahụ dịgidere ruo afọ 4.

Ndị mmadụ n'otu n'otu bụ ndị buru ibu ma ọ bụ buru ibu ma na-enweghị ọrịa shuga: Nyochaa nhazi nyocha nke ọma na nchekwa nke GLP-1 n'ime ndị mmadụ buru ibu ma ọ bụ buru ibu ma na-enweghị ọrịa shuga ^[11] . Nyochaa a chịkọtara nsonaazụ nke ọtụtụ nnwale ụlọ ọgwụ, na-ekwusi ike mmetụta GLP-1 na mbelata ibu, paramita metabolic, na nsonaazụ ahụike n'ozuzu ya. Nsonaazụ gosiri na ejikọtara GLP-1 na oke ibu dị arọ yana mmụba na ihe ngosi ahụike metụtara oke ibu, yana ọ nwere ike bụrụ nhọrọ ọgwụgwọ bara uru maka ndị ọrịa buru ibu.

Ndị ọrịa na-abụghị ndị ọrịa mamịrị (ihe akaebe sitere na ọtụtụ RCTs): N'ime ule 4 a na-achịkwa nke a na-achịkwaghị achịkwa, ndị ọrịa nwere oke ahụ nke 96 ruo 105 n'arọ natara ntụtụ subcutaneous kwa izu nke 2.4 mg nke GLP-1 na ntinye ndụ (ndụmọdụ, nri, na mmega ahụ) maka ọgwụgwọ ọnwụ. Otu ule a na-achịkwa nke a na-achịkwa maka ndị ọrịa na-abụghị ndị ọrịa mamịrị (N = 1961) gosiri na mgbe izu 68 gasịrị, nkezi ibu arọ bụ 15% (15 n'arọ), bụ nke dị iche na 2% (3 n'arọ) na placebo otu. Ọnụ ọgụgụ nke ndị ọrịa nwere oke ibu nke ≥5% bụ 86% ma e jiri ya tụnyere 32% na otu placebo, na ọnụ ọgụgụ dị mkpa iji gwọọ (NNT) = 2; Ọnụ ọgụgụ nke ndị ọrịa nwere oke ibu nke ≥10% bụ 69% ma e jiri ya tụnyere 12% na placebo otu, na NNT = 2. Mbelata ịdị arọ na-agbada n'ihe dị ka izu 60. Ọnụ ọgụgụ nke ihe ndị na-adịghị mma nke eriri afọ (AEs) bụ 74% ma e jiri ya tụnyere 48% na placebo otu, na ọnụ ọgụgụ dị mkpa iji merụọ (NNH) = 3. Ọnụ ọgụgụ nke ndị ọrịa na-akwụsị ọgwụgwọ n'ihi ihe ọjọọ bụ 7% tụnyere 3% na placebo otu, na NNH = 25. N'ihe ọzọ a na-achịkwaghị achịkwa na-achịkwa ndụ 1 n'ime ndụ ndụ 1 N'ime usoro ndụ 1 na-enweghị usoro (N). Otu GLP-1 bụ 16% (17 n'arọ), nke dị iche na 6% (6 n'arọ) na otu placebo. N'ime nyocha nke nyocha nke usoro nyocha maka ndị ọrịa nwere ọrịa shuga (N = 1210), a na-enye ndị ọrịa 2.4 mg nke GLP-1 kwa izu, 1.0 mg nke GLP-1 kwa izu, ma ọ bụ placebo. Mgbe izu 68 gachara, nkezi oke mfu bụ 10% (2.4 mg), 7% (1.0 mg), na 3% (placebo) n'otu n'otu. Ọnụ ọgụgụ nke ndị ọrịa nwere oke ibu nke ≥5% bụ 69% (2.4 mg), 57% (1.0 mg) ma e jiri ya tụnyere 29% na otu placebo. Maka 2.4 mg na 1.0 mg doses, NNT = 9. Ihe ọjọọ ndị ahụ yiri n'etiti usoro dị iche iche. N'ime usoro nlekọta ahụike na-achịkwa nke ọma (N = 803), ndị na-abụghị ndị ọrịa mamịrị na-anata ọgwụgwọ kwa izu na 2.4 mg nke GLP-1 maka izu 20, wee kewaa ya n'otu n'otu na-aga n'ihu na ọgwụgwọ GLP-1 ma ọ bụ otu placebo. Mgbe izu 48 gachara, otu ahụ na-aga n'ihu na ọgwụgwọ GLP-1 tụfuru 8% nke ahụ ha, ebe placebo otu nwetara 7% nke ahụ ha.

N'ikpeazụ, GLP-1 bụ GLP-1 agonist agonist nke nwere uru ngwa n'ọtụtụ mpaghara. N'ihe gbasara ọgwụgwọ ọrịa shuga, ọ na-achịkwa ọkwa glucose ọbara nke ọma site na ijikọ ndị na-anabata GLP-1, na-akwalite mmepụta insulin, na igbochi mwepụta glucagon, na-enye nhọrọ ọgwụgwọ dị mkpa maka ndị ọrịa nwere ụdị ọrịa shuga 2. N'akụkụ ọgwụgwọ oke ibu, GLP-1 na-ebelata ike oriri site na usoro dị ka mbelata agụụ nke etiti na igbu oge na-egbu oge, na-enyere ndị ọrịa buru ibu aka ifelata ma melite ọkwa ha. Na mgbakwunye, GLP-1 na-egosikwa atụmanya ngwa nwere ike na mgbochi na ọgwụgwọ ọrịa obi. Ọganihu ya nke ihe ize ndụ nke obi na-enye ụzọ ọhụrụ iji belata ihe omume nke obi.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Hegner P bụ onye nyocha na Mahadum Regensburg. Ọrụ ya gụnyere Chemistry, Cardiovascular System, na Cardiology. Na Chemistry, ọ na-enyocha mmeghachi omume jikọtara na ahụike obi. N'ime usoro ọmụmụ Cardiovascular, ọ na-enyocha obi na ọrụ arịa, na-achọ nghọta ọgwụgwọ. Nnyocha nke Cardiology ya na-elekwasị anya na mgbochi ọrịa obi, nchọpụta, na ọgwụgwọ.

Enyemaka Hegner dị oke mkpa. Nghọta kemịkalụ ya akwalitela mmepe ọgwụ obi ọhụrụ. Ọrụ ya na usoro obi na arịa emewo ka nghọta nke ọrịa obi. Na ụlọ ọgwụ, nchọpụta ya emeela ka nlekọta ọrịa obi dịkwuo mma, na-ebuli ụkpụrụ nlekọta ndị ọrịa. N'ozuzu, ụzọ dị iche iche nke Hegner na-eme ka nkà mmụta ọgwụ na-eme ka obi dịkwuo mma, na-enye olileanya maka mbelata ibu ọrịa na nsonaazụ ndị ọrịa ka mma. Edepụtara Hegner P na ntụaka nke ntụaka ^[9].

▎ Okwu ndị dị mkpa

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[2] Ma H, Huang W, Wang X, et al. Nghọta ihe arụrụ arụ na ịgbalite GLP-1R site na obere agonist molecule[J]. Nnyocha cell, 2020,30 (12): 1140-1142.DOI:10.1038/s41422-020-0384-8.

[3] Kim HS, Jung C H. Oral GLP-1, Glucagon nke mbụ ingestible-dị ka Peptide-1 Nnabata Agonist: Ọ nwere ike ịbụ ihe anwansi maka ụdị ọrịa shuga 2?[J]. Akwụkwọ akụkọ International nke Science Molecular, 2021,22(18).DOI:10.3390/ijms22189936.

[4] Gabery S, Salinas CG, Paulsen SJ, et al. GLP-1 na-ebelata ibu ahụ n'ime òké site na ụzọ akwara kesaara [J]. Jci Insight, 2020,5 (6).DOI:10.1172/jci.insight.133429.

[5] Katsurada K, Yada T. Mmetụta akwara nke gut- na ụbụrụ sitere na glucagon-dị ka peptide-1 na onye na-anabata ya [J]. Akwụkwọ akụkọ nyocha ọrịa shuga, 2016,7: 64-69.DOI: 10.1111 / jdi.12464.

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Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.  

Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadobeghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.