Tirzepatid (GLP-2) 45 mg

▎ Ọdịdị GLP-2

▎ Nchọpụta GLP-2

Kedu ihe ndabere nyocha nke GLP-2?

GLP-2 bụ ọgwụ polypeptide sịntetik, mmepe ya sitere na nghọta miri emi nke oke nke GLP-1 agonists nnabata dị na ọgwụgwọ ụdị 2 metabolism na oke ibu. Ọ bụ ezie na ndị na-anabata GLP-1 egosilarị arụmọrụ dị mma na njikwa glucose ọbara na mbelata ibu arọ, ndị ọkà mmụta sayensị achọpụtala na ka ha na-arụ ọrụ GLP-1 receptor, mmetụta ha na-arụ ọrụ na onye na-anabata GIP adịghị ike, nke ruo n'ókè ụfọdụ na-egbochi mmetụta ọgwụgwọ ọgwụ. Ya mere, otu nyocha na mmepe na-agba mbọ imepụta ụdị ọgwụ ọhụrụ nke nwere ike ịgbalite ma GIPR na GLP-1R n'otu oge, na-atụ anya inweta njikwa glucose ọbara zuru oke ma dị irè na njikwa ibu ^[1]. .

N'ime usoro nyocha na mmepe nke GLP-2, ndị ọkà mmụta sayensị emeela ọtụtụ nyocha nke isi na nnwale ụlọ ọgwụ. Nke mbụ, n'ime usoro nyocha nke izizi, a tụlere njirimara ọgwụ GLP-2 nke ọma site na nnwale anụmanụ, na ikike ọ nwere na njikwa glucose ọbara na mbelata ịdị arọ ka enwetara. Nsonaazụ gosiri na GLP-2 nwere ike ibelata ọkwa glucose ọbara n'ụdị anụmanụ ma rụọ ọrụ nke ọma na njikwa ibu. Nchọpụta ndị a dị mma tọrọ ntọala siri ike maka ule ụlọ ọgwụ na-esote.

Mgbe nke ahụ gasịrị, GLP-2 banyere n'ọkwa nnwale ụlọ ọgwụ, gụnyere ule nke I, II, na III. N'ime oge ikpe nke mbụ, a na-enyocha nchekwa, nnabata, na njirimara ọgwụ ọgwụ, yana nsonaazụ gosipụtara na GLP-2 nwere ezigbo nchekwa na nnabata. Nnwale nke usoro nke abụọ nyochara ịdị irè na nchekwa nke usoro GLP-2 dị iche iche na ndị ọrịa nwere ụdị 2 metabolism, ma buru ụzọ kpebie oke dose ya dị mma. Ọnwụnwa ụlọ ọgwụ kachasị mkpa nke III, dị ka usoro ọmụmụ SURPASS, kpuchiri ọnụ ọgụgụ buru ibu nke ndị ọrịa nwere ụdị ọrịa shuga 2. Nsonaazụ gosiri na GLP-2 dị nnọọ elu karịa ndị agonists GLP-1 dị adị, dị ka GLP-1, n'ibelata glucose na ibu ọbara. Nsonaazụ nsonaazụ a nyere nkwado nkwado siri ike maka ngwa ahịa nke GLP-2 ^[1].

GLP-2 bụ polypeptide mejupụtara amino asịd 39, nke emezigharịrị n'ụdị amino asịd nke ọ bụla iji kwalite nkwụsi ike na arụmọrụ ya. Nhazi nhazi a pụrụ iche na-enyere GLP-2 aka ijikọ mmetụta nke homonụ incretin abụọ, GIP na GLP-1, n'ime otu molekul, ma mee ka ndị na-anabata homonụ na-etinye aka na njikwa glucose ọbara site na usoro omume abụọ. Kpọmkwem, GLP-2 nwere ike ime ma pancreas na sistemu ụjọ nke etiti. N'otu aka ahụ, ọ na-akwalite mmepụta insulin ma na-egbochi mwepụta glucagon, si otú a na-ebelata glucose ọbara n'ụzọ dị irè; N'aka nke ọzọ, site n'igbu oge nkwụsị nke gastric na ịba ụba satiety, ọ na-ebelata agụụ na iri nri, ma si otú a na-enweta njikwa ibu. Usoro ihe omume abụọ a na-enye GLP-2 uru pụrụ iche na ọgwụgwọ ụdị 2 metabolism na oke ibu, na-enye ndị ọrịa nhọrọ ọgwụgwọ zuru oke ^..

Kedu ihe bụ usoro nke GLP-2?

GLP-2 na-ebelata glucose ọbara site na ọtụtụ usoro na-arụkọ ọrụ ọnụ, dị ka ndị a: ịgbalite onye na-anabata GLP-1: GLP-2 na-ejikọ ya na onye na-anabata GLP-1 na mkpụrụ ndụ beta pancreatic, na-eṅomi mmetụta nke GLP-1 eke. GLP-1 bụ homonụ nke emepụtara n'ime eriri afọ ma dị oke mkpa maka idowe glucose homeostasis 2. Ọ nwere ike ịkwalite njikọ insulin, mmepụta insulin, na mmetụta glucose, ma belata secretion glucagon iji kwalite satiety na igbochi agụụ 2.

Nrụ ọrụ a nwere ike ịkwalite mmepụta insulin. Insulin bụ isi homonụ na-ebelata glucose n'ọbara n'ime ahụ, nke nwere ike ịbawanye nnabata na ojiji nke glucose site na sel, si otú ahụ belata ọkwa glucose ọbara. N'ime ndị ọrịa nwere ụdị ọrịa metabolism nke 2, insulin ezughị oke ma ọ bụ na-ebelata mmetụta nke mkpụrụ ndụ na insulin, na-eduga n'ịbawanye glucose ọbara. GLP-2 na-abawanye mmepụta insulin site na ịgbalite GLP-1 nnabata, nke na-enyere aka melite njikwa glucose ọbara. N'otu oge ahụ, ịgbalite GLP-1 nnabata nwekwara ike igbochi ntọhapụ nke glucagon. Glucagon na-akwalitekarị glycogenolysis na gluconeogenesis na steeti ibu ọnụ, na-abawanye mmepụta glucose ọbara. Site na igbochi mmetụta glucagon, GLP-2 na-ebelata isi iyi nke glucose ọbara, nke na-enyere aka ịchịkwa glucose ọbara ^[2] (Anonymous, 2023).

Ntinye nke onye nnabata GIP: GLP-2 na-eme ihe na onye nnabata GIP n'otu oge. Mgbe arụ ọrụ ya gasịrị, ọ nwere ike ịkwalite mmetụta insulin na nzuzo. Onye na-anabata GIP na-anọkarị na anụ ahụ dịka mkpụrụ ndụ beta pancreatic. Mgbe ịgbalitechara ya, site na njikwa nke ụzọ mgbaàmà intracellular, secretion insulin na-abawanye, na nzaghachi nke mkpụrụ ndụ na insulin na-eme ka ọ dịkwuo mma, si otú a na-ebelata glucose ọbara n'ụzọ dị irè karị 2. GLP-2 bụ nke mbụ na klas dual glucagon-dị ka peptide-1 na glucose-adabere na glucose na-adabere na insulinotropic polypeptide (GIP) analogues nke ndị okenye na-akwado ụdị ọgwụgwọ insulin na-edozi ahụ. 2. GLP-2 bụ usoro kemịkalụ sịntetik dabere na usoro GIP, nke nwere peptide 39-amino acid mejupụtara. Ọ na-abawanye mmepụta insulin, na-ebelata ntọhapụ nke glucagon n'ụzọ dabere na glucose, na-ebelata ọnụ ọgụgụ glucose ọbara na-ebu ọnụ na postprandial, na-akwalite satiety, na-ebelata ibu, na-egbu oge ịpụpụ afọ.

Mmetụta agonist onye na-anabata ihe abụọ a na-eme GLP-2 dị irè karị n'ịkwalite mmepụta insulin na igbochi ntọhapụ glucagon karịa otu GLP-1 agonists ^[2]..

Na-egbu oge mkpofu gastric na ịba ụba satiety: GLP-2 nwere ike igbu oge ịwụfu afọ, gbatịa oge obibi nri n'ime afọ, na-ebelata ogo nnabata nke nri, wee zere mmụba dị ukwuu na glucose ọbara mgbe nri gasịrị. N'ihe ọmụmụ izizi na nke ụlọ ọgwụ, mmetụta GLP-2 na mkpofu afọ dị ka nke GLP-1 agonists. N'ime oke oke oke nri kpatara nri, ogo nke igbu oge afọ nke GLP-2 yiri nke GLP-1, mana mmetụta mgbochi ndị a na-apụ n'anya mgbe izu abụọ gachara ọgwụgwọ. N'ime ndị na-eso ya nwere ma na-enweghị ụdị 2 metabolism, GLP-2 otu ugboro kwa izu (≥5 na ≥4.5mg, n'otu n'otu) na-egbu oge mkpochapụ afọ mgbe otu ọgwụ gasịrị. N'ime ndị sonyere ahụike, a na-ebelata mmetụta a mgbe ọtụtụ doses nke GLP-2 ma ọ bụ dulaglutide ^{[3] gasịrị.} .

N'otu oge ahụ, ọ pụkwara ime ihe na usoro nhụjuanya nke etiti, na-abawanye satiety, na ibelata agụụ na nri oriri. Site n'ịchịkwa oriri, ọ na-enyere aka ịchịkwa ọkwa glucose ọbara n'ụzọ na-apụtaghị ìhè, karịsịa maka nsogbu oke ibu nke ndị ọrịa nwere ụdị 2 metabolism na-esonyere ya, ma na-enyere aka melite nguzogide insulin na ọnọdụ metabolic zuru oke ^[2]..

Imeziwanye mmetụta insulin na metabolism lipid: achọpụtara GLP-2 na-abawanye ọkwa adiponectin, nke bụ adipocytokine metụtara mmetụta insulin. Mmụba nke adiponectin na-enyere aka imeziwanye uche insulin, na-eme ka mkpụrụ ndụ na-enwe mmetụta nke insulin, wee si otú a na-ewelite ma jiri glucose mee ihe nke ọma, na-ebelata glucose ọbara ^[2]..

Na mgbakwunye, GLP-2 nwekwara ike melite profaịlụ lipid ma nwee mmetụta nchebe na ahụike obi. E gosiputara GLP-2 nwere ike imeziwanye ọbara mgbali elu, belata obere njupụta lipoprotein (LDL) cholesterol na triglycerides ^[4] .Nke a na-akwado uru ya zuru oke na njikwa glucose ọbara.

Nnyocha metụtara ya

Ịdị irè na njikwa ibu na ndị ọrịa nwere oke ibu na ụdị 2 metabolism: 

Ọtụtụ ọmụmụ ụlọ ọgwụ ekwenyela na mmetụta mbelata ibu dị ukwuu: N'ime nyocha nke aha ya bụ 'SURMOUNT-2', nnwale a bụ usoro nke 3, kpuru ìsì abụọ, nke enweghị usoro, ebe a na-achịkwa placebo na mba asaa. Ndị okenye (ndị dị afọ ≥18) nwere ọnụọgụ anụ ahụ (BMI) nke 27 kg / m² ma ọ bụ karịa na hemoglobin glycated (HbA₁c) nke 7-10% ka ekenye ya n'enweghị usoro ka ọ nata ntụtụ n'okpurucutaneous otu ugboro kwa izu nke GLP-2 (10mg ma ọ bụ 15mg) ma ọ bụ placebo maka izu 72. Nsonaazụ gosiri na n'izu 72, pasent nke ibu ibu na GLP-2 10mg na 15mg otu bụ -12.8% na -14.7%, n'otu n'otu, ebe na placebo otu bụ -3.2%. Atụmatụ ọgwụgwọ dị iche iche nke GLP-2 10mg na 15mg ma e jiri ya tụnyere placebo bụ -9.6 pasent na -11.6 pasent, n'otu n'otu, ha abụọ dị ịrịba ama ọnụ ọgụgụ (p＜0.0001). Na mgbakwunye, ọtụtụ ndị ọrịa a na-emeso GLP-2 ruru n'ọnụ ụzọ mfu nke 5% ma ọ bụ karịa (79 - 83% vs 32%) ^[5] (Garvey WT, 2023). N'ime ọmụmụ 'SURMOUNT-2', nkezi ịdị arọ nke ntọala bụ 100.7 kg, BMI bụ 36.1 kg/m², na HbA₁c bụ 8.02%. Mgbe izu iri asaa na abụọ nke ọgwụgwọ gasịrị, GLP-2 abụghị naanị ibelata ibu ibu mana ọ rụkwara ọrụ dị mma na njikwa glucose ọbara ^[5]..

Mmetụta dị mma na neuropathy metụtara metabolism: 

Ụfọdụ nnyocha egosiwo na glucagon-dị ka peptide 1 agonists (GLP1-RAs) nwere ike ibelata ihe ize ndụ nke ịda mbà n'obi na ndị ọrịa nwere ụdị 2 metabolism site na imeziwanye ebe nchekwa, mmụta, na imeri adịghị ike nghọta. Dị ka onye na-anabata insulin polypeptide receptor agonist abụọ (GIP-RA) / GLP-1RA, a mụrụ GLP-2 maka mmetụta ya na nrịbama nke uto neuronal (CREB na BDNF), apoptosis (BAX / Bcl2 ratio), ọdịiche (pAkt, MAP2, GAP43, na AGBL4), na nguzogide insulin (GLUT1, GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1, GLUT1, GLUT1 na GLUT1, GLUT1). Neuroblastoma cell line (SHSY5Y). Nsonaazụ nke oge mbụ kwusiri ike ọrụ GLP-2 n'ịgbalite ụzọ pAkt/CREB/BDNF na mgbago mgbago mgbago ala, yana ịdị irè ya na neuroprotection. O gosikwara na GLP-2 nwere ike igbochi mmetụta ndị metụtara hyperglycemia na nguzogide insulin na ọkwa neuronal. Ya mere, GLP-2 nwere ike imeziwanye neurodegeneration nke hyperglycemia kpatara wee merie nguzogide insulin nke neuronal, na-enye nghọta ọhụrụ maka mmelite nke neuropathy metụtara metabolism ^[6]. .

Ọganihu nyocha na ọgwụgwọ ụdị 2 metabolism: 

Ụfọdụ ọmụmụ egosila na GLP-2, dị ka ụdị ọgwụ hypoglycemic ọhụrụ, aghọwo onye mbụ GIP/GLP-1R agonist kwadoro maka ọgwụgwọ nke metabolism na United States. Ekwuputala ya na ọ nwere mmetụta dị ukwuu na-ebelata ọkwa glucose ọbara na oke ibu n'ọtụtụ nnukwu ule ụlọ ọgwụ, yana ihe akaebe na-egosi na ọ nwekwara ikike dị ukwuu na nchebe obi. Na mgbakwunye, echiche nke peptides sịntetik emeghela ọtụtụ ohere amabeghị maka GLP-2. Nnwale na-aga n'ihu (NCT04166773) na ihe akaebe na-egosi na ọ dị ka ọ bụ ọgwụ na-ekwe nkwa n'ọhịa nke ọrịa imeju na-adịghị egbu egbu (NAFLD), renal na neuroprotection, wdg ^[7]..

Mmetụta ogologo oge nke T irzepatide na ahụike obi: 

GLP-2 nwere ike ibelata ihe ize ndụ nke ọrịa obi site n'ịkwalite mbelata ibu. Otu nnyocha nyochara mmetụta nke GLP-2 na oke ibu na ọrịa obi na ọrịa obi na ndị okenye America ^[8] . Nnyocha ahụ chọpụtara na n'etiti ndị okenye America tozuru oke maka ọgwụgwọ GLP-2, mgbe ọgwụgwọ ya na 15mg nke GLP-2, e mere atụmatụ na 70.6% na 56.7% nke ndị okenye nwere mbelata nke ≥15% na ≥20% nke ndị mmadụ, nke pụtara na ọnụ ọgụgụ ndị mmadụ na-ebelata. 58.8% N'ime ndị mmadụ na-enweghị ọrịa obi, ihe ize ndụ nke afọ 10 nke ọrịa obi na-ebelata site na 10.1% tupu ọgwụgwọ ruo 7.7% mgbe ọgwụgwọ gasịrị, na-egosipụta mbelata ihe ize ndụ zuru oke nke 2.4% na mbelata ihe ize ndụ nke 23.6%, nke pụtara na 2 nde ọrịa ọrịa obi nwere ike igbochi n'ime afọ 10.

Na mmechi, GLP-2 bụ akwụkwọ akụkọ dual agonist nke GIP na GLP-1 ndị na-anabata ya ma dị oke mkpa na ọgwụgwọ ụdị 2 metabolism na oke ibu. Ọ nwere ike na-akwalite mmepụta insulin nke ọma, na-egbochi secretion glucagon, na-ahazi glucose ọbara nke ọma, belata ihe ize ndụ nke nsogbu, melite ọrụ nke mkpụrụ ndụ beta pancreatic, na-egbu oge na-aga n'ihu nke metabolism. Ọ nwekwara mmetụta nchebe na usoro obi. N'ịgwọ oke ibu, ọ nwere ike ibelata oriri oriri nke ọma, ibelata agụụ, ịbawanye afọ ojuju, nyere ndị ọrịa buru ibu aka ifelata, ma belata ihe ize ndụ nke nsogbu ndị metụtara oke ibu. Ọ nwekwara ike melite nguzogide insulin na metabolism lipid. Tụkwasị na nke ahụ, ọ na-egosi ike na ọgwụgwọ nke ọrịa ndị metụtara metabolic abnormality dị ka steatohepatitis na-adịghị egbu egbu, ọrịa apnea na-ehi ụra, na nkụda obi, ma nwee ike imeziwanye ọtụtụ ihe ngosi metabolic n'otu oge, na-enye atụmatụ ọgwụgwọ zuru oke. Usoro nchịkwa injection ya kwa izu dị mma maka iji yana nwee ike melite nnabata ọgwụgwọ ndị ọrịa. Site n'ịchịkwa glucose na ịdị arọ nke ọbara nke ọma na ibelata ihe ize ndụ nke nsogbu, ọnọdụ anụ ahụ nke ndị ọrịa nwere ike ime ka ọ dịkwuo mma, ikike ime ihe ha na-eme kwa ụbọchị na ndụ ndụ ha nwere ike ịbawanyewanye, ntụkwasị obi ha nwere na njikwa ọrịa nwere ike ịba ụba, enwere ike belata ibu nke uche ha, na ime mgbanwe mmekọrịta mmadụ na ibe ya nwere ike ime ka ọ dịkwuo mma.

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

Dr. William T. Garvey bụ ọkà mmụta ama ama na onye nyocha jikọtara ya na ọtụtụ ụlọ ọrụ ama ama, gụnyere Mahadum Alabama na Birmingham, Mahadum Aston, na Birmingham Veterans Affairs Medical Center. Nzụlite agụmakwụkwọ ya na ahụmịhe ọkachamara gbasara ọtụtụ ọzụzụ n'ime ngalaba ahụike na sayensị. Dr. Garvey enyela nnukwu onyinye na ngalaba nke endocrinology na metabolism, nutrition and dietetics, biochemistry and molecular bayoloji, yana ọgwụ izugbe na nke ime, na-elekwasị anya na usoro obi na obi. Aghọtala ọrụ ya n'ọtụtụ ebe ma kwanyere ya ùgwù, nke akpọrọ aha ya bụ onye nyocha nke ukwuu na ngalaba Cross-Field maka 2023 na 2024, na-egosipụta mmetụta dị ukwuu na mmetụta nke nyocha ya na mpaghara sayensị sara mbara.

Mmasị nyocha na nka Dr. Garvey gbatịrị akụkụ dị iche iche nke ọrịa metabolic na njikwa ha. Ọ na-arụsi ọrụ ike n'ịmụ banyere metabolism metabolism, oke ibu, na nsogbu ndị metụtara ya, na-achọ ikpughe usoro ọgwụgwọ ọhụrụ yana melite nsonaazụ onye ọrịa. Ọrụ ya gụnyere nchọpụta sayensị bụ isi, nnwale ụlọ ọgwụ, na ọmụmụ ntụgharị, na-ejikọta ọdịiche dị n'etiti nchọpụta ụlọ nyocha na ngwa ahụike ụwa n'ezie. Site na nyocha ya buru ibu, Dr. Garvey enyela aka na nghọta miri emi nke usoro ndị na-akpata ọrịa metabolic ma nyere aka n'ịkpụzi ntuziaka ụlọ ọgwụ na usoro ọgwụgwọ na ngalaba nke endocrinology na metabolism. Dọkịta William T. Garvey ka edepụtara n'akwụkwọ ntụaka ^[5].

▎ Okwu ndị dị mkpa

[1] Nowak M, Nowak W, Grzeszczak W. GLP-2 - GIP/GLP-1 abụọ agonist receptor - ọgwụ antidiabetic ọhụrụ nwere ike ịrụ ọrụ metabolic na ọgwụgwọ ụdị 2 metabolism[J]. Endokrynologia Polska, 2022,73 (4): 745-755.DOI: 10.5603/EP.a2022.0029.

[2] Amaghị aha. GLP-2: A Dual Glucose-dabere na Insulinotropic Polypeptide na Glucagon-dị ka Peptide-1 Agonist maka njikwa nke ụdị 2 ọrịa shuga mellitus: Erratum.[J]. Akwụkwọ akụkọ American Therapeutics, 2023,30 (3): e311.DOI: 10.1097/MJT.000000000001634.

[3] Urva S, Coskun T, Loghin C, et al. Akwụkwọ akụkọ dual glucose-based insulinotropic polypeptide na glucagon-dị ka peptide-1 (GLP-1) agonist receptor GLP-2 na-egbu oge ịpụpụ gastric n'otu aka ahụ na nhọrọ GLP-1 na-anabata agonists [J]. Oke ọrịa shuga na ọrịa shuga, 2020,22(10):1886-1891.DOI:10.1111/dom.14110.

[4] Forzano I, Varzideh F, Avisato R, et al. GLP-2: Mmelite usoro[J]. Akwụkwọ akụkọ International nke Science Molecular, 2022,23 (23).DOI:10.3390/ijms232314631.

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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.