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▎ Ọdịdị Tirzepatid
Isi mmalite: PubChem |
Usoro: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diacid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Ụdị mkpụrụ ndụ: C 225H 348N 48O68 Ibu ibu: 4813 g/mol Nọmba CAS: 2023788-19-2 PubChem CID: 163285897 Ụdị okwu: Zepbound; Mounjaro |
▎ Nyocha Tirzepatid
Gịnị bụ ndabere nyocha nke Tirzepatid?
Tirzepatid bụ ọgwụ polypeptide sịntetik. Nchoputa ya na mmepe ya sitere na nghota miri emi nke oke nke agonists nnabata GLP-1 di na ọgwụgwọ nke 2 metabolism na oke ibu n'oge ahu. Ọ bụ ezie na ndị na-anabata GLP-1 egosila ezigbo arụmọrụ na njikwa glucose ọbara na mbelata ibu, ndị ọkà mmụta sayensị chọpụtara na ịgbalite onye na-anabata GIP adịghị ike, nke na-egbochi ịdị irè nke ọgwụ ahụ ruo n'ókè ụfọdụ. Ya mere, ndị otu nyocha na mmepe gbalịsiri ike imepụta ọgwụ ọhụrụ nke nwere ike ịgbalite ma GIPR na GLP-1R n'otu oge iji nweta njikwa glucose ọbara zuru oke ma dị irè na njikwa ibu [1]..
N'oge usoro nyocha na mmepe nke Tirzepatid, ndị ọkà mmụta sayensị mere ọtụtụ nyocha nyocha na nyocha ụlọ ọgwụ. N'ime usoro nyocha nke izizi, a na-eji nnwale anụmanụ iji nyochaa nke ọma akụrụngwa ọgwụ nke Tirzepatid. Nsonaazụ ahụ gosipụtara ikike ya na njikwa glucose ọbara na mbelata ibu, na-atọ ntọala maka nnwale ụlọ ọgwụ na-esote. Mgbe nke ahụ gasịrị, Tirzepatid batara n'ọkwa nnwale ụlọ ọgwụ, gụnyere nkeji I, II, na III. Usoro nke m tụlere nchekwa, nnabata, na akụrụngwa ọgwụ ọgwụ, nsonaazụ ya gosipụtara ezigbo nchekwa na nnabata. Usoro nke Abụọ nyochara ịdị irè na nchekwa nke usoro ọgwụgwọ dị iche iche na ndị ọrịa nwere ụdị metabolism nke 2, na-ebu ụzọ chọpụta oke dose dị mma. Nnwale ule ụlọ ọgwụ nke isi nke III, dị ka usoro ọmụmụ SURPASS, gụnyere ọnụ ọgụgụ buru ibu nke ndị ọrịa nwere ụdị 2 metabolism. Nsonaazụ gosiri na Tirzepatid dị nnọọ elu karịa ndị na-anabata GLP-1 dị ugbu a, dị ka Semaglutid, na ibelata glucose ọbara na ịdị arọ, na-enye ihe akaebe siri ike maka ngwa ahịa [1].
Tirzepatid bụ polypeptide nke nwere amino acid 39 mejupụtara, na agbanweela nhazi ya iji kwalite nkwụsi ike ya na ọgwụ ọgwụ. Nhazi ya pụrụ iche na-enyere ya aka ijikọ mmetụta nke incretins abụọ, GIP na GLP-1, n'ime otu molekul, na-eme ka ndị na-anabata homonụ na-etinye aka na njikwa glucose ọbara site na usoro abụọ. Kpọmkwem, n'otu aka ahụ, ọ na-arụ ọrụ na pancreas iji kwalite mmepụta insulin ma gbochie mwepụta glucagon iji wedata glucose ọbara; N'aka nke ọzọ, ọ na-arụ ọrụ na usoro nhụjuanya nke etiti, na-egbu oge nkwụsị nke gastric, ịba ụba nke satiety, ibelata agụụ na iri nri, na ịnweta njikwa ibu. Usoro abụọ a na-enye Tirzepatid uru pụrụ iche na ọgwụgwọ ụdị 2 metabolism na oke ibu, na-enye ndị ọrịa nhọrọ ọgwụgwọ zuru oke [1].
Kedu ihe bụ usoro nke Tirzepatid?
Tirzepatid na-ebelata glucose ọbara site na ọtụtụ usoro ndị a:
Nrụ ọrụ nke ndị na-anabata GLP-1: Tirzepatid na-ejikọ ndị na-anabata GLP-1 na mkpụrụ ndụ beta pancreatic, na-eṅomi omume nke GLP-1 eke. GLP-1 bụ homonụ nke eriri afọ na-emepụta nke dị mkpa maka idowe glucose homeostasis. Ọ nwere ike ịkwalite njikọ insulin, nzuzo, na nghọta glucose, yana ibelata secretion glucagon iji kwalite satiety na igbochi agụụ. N'ime ndị ọrịa nwere ụdị metabolism nke 2, ụkọ insulin ezughi oke ma ọ bụ mbelata mmetụta cellular na insulin na-eduga n'ịbawanye glucose ọbara. Tirzepatid na-abawanye mmepụta insulin site na ịgbalite ndị na-anabata GLP-1, na-eme ka njikwa glucose ọbara dịkwuo mma. N'otu oge ahụ, ịgbalite ndị na-anabata GLP-1 nwekwara ike igbochi ntọhapụ nke glucagon, na-ebelata isi mmalite nke glucose ọbara ma na-enye aka na njikwa glucose ọbara [2]..
Nrụ ọrụ nke ndị na-anabata GIP: Tirzepatid na-arụ ọrụ na ndị na-anabata GIP, yana ịgbalite ya nwere ike ịkwalite mmetụta insulin na nzuzo. Ndị na-anabata GIP na-anọkarị na anụ ahụ dịka mkpụrụ ndụ beta nke pancreatic. Mgbe emechara ya, site na ntugharị ụzọ mgbaama intracellular, mmepụta insulin na-abawanye, yana nnabata cell na-anabata insulin, na-ebelata glucose ọbara nke ọma [2] . Mmetụta agonist onye na-anabata ihe abụọ a na-eme Tirzepatid dị irè karịa otu GLP-1 agonists na-anabata ya n'ịkwalite mmepụta insulin na igbochi ntọhapụ glucagon [2]..
Na-egbu oge mkpofu nke afọ na ịba ụba satiety: Tirzepatid nwere ike igbu oge ịwụfu gastric, ịgbatị oge obibi nri n'ime afọ, na-ebelata ọnụego nnabata nke nri, na igbochi mmụba dị ukwuu na glucose ọbara postprandial. Mmetụta ya na mkpofu afọ dị ka nke GLP-1 agonists nnabata. N'otu oge ahụ, ọ na-arụ ọrụ na sistemụ ụjọ nke etiti, na-abawanye satiety, na-ebelata agụụ na iri nri, nke dabara adaba maka nsogbu oke ibu nke ndị ọrịa nwere ụdị 2 metabolism na-esonyere, na-enyere aka melite nguzogide insulin na ọnọdụ metabolic zuru oke [2]..
Imeziwanye mmetụta insulin na metabolism lipid: Tirzepatid nwere ike ịbawanye ọkwa nke adiponectin, adipocytokine metụtara mmetụta insulin, na-enyere aka imeziwanye mmetụta insulin, na-eme ka mkpụrụ ndụ nwee ike ịnara nke ọma na iji glucose, na ibelata glucose ọbara (Anonymous, 2023). Na mgbakwunye, ọ nwekwara ike melite profaịlụ lipid, na-enwe mmetụta nchebe na ahụike obi. E gosiputara na ọ nwere ike ịkwalite ọbara mgbali elu, belata LDL cholesterol na triglycerides [3].
Isi mmalite: PubMed [5]
Kedu ihe ọmụmụ ndị metụtara ya?
Ịdị irè na njikwa arọ na ndị ọrịa nwere oke ibu na ụdị 2 metabolism
Ọtụtụ ọmụmụ ụlọ ọgwụ ekwenyela na Tirzepatid nwere mmetụta dị oke ibu na-efunahụ. N'ime ọmụmụ 'SURMOUNT-2', a na-eme usoro nke 3 a, kpuru ìsì abụọ, enweghị usoro, na-achịkwa placebo na mba asaa. Ndị okenye (afọ ≥ 18) nwere BMI nke 27 kg / m² ma ọ bụ karịa na HbA₁c nke 7-10% debanyere aha wee kenye ya n'enweghị usoro ka ọ nata injection subcutaneous nke Tirzepatid otu ugboro kwa izu (10 mg ma ọ bụ 15 mg) ma ọ bụ placebo maka izu 72. Nsonaazụ gosiri na n'izu 72, pasent nke ibu ibu na Tirzepatid 10 mg na 15 mg otu bụ -12.8% na -14.7% n'otu n'otu, ma e jiri ya tụnyere -3.2% na placebo otu. Atụmatụ ọgwụgwọ dị iche iche nke Tirzepatid 10 mg na 15 mg ma e jiri ya tụnyere placebo bụ -9.6 pasent na -11.6 pasent n'otu n'otu, bụ nke dị ịrịba ama (p <0.0001). Na mgbakwunye, ọtụtụ ndị ọrịa na-anata ọgwụgwọ Tirzepatid ruru 5% ma ọ bụ oke ibu ibu (79 - 83% vs 32%) (Garvey WT, 2023). N'ime ọmụmụ ihe a, nkezi ịdị arọ 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, Tirzepatid abụghị naanị ibelata ibu ahụ nke ukwuu kamakwa ọ nwere mmetụta dị mma na njikwa glucose ọbara ..
Mmelite nke ọrịa shuga Neuropathy
Nnyocha e mere egosiwo na GLP1-RA 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 nkwarụ ọgụgụ isi. Dị ka abụọ GIP-RA / GLP-1RA, na neuroblastoma cell line (SHSY5Y), nchọpụta achọpụtala na Tirzepatid nwere mmetụta na akara nke neuronal ibu (CREB na BDNF), apoptosis (BAX / Bcl2 ratio), iche (pAkt, MAP2, GAP43, na AGBL4), insulin resistance (GLUT3), na insulin resistance (GLUT3). SORBS1). Nsonaazụ na-ekwusi ike ọrụ Tirzepatid n'ịgbalite ụzọ pAkt/CREB/BDNF na mgbago mgbago mgbago mgbago na arụmọrụ neuroprotective ya, na-egosi na ọ nwere ike igbochi mmetụta ndị metụtara hyperglycemia na nguzogide insulin na ọkwa neuronal. Ya mere, Tirzepatid nwere ike imeziwanye neurodegeneration nke hyperglycemia kpatara ma merie nguzogide insulin nke neuronal, na-enye nghọta ọhụrụ maka mmelite nke neuropathy metụtara metabolism [5]..
Ọganihu nyocha na ọgwụgwọ ụdị 2 metabolism
Dị ka ụdị ọgwụ hypoglycemic ọhụrụ, Tirzepatid abụrụla agonist GIP/GLP-1R nke mbụ akwadoro maka ọgwụgwọ metabolism na United States. Ọtụtụ nnukwu nnwale ụlọ ọgwụ ekwenyela na mbelata glucose ọbara ya dị ịrịba ama na mmetụta mbelata ibu, ma nwee ikike na nchebe obi. Echiche nke peptides sịntetik emeghela ọtụtụ ohere amaghị maka Tirzepatid. Nnwale na-aga n'ihu (NCT04166773) na ihe akaebe na-egosi na ọ bụ ọgwụ na-ekwe nkwa n'ọhịa nke ọrịa imeju na-adịghị egbu egbu (NAFLD), renal na neuroprotection [6] (Ma Z, 2023).
Mmetụta ogologo oge nke Tirzepatid na ahụike obi
Tirzepatid nwere ike ibelata ihe ize ndụ nke ọrịa obi site n'ịkwalite ibu ibu. Otu nnyocha nyochara mmetụta Tirzepatid na oke ibu na ọrịa obi na ọrịa obi na ndị okenye America [7] . Nnyocha ahụ chọpụtara na n'etiti ndị okenye America tozuru oke maka ọgwụgwọ Tirzepatid, mgbe ọgwụgwọ na 15 mg nke Tirzepatid gasịrị, e mere atụmatụ na 70.6% na 56.7% nke ndị okenye tụfuru ≥ 15% na ≥ 20% nke ahụ ha n'otu n'otu, nke pụtara mbelata 58.8% na ọnụ ọgụgụ ndị buru oke ibu. N'ime ndị na-enweghị ọrịa obi, ihe ize ndụ nke ọrịa obi afọ 10 na-ebelata site na 10.1% 'tupu ọgwụgwọ' ruo 7.7% 'mgbe ọgwụgwọ gasịrị', na mbelata ihe ize ndụ zuru oke nke 2.4% na mbelata ihe ize ndụ nke 23.6%, na-egbochi ihe omume ọrịa obi 2 nde.
N'ikpeazụ, Tirzepatid bụ ụdị ọhụrụ nke abụọ agonist nke GIP na GLP-1 ndị na-anabata ya, nke 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 nke pancreatic, na-egbu oge ọganihu nke metabolism, ma nwee mmetụta cardioprotective. N'ịgwọ oke ibu, ọ nwere ike ibelata oriri oriri nke ọma, iwelata agụụ, ịbawanye afọ ojuju, nyere ndị ọrịa buru ibu aka ịkwụsị ibu ibu, 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 ọrịa metabolic na-adịghị mma dị ka steatohepatitis na-adịghị egbu egbu, ọrịa apnea na-ehi ụra, na nkụchi obi, ma nwee ike imeziwanye ọtụtụ ihe ngosi metabolic n'otu oge, na-enye atụmatụ ọgwụgwọ zuru oke. Usoro ịgba ntụtụ ya otu ugboro kwa izu dị mma iji ma nwee ike melite nnabata ọgwụgwọ ndị ọrịa. Site n'ịchịkwa glucose na ịdị arọ nke ọbara n'ụzọ dị irè na ibelata ihe ize ndụ nke nsogbu, ọ nwere ike imeziwanye ọnọdụ anụ ahụ nke ndị ọrịa, mee ka ikike ha na-arụ ọrụ kwa ụbọchị na ịdị mma ndụ ha dịkwuo mma, nwekwuo ntụkwasị obi na njikwa ọrịa, belata ibu uche ha, na imeziwanye mmekọrịta mmadụ na ibe ya.
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 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. O tinyela aka n'ịmụ banyere metabolism metabolism, oke ibu, na nsogbu ndị metụtara ya, na-achọ ikpughe usoro ọgwụgwọ ọhụụ 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 ịkpụzi ụkpụrụ nduzi ụlọ ọgwụ na usoro ọgwụgwọ na ngalaba nke endocrinology na metabolism. Dr. William T. Garvey depụtara n'akwụkwọ ntụaka [4 ].
