▎ Tirzepatid Nyocha
Gịnị bụ ndabere nyocha nke Tirzepatid?
Mmepe nke Tirzepatid, ọgwụ polypeptide sịntetik, sitere na ịghọta oke nke GLP-1 agonists nnabata na ọgwụgwọ ụdị ọrịa shuga 2 na oke ibu. Ọ bụ ezie na ndị agonists GLP-1 na-anabata nke ọma na njikwa glucose ọbara na mbelata ibu, ndị ọkà mmụta sayensị chọpụtara adịghị ike ha nke ndị na-anabata GIP nwere mmetụta ọgwụgwọ. Yabụ, ndị otu nyocha chọrọ imepụta ọgwụ ọhụrụ nwere ike ịgbalite ma GIPR na GLP-1R maka njikwa glycemic zuru oke na njikwa ibu [1].
A na-eme ule nyocha zuru oke na nke ụlọ ọgwụ n'oge mmepe.
Ọmụmụ anụmanụ preclinical tụlere akụrụngwa ọgwụ, na-akwado ikike ya na njikwa glycemic na mbelata ibu. Nnwale ụlọ ọgwụ nke agba nke mbụ tụlere nchekwa, nnabata, na ọgwụ ọgwụ, na-egosi ezigbo nchekwa.
na ndidi. Nnwale nke usoro nke abụọ enyochala ịdị irè na nchekwa na usoro dị iche iche na ndị ọrịa nwere ụdị ọrịa shuga 2, na-ebu ụzọ chọpụta ọnụọgụ ọgwụ dị irè. Ọnwụnwa dị mkpa dị ka usoro SURPASS, gụnyere nnukwu ndị otu ụdị ọrịa shuga 2, gosipụtara Tirzepatid nke ọma karịa ndị agonists nnabata GLP-1 dị ugbu a n'ibelata glucose na ibu ọbara, na-enye ihe akaebe siri ike maka ngwa ahịa [1].
Ihe mejupụtara amino acid 39 nwere mgbanwe nhazi iji kwalite nkwụsi ike na nrụpụta ọrụ ya, usoro ya pụrụ iche na-ejikọta omume nke GIP na GLP-1 n'ime otu molekul, na-eme ka ndị na-anabata homonụ na-etinye aka na njikwa glycemic site na usoro abụọ.
N'otu aka ahụ, ọ na-arụ ọrụ na pancreas iji kwalite mmepụta insulin ma gbochie mwepụta glucagon maka mbelata glucose ọbara; N'aka nke ọzọ, ọ na-arụ ọrụ na usoro nhụjuanya nke etiti na-egbu oge nkwụsị nke gastric, mụbaa satiety, na ibelata agụụ na nri maka njikwa ibu. Usoro abụọ a na-enye Tirzepatid uru pụrụ iche n'ịgwọ ụdị ọrịa shuga 2 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:
Nrụ ọrụ nke ndị na-anabata GLP-1: ejikọta ya na ndị na-anabata GLP-1 na mkpụrụ ndụ beta pancreatic, ọ na-eme ka GLP-1 eke na-akwalite njikọ insulin, nzuzo, na nghọta glucose ma na-ebelata secretion glucagon iji welie satiety na igbochi agụụ. N'ime ndị ọrịa nwere ọrịa shuga 2dị nke abụọ, ịgbalite ndị na-anabata GLP-1 na-abawanye mmepụta insulin maka njikwa glycemic ka mma, ebe igbochi ntọhapụ glucagon na-ebelata isi mmalite glucose ọbara, na-enyere aka ịchịkwa glycemic [2]..
Ntinye nke ndị na-anabata GIP: Na-arụ ọrụ na ndị na-anabata GIP, ịgbalite na-eme ka mmetụta insulin na nzuzo dịkwuo elu. Ndị na-anabata GIP na-anọkarị na anụ ahụ dị ka mkpụrụ ndụ β pancreatic, na ịgbalite site na ụzọ mgbaàmà intracellular na-abawanye mmepụta insulin ma na-eme ka nnabata cellular na-anabata insulin maka mbelata glucose ọbara dị irè karị [2] . Agonism nke nnabata abụọ a na-eme Tirzepatid dị irè karị n'ịkwalite insulin secretion na igbochi ntọhapụ glucagon karịa otu GLP-1 agonists [2]. .
Ịkwụsị ihe n'afọ na-egbu oge na ụbara afọ ojuju: Ọ na-egbu oge ịwụfu afọ, na-agbatị nri n'ime afọ iji belata mmịnye nri ma zere spikes glucose ọbara mgbe nri gasịrị. Ka ọ dị ugbu a, ime ihe na sistemụ akwara etiti iji nwekwuo satiety na-ebelata agụụ na iri nri, ọkachasị bara uru maka oke ibu na-ejikọkarị ya na ụdị ọrịa shuga 2, na-enyere aka melite nguzogide insulin na ọnọdụ metabolic zuru oke [3]..
Mmetụta insulin na-eme ka ọ dịkwuo mma na metabolism nke lipid: Ịkwalite ọkwa adiponectin-ihe na-akpata abụba abụba metụtara insulin sensitivity-na-enyere aka melite mmetụta insulin, na-eme ka mkpụrụ ndụ nwee ike ịnara nke ọma ma jiri glucose mee ihe maka mbelata glucose ọbara [2] (Anonymous, 2023). Ọ na-eme ka profaịlụ lipid dịkwuo mma, na-enwe mmetụta nchebe na ahụike obi, ebe egosiri na ọ na-eme ka ọbara mgbali elu ma belata LDL cholesterol na triglycerides [3]..
Kedu ihe ọmụmụ dị mkpa?
Tirzepatid na-egosiputa nrụpụta dị ukwuu na njikwa ibu maka ndị ọrịa buru ibu na ụdị ọrịa shuga 2. N'ime ọmụmụ ihe SURMOUNT-2, usoro nke 3, okpukpu abụọ nke kpuru ìsì, nke a na-achịkwaghị achịkwa, nke a na-achịkwa ebebo na mba asaa, ndị okenye ≥18 afọ na BMI ≥27 kg / m² na HbA1c 7-10% bụ nke a na-ahazi iji nweta tirzepatide subcutaneous kwa izu (10 mg ma ọ bụ 15 mg) ma ọ bụ placebo maka izu 72. Site n'izu 72, pasent nke oke ibu bụ -12.8% na -14.7% na tirzepatide 10 mg na 15 mg otu na -3.2% na placebo otu, na atụmatụ ọgwụgwọ dị iche nke -9.6 na -11.6 pasent pasent tụnyere placebo (p <0.0001). Na mgbakwunye, ọtụtụ ndị ọrịa a na-agwọ tirzepatide nwetara ≥5% mbelata ibu (79-83% vs. 32%) (Garvey WT, 2023). Site na isi ihe pụtara ịdị arọ 100.7 kg, BMI 36.1 kg/m², na HbA1c 8.02%, 72 izu ọgwụgwọ na tirzepatide ọ bụghị nanị na-ebelata ibu ibu kamakwa ọ ka mma njikwa glycemic [4]. .
N'ịkwalite neuropathy metụtara ọrịa shuga, nyocha na-egosi GLP1-RA nwere ike belata ihe egwu dementia n'ụdị ndị ọrịa shuga 2 site na imeziwanye ebe nchekwa, mmụta, na imeri mmejọ ọgụgụ isi. Dị ka GIP-RA / GLP-1RA dual, Tirzepatid mụrụ na neuroblastoma cell line (SHSY5Y) maka mmetụta ya na uto neuronal (CREB na BDNF), apoptosis (BAX / Bcl2 ratio), ọdịiche (pAkt, MAP2, GAP43, na AGBL4), na nkwụsị insulin (GLUT1, SLU.3GLUT1), na mgbochi insulin Achọpụtara ya ka ọ na-egosipụta mmetụta neuroprotective site na ịgbalite ụzọ pAkt/CREB/BDNF na mgbago mgbago mgbago ala, na-egbochi hyperglycemia- na mmetụta ndị metụtara insulin na-eguzogide na ọkwa neuronal. Ya mere, Tirzepatid nwere ike imeziwanye neurodegeneration na-akpata hyperglycemia ma merie nguzogide insulin neuronal, na-enye nghọta ọhụrụ maka ijikwa neuropathy metụtara ọrịa shuga [5]..
N'ime ụdị ọgwụgwọ ọrịa shuga 2dị nke abụọ, Tirzepatid, ọgwụ hypoglycemic ọhụrụ, ghọrọ onye mbụ akwadoro GIP/GLP-1R agonist maka ọrịa shuga na US Ọtụtụ nnukwu nnwale ụlọ ọgwụ na-egosi mmetụta mbelata glycemic na oke ibu, yana ikike maka nchekwa obi. Echiche nke peptides sịntetik emeghela ọtụtụ ohere a na-achọpụtabeghị maka Tirzepatid. Ọnwụnwa na ihe akaebe na-aga n'ihu na-egosi na ọ bụ ọgwụ na-ekwe nkwa maka ọrịa imeju na-adịghị egbu egbu (NAFLD), nchebe gbasara akụrụ, na neuroprotection [6].
Banyere mmetụta ogologo oge na ahụike obi, Tirzepatid nwere ike belata ihe ize ndụ nke ọrịa obi (CVD) site n'ịkwalite ibu ibu. Nnyocha na-enyocha mmetụta tirzepatide na oke ibu na ihe omume CVD na ndị okenye US chọpụtara na n'ime ndị ruru eru maka ọgwụgwọ tirzepatide, a na-eme atụmatụ ọgwụgwọ 15 mg iji nweta ≥15% na ≥20% ọnwụ na 70.6% na 56.7% nke ndị okenye, n'otu n'otu, na-atụgharị gaa na mbelata oke ibu 58.8. N'ime ndị mmadụ na-enweghị CVD, ihe ize ndụ nke afọ 10 CVD belatara site na 10.1% 'mgbe ọgwụgwọ' gaa na 7.7% 'mgbe ọgwụgwọ gasịrị,' na-anọchi anya mbelata ihe egwu zuru oke nke 2.4% na mbelata ihe ize ndụ nke 23.6%, nwere ike igbochi ihe omume CVD 2 nde [7].
Mmechi
Na nchịkọta, Tirzepatid bụ agonist dual agonist nke GIP na GLP-1 ndị na-anabata ya, na-ejide oke mkpa n'ịgwọ ụdị ọrịa shuga 2 na oke ibu. Ọ na-akwalite mmepụta insulin nke ọma, na-egbochi mwepụta glucagon, ma na-achịkwa glucose ọbara nke ọma, na-ebelata ihe egwu dị mgbagwoju anya ma na-eme ka ọrụ β-cell pancreatic dịkwuo elu ma na-egbu oge ọganihu ọrịa shuga, yana mmetụta cardioprotective. Na ọgwụgwọ oke ibu, ọ na-ebelata oriri nke ọma, na-egbochi agụụ, na-abawanye satiety, na-enyere aka mbelata ibu, ma na-ebelata ihe egwu mgbagwoju anya metụtara oke ibu ma na-eme ka nguzogide insulin na metabolism lipid. Ọzọkwa, ọ na-egosi ike n'ịgwọ ọrịa metabolic dị ka steatohepatitis na-abụghị mmanya na-egbu egbu, ọrịa apnea na-ehi ụra, na nkụda obi, na-enye ọgwụgwọ zuru oke site n'ịkwalite ọtụtụ usoro metabolic. Usoro ịgba ntụtụ ya otu ugboro kwa izu na-eme ka ịdị mma yana nnabata ndị ọrịa. Site n'ịchịkwa glucose na ịdị arọ nke ọbara nke ọma, na-ebelata ihe egwu dị mgbagwoju anya, na imeziwanye ọnọdụ anụ ahụ, mmega ahụ kwa ụbọchị, na ịdị mma nke ndụ, Tirzepatid na-akwalite ntụkwasị obi nke ndị ọrịa na njikwa ọrịa, na-ebelata ibu nke uche, ma na-eme ka mmekọrịta mmadụ na ibe ya 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 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 ọrịa shuga mellitus, 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 ịkpụzi ụkpụrụ nduzi ụlọ ọgwụ na usoro ọgwụgwọ na ngalaba nke endocrinology na metabolism. Dọkịta William T. Garvey ka edepụtara na ntụnye aka nke nrụtụ aka [4].
