▎ Tirzepatide Nyocha
Kedu ihe ndabere nyocha nke Tirzepatide?
Mmepe nke Tirzepatide, ọgwụ polypeptide sịntetik, sitere n'ịghọta oke nke GLP-1 agonists nnabata na ọgwụgwọ ụdị 2 metabolism 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 abụọ nyochara arụmọrụ na nchekwa n'ụdị dị iche iche n'ụdị ndị ọrịa metabolism nke 2, na-ebu ụzọ chọpụta ọnụọgụ ọgwụ dị mma. Ọnwụnwa dị mkpa dị ka usoro SURPASS, gụnyere nnukwu ndị otu ụdị 2 ndị ọrịa metabolism, gosipụtara na Tirzepatide gosipụtara 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 welie nkwụsi ike na ịdị irè, 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 Tirzepatide uru pụrụ iche n'ịgwọ ụdị 2 metabolism na oke ibu, na-enye ndị ọrịa nhọrọ ọgwụgwọ zuru oke [1].
Kedu ihe bụ usoro nke Tirzepatide?
Tirzepatide 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-eṅomi GLP-1 eke iji kwalite njikọ insulin, nzuzo, na mmetụta glucose na-ebelata secretion glucagon iji welie satiety na igbochi agụụ. N'ime ndị ọrịa na-arịa ọrịa shuga 2, 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 Tirzepatide 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 satiety: 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 sistemu akwara etiti iji mụbaa satiety na-ebelata agụụ na iri nri, ọkachasị bara uru maka oke ibu na-ejikọta ya na ụdị 2 metabolism, na-enyere aka melite nguzogide insulin na ọnọdụ metabolic zuru oke [3]..
Mmetụta insulin na-eme ka ọ dịkwuo mma na ọrịa shuga: 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-emekwa 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 ndị dị mkpa?
Tirzepatide na-egosiputa nrụpụta dị ukwuu na njikwa ibu maka ndị ọrịa nwere oke ibu na ụdị 2. N'ime ọmụmụ ihe SURMOUNT-2, usoro nke 3, ndị ìsì abụọ, nke a na-achịkwaghị achịkwa, 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 nata 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%, ọgwụgwọ izu 72 na tirzepatide ọ bụghị naanị na-ebelata ibu mana ọ na-emeziwanye njikwa glycemic [4]. .
N'ịkwalite neuropathy metụtara metabolism, nyocha na-egosi GLP1-RA nwere ike ibelata ihe egwu dementia na ụdị 2 ndị ọrịa metabolism site na imeziwanye ebe nchekwa, mmụta, na imeri mmejọ ọgụgụ isi. Dị ka GIP-RA / GLP-1RA abụọ, Tirzepatide 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.3GLT1), 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, Tirzepatide nwere ike imeziwanye neurodegeneration na-akpata hyperglycemia ma merie nguzogide insulin neuronal, na-enye nghọta ọhụrụ maka ijikwa neuropathy metụtara metabolism [5]..
N'ime ụdị ọgwụgwọ ọgwụgwọ metabolism nke 2, Tirzepatide, ọgwụ hypoglycemic ọhụrụ, ghọrọ agonist abụọ GIP / GLP-1R nke izizi akwadoro maka metabolism na US Ọtụtụ nnukwu nnwale ụlọ ọgwụ na-akwado mmetụta mbelata glycemic na oke ibu, yana ikike maka nchekwa obi. Echiche nke peptides sịntetik emeghela ọtụtụ ohere a na-achọpụtabeghị maka Tirzepatide. Nnwale 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, Tirzepatide 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 tozuru oke 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 na mbelata oke ibu 58.8. N'ime ndị mmadụ n'otu n'otu 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, Tirzepatide bụ akwụkwọ akụkọ dual agonist nke GIP na GLP-1 ndị na-anabata ya, na-ejide ihe dị mkpa n'ịgwọ ụdị 2 metabolism 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 na-egbu oge na-egbu oge na-aga n'ihu na metabolism, yana mmetụta cardioprotective. Na ọgwụgwọ oke ibu, ọ na-ebelata oriri nke ọma, na-egbochi agụụ, na-abawanye satiety, na-enyere aka mbelata ibu arọ, 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, ọrịa apnea na-ehi ụra, na nkụda mmụọ, 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, ọrụ ụbọchị na ịdị mma nke ndụ, Tirzepatide 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 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. Dọkịta William T. Garvey ka edepụtara n'akwụkwọ ntụaka [4].
