▎ GLP-2 Nchọpụta
Kedu ihe ndabere nyocha nke GLP-2?
Mmepe nke GLP-2, 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 nke III dị ka usoro SURPASS, gụnyere nnukwu ndị otu ụdị 2 ndị ọrịa metabolism, gosipụtara GLP-2 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 na igbochi 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 GLP-2 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 GLP-2?
GLP-2 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 GLP-2 dị irè karị n'ịkwalite mmepụta insulin 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 dị mkpa?
GLP-2 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 nweta GLP-2 subcutaneous kwa izu (10 mg ma ọ bụ 15 mg) ma ọ bụ placebo maka izu 72. Ka ọ na-erule izu 72, pasentị mbelata ibu bụ -12.8% na -14.7% na GLP-2 10 mg na 15 mg otu na -3.2% n'ime otu placebo, na atụmatụ ọgwụgwọ dị iche nke -9.6 na -11.6 pasent pasent tụnyere placebo (p <0.0001). Na mgbakwunye, ọtụtụ ndị ọrịa GLP-2 gwọchara nwetara ≥5% mbelata ibu (79-83% vs. 32%) (Garvey WT, 2023). Site na isi ihe pụtara 100.7 kg, BMI 36.1 kg/m², na HbA1c 8.02%, ọgwụgwọ izu 72 na GLP-2 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 ihe abụọ GIP-RA / GLP-1RA, GLP-2 a mụrụ na neuroblastoma cell ahịrị (SHSY5Y) maka mmetụta ya na neuronal uto (CREB na BDNF), apoptosis (BAX / Bcl2 ratio), iche (pAkt, MAP2, GAP43, na AGBL4), na insulin resistance (GLUT1, 4ORLU.GLUT1). 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, GLP-2 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 metabolism nke 2, GLP-2, ọgwụ hypoglycemic novel, ghọrọ onye mbụ akwadoro GIP/GLP-1R agonist 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 GLP-2. 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, GLP-2 nwere ike ibelata ọrịa obi (CVD) site n'ịkwalite ibu ibu. Nnyocha na-enyocha mmetụta GLP-2 na oke ibu na ihe omume CVD na ndị okenye US chọpụtara na n'ime ndị tozuru oke maka ọgwụgwọ GLP-2, 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 nke 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, GLP-2 bụ akwụkwọ akụkọ dual agonist nke GIP na GLP-1 ndị na-anabata ya, na-ejide nnukwu 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 n'ọbara nke ọma, na-ebelata ihe egwu mgbagwoju anya, na imeziwanye ọnọdụ anụ ahụ, mmega ahụ kwa ụbọchị, na ịdị mma nke ndụ, GLP-2 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 na ntụnye aka nke nrụtụ aka [4].
