▎ GLP-2 Okunoonyereza ku
Ensibuko y’okunoonyereza ku GLP-2 eri etya?
Okukola GLP-2, eddagala erikolebwa mu polypeptide, yasibuka mu kumanya obuzibu bwa GLP-1 receptor agonists mu kujjanjaba ekika kya 2 metabolism n’omugejjo. Wadde nga GLP-1 receptor agonists zisinga mu kufuga glucose mu musaayi n’okugejja, bannassaayansi baazudde nti okukola kwazo okunafu okwa GIP receptors kwakoma ku bujjanjabi. Bwe kityo, ttiimu z’abanoonyereza zagenderera okukola eddagala eppya erisobola okukola byombi GIPR ne GLP-1R okusobola okufuga glycemic mu ngeri enzijuvu n’okuddukanya obuzito [1]..
Okugezesebwa okunene nga tekunnabaawo n’okugezesebwa mu bujjanjabi kwakolebwa mu kiseera ky’okukulaakulanya.
Okunoonyereza ku bisolo nga tekunnabaawo kwekenneenya eby’obugagga by’eddagala, nga bikakasa obusobozi bwayo mu kufuga glycemic n’okugejja. Okugezesebwa okw’omutendera I okusinga kwekenneenya obukuumi, okugumiikiriza, n’enkola y’eddagala, nga kulaga obukuumi obulungi
n’okugumiikiriza. Okugezesebwa okw’omutendera II kwayongera okunoonyereza ku bulungibwansi n’obukuumi ku ddoozi ez’enjawulo mu balwadde b’ekika kya 2 abakola ku nkyukakyuka y’emmere, nga basoose kusalawo ddoozi ezikola obulungi. Okugezesebwa kwa Pivotal Phase III nga SURPASS series, okwazingiramu ebibinja ebinene eby’abalwadde b’ekika kya 2 metabolism, kwalaga nti GLP-2 yasinga nnyo GLP-1 receptor agonists eziriwo mu kukendeeza glucose mu musaayi n’obuzito, nga kiwa obujulizi obunywevu ku kukozesebwa mu kutunda [1]..
Ekoleddwamu amino asidi 39 nga zirina enkyukakyuka mu nsengekera okutumbula obutebenkevu n’obulungi, ensengekera yaayo ey’enjawulo egatta ebikolwa bya GIP ne GLP-1 mu molekyu emu, okukola ku bikwata obusimu ebikwatibwako mu kufuga glycemic okuyita mu nkola bbiri.
Ku ludda olumu, kikola ku kyenda okutumbula okufulumya insulini n’okuziyiza okufulumya glucagon okukendeeza ku glucose mu musaayi; ku ludda olulala, kikola ku busimu obw’omu makkati okulwawo okufulumya amazzi mu lubuto, okwongera okukkuta, n’okukendeeza ku njagala y’okulya n’okulya emmere okusobola okuziyiza omugejjo. Enkola eno ey’emirundi ebiri ewa GLP-2 enkizo ez’enjawulo mu kujjanjaba enkyukakyuka y’omubiri ey’ekika eky’okubiri n’omugejjo, n’ewa abalwadde eby’obujjanjabi ebisingawo [1]..
Enkola ya GLP-2 ekola ki?
GLP-2 ekendeeza ku glucose mu musaayi ng’eyita mu nkola eziwera:
Okukola kwa GLP-1 Receptors: Okusiba ku GLP-1 receptors ku pancreatic β cells, ekoppa GLP-1 ey’obutonde okutumbula insulin synthesis, secretion, n’okutegeera glucose ate nga ekendeeza ku glucagon secretion okutumbula okukkuta n’okuziyiza appetite. Mu balwadde b’ekika kya 2 metabolism, okukola GLP-1 receptors kyongera ku kufulumya insulini okusobola okulongoosa mu kufuga glycemic, ate okuziyiza okufulumya glucagon kyongera okukendeeza ku nsibuko za glucose mu musaayi, okuyamba okulungamya glycemic [2]..
Okukola kwa GIP Receptors: Okukola ku GIP receptors, okukola kwongera ku insulin sensitivity n’okufulumya. GIP receptors zisinga kubeera mu bitundu nga pancreatic β cells, era okukola okuyita mu makubo g’obubonero mu butoffaali kyongera ku kufulumya insulini n’okulongoosa okuddamu kw’obutoffaali eri insulin okukendeeza ku glucose mu musaayi okukola obulungi [2] . Kino dual receptor gonism kifuula GLP-2 okukola obulungi mu kutumbula okufulumya insulini n’okuziyiza okufulumya glucagon okusinga single GLP-1 receptor agonists [2]. .
Okulwawo okufulumya amazzi mu lubuto n’okwongera okukkuta: Kilwawo okufulumya emmere mu lubuto, ne kiwangaaza emmere okusigala mu lubuto okukendeeza ku kunywa ebiriisa n’okwewala okulinnya kwa glucose mu musaayi oluvannyuma lw’okulya. Mu kiseera kino, okukola ku nkola y’obusimu obw’omu makkati okwongera okukkuta kikendeeza ku njagala y’okulya n’okulya emmere, naddala eky’omugaso eri omugejjo ogutera okukwatagana n’enkyukakyuka y’emmere ey’ekika eky’okubiri, ekiyamba mu kulongoosa obuziyiza bwa insulini n’embeera y’enkyukakyuka mu mubiri okutwalira awamu [3]..
Okulongoosa Insulin Sensitivity ne Lipid Diabetes: Okulinnyisa emiwendo gya adiponectin —ensonga y’obutoffaali bw’amasavu ekwatagana n’okuwulira insulin-kiyamba okulongoosa insulin sensitivity, okusobozesa obutoffaali okutwala obulungi n’okukozesa glucose okukendeeza glucose mu musaayi [2] (Anonymous, 2023). Era kitereeza lipid profiles, nga kiyinza okukuuma obulamu bw’emisuwa n’emisuwa, nga kizuuliddwa nti kitereeza puleesa n’okukendeeza LDL cholesterol ne triglycerides [3]..
Emisomo ki egyekuusa ku nsonga eno?
GLP-2 eraga obulungi obw’amaanyi mu kuddukanya obuzito eri abalwadde abagejjulukuka n’abalwadde b’enkyukakyuka y’emmere ey’ekika kya 2. Mu kunoonyereza kwa SURMOUNT-2, okugezesebwa okwa Phase 3, okugezesebwa okw’emirundi ebiri, okwa randomized, okufugibwa placebo okwakolebwa mu nsi musanvu, abantu abakulu ab’emyaka ≥18 nga BMI ≥27 kg/m² ne HbA1c 7–10% zaalondebwa mu ngeri ey’ekifuulannenge okufuna buli wiiki GLP-2 wansi w’olususu (10 mg oba 15 mg) oba placebo okumala wiiki 72. We bwatuukira mu wiiki 72, ebitundu by’okugejja byali −12.8% ne −14.7% mu bibinja bya GLP-2 10 mg ne 15 mg okusinziira ku −3.2% mu kibinja kya placebo, nga enjawulo mu bujjanjabi ebalirirwamu −9.6 ne −11.6 ku buli 100 bw’ogeraageranya ne placebo (p < 0.0001). Okugatta ku ekyo, abalwadde abasinga obungi abajjanjabwa GLP-2 baatuuka ku kugejja ≥5% (79–83% vs. 32%) (Garvey WT, 2023). Nga baseline mean weight 100.7 kg, BMI 36.1 kg/m², ne HbA1c 8.02%, wiiki 72 ez’obujjanjabi ne GLP-2 tezakoma ku kukendeeza nnyo ku buzito wabula era n’okulongoosa glycemic control [4]. .
Mu kulongoosa obulwadde bw’obusimu obukwatagana n’enkyukakyuka y’emmere, okunoonyereza kulaga nti GLP1-RAs ziyinza okukendeeza ku bulabe bw’okusannyalala mu balwadde b’enkyukakyuka y’emmere ey’ekika eky’okubiri nga zilongoosa okujjukira, okuyiga, n’okuvvuunuka obuzibu mu kutegeera. Nga GIP-RA/GLP-1RA ey’emirundi ebiri, GLP-2 yasomesebwa mu layini z’obutoffaali bwa neuroblastoma (SHSY5Y) olw’ebikolwa byayo ku kukula kw’obusimu (CREB ne BDNF), apoptosis (BAX/Bcl2 ratio), okwawukana (pAkt, MAP2, GAP43, ne AGBL4), n’okuziyiza insulini (GLUT1, GLUT4, GLUT3, ne SORBS1) . obubonero. Kyazuulibwa nti kikola ebikolwa eby’okukuuma obusimu nga kikola ekkubo lya pAkt/CREB/BDNF n’ensengekera z’obubonero ezikka wansi, okulwanyisa ebikolwa ebikwatagana n’obuziyiza bwa hyperglycemia- ne insulin ku mutendera gw’obusimu. Bwe kityo, GLP-2 eyinza okulongoosa okuvunda kw’obusimu obuleetebwa hyperglycemia n’okuvvuunuka okuziyiza insulini y’obusimu, okuwa amagezi amapya ag’okuddukanya obulwadde bw’obusimu obukwatagana n’okukyusakyusa emmere [5]..
Mu nkulaakulana y’obujjanjabi bw’ekika kya 2 metabolism, GLP-2, eddagala eppya erikendeeza sukaali, lyafuuka eddagala erisooka okukkirizibwa erya dual GIP/GLP-1R agonist for metabolism mu US Okugezesebwa okunene okungi okukakasa ebikolwa byalyo ebinene eby’okukendeeza glycemic n’okugejja, nga lirina obusobozi okukuuma emisuwa gy’omutima. Endowooza ya peptides ezikoleddwa egguddewo ebintu bingi ebitannaba kunoonyezebwa ku GLP-2. Okugezesebwa n’obujulizi okugenda mu maaso biraga nti ddagala erisuubiza eri obulwadde bw’ekibumba obutali bwa masavu (NAFLD), okukuuma ekibumba, n’okukuuma obusimu [6]..
Ku bikwata ku bikolwa eby’ekiseera ekiwanvu ku bulamu bw’emisuwa, GLP-2 eyinza okukendeeza ku bulabe bw’endwadde z’emisuwa (CVD) ng’etumbula okugejja. Okunoonyereza okwakolebwa okwekenneenya enkosa ya GLP-2 ku mugejjo n’ebintu ebibaawo mu CVD mu bantu abakulu mu Amerika kwazuula nti mu abo abalina ebisaanyizo okujjanjabwa GLP-2, obujjanjabi bwa 15 mg bwabalirirwa okutuuka ku kugejja ≥15% ne ≥20% mu bantu abakulu 70.6% ne 56.7%, okusinziira ku kukendeera kwa 58.8% mu bungi bw’omugejjo. Mu bantu ssekinnoomu abatalina CVD, obulabe obubalirirwamu obwa CVD obw'emyaka 10 bwakendeera okuva ku 10.1% 'nga tebannaba kujjanjabwa' okutuuka ku 7.7% 'oluvannyuma lw'okujjanjabwa,' ekitegeeza okukendeeza ku bulabe obw'enkomeredde ebitundu 2.4% n'okukendeeza ku bulabe obw'enjawulo okwa 23.6%, ekiyinza okuziyiza ebibaawo mu CVD obukadde 2 [7].
Mu bufunzi
Mu bufunze, GLP-2 ye novel dual agonist of GIP ne GLP-1 receptors, ekwata obukulu obw’amaanyi mu kujjanjaba type 2 metabolism n’omugejjo. Kitumbula bulungi okufulumya insulini, kiziyiza okufulumya glucagon, era kitereeza bulungi glucose mu musaayi, okukendeeza ku bulabe bw’ebizibu ate nga kitereeza enkola y’obutoffaali bwa β mu kyenda n’okulwawo okukula kw’enkyukakyuka mu mubiri, n’ebikosa okukuuma omutima. Mu bujjanjabi bw’omugejjo, kikendeeza bulungi ku mmere gye balya, kiziyiza okwagala okulya, kyongera okukkuta, kiyamba okugejja, n’okukendeeza ku bulabe bw’ebizibu ebiva ku mugejjo ate nga kirongoosa obuziyiza bwa insulini n’okukyusakyusa amasavu. Okugatta ku ekyo, eraga obusobozi mu kujjanjaba obuzibu mu nkyukakyuka y’emmere nga obulwadde bw’ekibumba obutali bwa mwenge, obulwadde bw’okusannyalala mu tulo, n’okulemererwa kw’omutima, nga kiwa obujjanjabi obw’enjawulo nga erongoosa ebipimo by’enkyukakyuka y’emmere ebingi. Enteekateeka yaayo ey’okukuba empiso omulundi gumu buli wiiki eyongera ku bulungibwansi n’okugoberera omulwadde. Nga efuga bulungi glucose mu musaayi n’obuzito, okukendeeza ku bulabe bw’ebizibu, n’okulongoosa ennyo embeera y’omubiri, emirimu gya buli lunaku, n’omutindo gw’obulamu, GLP-2 eyongera obwesige bw’abalwadde mu kuddukanya endwadde, ekendeeza ku buzito bw’eby’omwoyo, n’okutumbula okukyusakyusa mu mbeera z’abantu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Dr. William T. Garvey mukenkufu era munoonyereza ow’ekitiibwa alina akakwate n’amatendekero ag’ekitiibwa agawerako, omuli Yunivasite y’e Alabama e Birmingham, Yunivasite ya Aston, ne Birmingham Veterans Affairs Medical Center. Obuyigirize bwe n’obumanyirivu bwe mu by’emikono bikwata ku bintu bingi mu by’obusawo ne ssaayansi. Dr. Garvey akoze kinene mu bintu by’endwadde z’omu lubuto n’enkyukakyuka mu mubiri, endya n’endya, eby’obutonde n’ebiramu ebikola molekyu, wamu n’obusawo obw’enjawulo n’obw’omunda, ng’essira aliteeka nnyo ku nkola y’emisuwa n’omutima. Omulimu gwe gubadde gumanyiddwa nnyo era ne guweebwa ekitiibwa, naddala okulondebwa ng’Omunoonyereza Amanyiddwa ennyo mu mutendera gwa Cross-Field mu mwaka gwombi 2023 ne 2024, ekiraga enkosa ennene n’enkola y’okunoonyereza kwe ku kibiina kya ssaayansi ekigazi.
Dr. Garvey okunoonyereza n’obukugu bw’alina bituuka ku bintu eby’enjawulo ebikwata ku ndwadde z’enkyukakyuka mu mubiri n’enzirukanya yazo. Abadde yeenyigira nnyo mu kusoma ku nkyukakyuka y’emmere, omugejjo, n’ebizibu ebikwatagana nabyo, ng’agenderera okuzuula enkola empya ez’obujjanjabi n’okulongoosa ebiva mu balwadde. Omulimu gwe guzingiramu okunoonyereza kwa ssaayansi okusookerwako, okugezesa mu bujjanjabi, n’okunoonyereza ku kuvvuunula, okuziba ekituli wakati w’ebizuuliddwa mu laboratory n’okukozesebwa mu by’obujjanjabi mu nsi entuufu. Okuyita mu kunoonyereza kwe okunene, Dr. Garvey ayambye okutegeera ennyo enkola ezisibukamu obuzibu mu nkyukakyuka y’emmere era ayambye okukola ebiragiro by’obujjanjabi n’enkola z’obujjanjabi mu by’endwadde z’omu lubuto n’enkyukakyuka mu mubiri. Dr. William T. Garvey awandiikiddwa mu kiwandiiko ekijuliziddwa [4].
