Bya Cocer Peptides 
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EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza kwokka mu kisenge (in vitro research). Okunoonyereza mu kisenge (in vitro research) (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okulaba ebikwata ku GLP-1
GLP-1 ye nkola empya eringa glucagon eya peptide-1 receptor agonist (GLP-1 RA). Glucagon-like peptide-1 (GLP-1) ye hormone efulumizibwa mu butonde omubiri gw’omuntu ekola kinene mu kulungamya glucose mu musaayi. Omuwendo gwa glucose mu musaayi bwe gulinnya, GLP-1 efuluma era n’etereeza emiwendo gya glucose mu musaayi ng’eyita mu nkola ez’enjawulo. Wabula mu balwadde ba ssukaali, okufulumya GLP-1 kutera obutamala oba ebivaamu tebimala. GLP-1 yeekwata ku bikwata GLP-1, n’ekoppa ebikolwa by’omubiri ebya GLP-1, bwe kityo n’ekola ebikolwa eby’obujjanjabi ku nkyukakyuka y’emmere n’okuddukanya obuzito.
Ekifaananyi 1 Obujjanjabi bw’omugejjo n’engeri gye bukwata ku kugejja
Omulimu gwa GLP-1 mu Bujjanjabi bwa Ssukaali
Okutumbula Okufulumya Insulin
Mu mbeera z’omubiri, glucose mu musaayi bw’alinnya, obutoffaali bwa enteroendocrine mu kyenda bufulumya GLP-1. GLP-1 yeekwata ku bikwata GLP-1 ku ngulu w’obutoffaali bwa β obw’olubuto, n’ekola amakubo agawerako agalaga obubonero okwongera ku kufulumya insulini. GLP-1 era esobola okwesiba mu ngeri ey’enjawulo ku bikwata GLP-1 ku ngulu w’obutoffaali bwa β obw’olubuto, n’esitula okufulumya insulini mu ngeri eyeesigama ku bungi bwa glucose. Kino kitegeeza nti glucose mu musaayi bw’alinnya, GLP-1 etumbula bulungi okufulumya insulini okukendeeza ku glucose mu musaayi; emiwendo gya glucose mu musaayi bwe giba mu kigero ekya bulijjo, ekikolwa kyayo ku kutumbula okufulumya insulini kiba kinafu, bwe kityo ne kikendeeza ku bulabe bw’okukendeera kwa sukaali mu musaayi. Okunoonyereza kulaga nti oluvannyuma lw’okujjanjabwa ne GLP-1, emiwendo gya insulini gy’abalwadde gitereera nnyo, era emiwendo gya glucose mu musaayi gisobola okufugibwa obulungi.
Ekifaananyi 2: Enkola eyesigamiziddwa ku buzito obw’okungulu okusinziira ku nkola ey’okussa wansi, glucose, n’enkola y’okukyusakyusa omutima. Enzijanjaba ezesigamiziddwa ku Incretin zakola dda ku mutendera ogusinga okubeera waggulu.
Okwawukana ku bikozesebwa mu kufulumya insulini eby’ekinnansi, nga sulfonylureas, ebizimba obutasalako okufulumya insulini awatali kulowooza ku miwendo gya glucose mu musaayi era nga biyinza okwongera ku bulabe bw’okukendeera kwa sukaali mu musaayi, GLP-1’s glucose-concentration-dependent insulin secretion properties esobozesa okukendeeza obulungi emiwendo gya glucose mu musaayi ate nga kikendeeza nnyo ku mirundi gy’okukendeera kwa sukaali mu musaayi, n’ewa eky’okulonda ekisinga obukuumi era ekikola obulungi eky’okufuga glucose mu musaayi abalwadde b’enkyukakyuka y’emmere.
Okuziyiza okufulumya kwa glucagon
Glucagon busimu obufulumizibwa obutoffaali bwa α obw’olubuto obulinnyisa emiwendo gya glucose mu musaayi, nga bukola ekintu ekikontana ne insulini. Mu balwadde ba ssukaali, okufuluma kwa glucagon kutera okusigala nga tekuziyiziddwa ne bwe kiba nti glucose mu musaayi ali waggulu. GLP-1 ekola ku bikwata GLP-1 ku butoffaali bwa α obw’olubuto okuziyiza okufulumya glucagon. Okufulumya glucagon bwe kukendeera, enkola z’ekibumba eza glycogenolysis ne gluconeogenesis ziziyizibwa, ne kikendeeza ku kukola glucose munda n’okwongera okukkakkanya ku glucose mu musaayi. Bannasayansi bakakasizza nti mu balwadde ba type 2 metabolism abajjanjabwa ne GLP-1, emiwendo gya glucagon mu plasma gikendeera nnyo, ekikendeeza bulungi glucose mu kibumba era nga kikola kinene nnyo mu kutebenkeza emiwendo gya glucose mu musaayi.
Okulwawo okufulumya amazzi mu lubuto
GLP-1 ekola ku bikwata GLP-1 mu nkola y’olubuto okukendeeza ku kufuluma kw’olubuto. Okufuluma amangu mu lubuto kireetera emmere okuyingira amangu mu kyenda ekitono ekivaako glucose mu musaayi okulinnya amangu. Mu kulwawo okufulumya amazzi mu lubuto, emmere esigala mu lubuto okumala ebbanga eddene n’eyingira mu kyenda ekitono mpola, ekivaamu okunyiga glucose mpolampola n’okuziyiza okulinnya okw’amaanyi mu glucose mu musaayi oluvannyuma lw’okulya. Ekikolwa kino kiyamba okukuuma omutindo gwa glucose mu musaayi nga gutebenkedde oluvannyuma lw’okulya n’okukendeeza ku nkyukakyuka za glucose mu musaayi. Mu kugezesebwa okumu okw’obujjanjabi, abalwadde abajjanjabwa ne GLP-1 baafuna okukendeera okw’amaanyi mu ntikko za glucose mu musaayi oluvannyuma lw’okulya n’enkyukakyuka entonotono eza glucose mu musaayi, okulongoosa omutindo gw’okufuga glucose mu musaayi okutwalira awamu. Okugatta ku ekyo, okulwawo okufulumya amazzi mu lubuto kuyinza okuleetera omuntu okuwulira ng’ajjudde, ne kiyamba okukendeeza ku mmere gy’olya era bwe kityo ne kiyamba mu kufuga glucose mu musaayi n’okuddukanya obuzito okuva mu ngeri endala.
Ekifaananyi 3: Enkola ya GLP-1 ey’okuddukanya omugejjo
Okulongoosa Enkola ya β-Cell
Obulwadde bwa sukaali obutawona busobola okwonoona obutoffaali bwa β obw’olubuto, ekivaako okukendeera mpolampola emirimu. GLP-1 tekoma ku kukendeeza ssukaali mu musaayi ng’etumbula okufulumya insulini wabula era ekuuma n’okuddaabiriza obutoffaali bwa β obw’olubuto, bwe kityo n’elongoosa enkola y’obutoffaali bwa β. Okunoonyereza kwa ssaayansi kulaga nti GLP-1 eyinza okukola amakubo agamu agalaga obubonero mu butoffaali okutumbula okukula kw’obutoffaali bwa β, okuziyiza okufa kw’obutoffaali bwa β, bwe kityo n’eyongera ku muwendo n’enkola y’obutoffaali bwa β. Mu kugezesa ebisolo n’okunoonyereza okumu mu bujjanjabi, kyazuulibwa nti oluvannyuma lw’okukozesa GLP-1, obusobozi bw’okufulumya insulini obw’obutoffaali bwa β bwayongera, era okuziyiza insulini ne kulongooka. Kino kya makulu nnyo mu bujjanjabi obw’ekiseera ekiwanvu obw’ekika kya 2 metabolism, kubanga kiyamba okukendeeza ku kukula kw’obulwadde n’okukendeeza ku bulabe bw’ebizibu bya sukaali.
Okukozesa GLP-1 mu Bujjanjabi bwa Ssukaali
GLP-1 erina enkola ez’enjawulo ez’okukozesa mu kujjanjaba metabolism. Ku balwadde abapya abazuuliddwa nga bakola ku nkyukakyuka y’emmere ey’ekika kya 2, singa emiwendo gya glucose mu musaayi tegilinnya nnyo era nga tewali bizibu bya maanyi byeyoleka oba endwadde endala ez’amaanyi ezikwatagana, obujjanjabi obumu ne GLP-1 busobola okulowoozebwako. Okunoonyereza mu bujjanjabi kulaga nti abalwadde abamu abaakazuulibwa baafuna okukendeera okw’amaanyi mu miwendo gya hemoglobin A1c (HbA1c) n’okugejja oluvannyuma lw’ekiseera nga bajjanjabwa eddagala erimu. Okugeza, mu kunoonyereza okwa PIONEER series, abalwadde abajjanjabwa n’obujjanjabi bwa GLP-1 obw’omu kamwa baafuna okukendeera okw’amaanyi mu miwendo gya HbA1c bw’ogeraageranya n’ekibinja kya placebo, nga balina obukuumi obulungi n’okugumiikiriza. Ekirungi ky’obujjanjabi obw’ekimu kiri nti yeewala akabi k’okukwatagana kw’eddagala obukwatagana n’obujjanjabi obw’omugatte, era okubuweebwa mu ngeri ennyangu kiyamba okulongoosa omulwadde okunywerera ku bujjanjabi.
GLP-1 era esobola okukozesebwa ng’egatta wamu n’eddagala eddala. Bwe kigattibwa ne metformin, eddagala erisooka erijjanjaba enkyukakyuka y’omubiri ey’ekika eky’okubiri, liyamba okuziyiza insulini n’okukendeeza ku glucose mu kibumba. Eddagala lino zombi lirina enkola ezikwatagana, ezisobozesa okufuga obulungi glucose mu musaayi. Okunoonyereza kulaga nti enkola eno ey’okugatta eyongera okukendeeza ku miwendo gya HbA1c era kivaamu okugejja ennyo. Okugeza, mu kugezesebwa okumu okw’obujjanjabi, abalwadde abajjanjabwa ne metformin abaagattako GLP-1 baafuna okukendeera okunene mu miwendo gya HbA1c bw’ogeraageranya n’abo abaagenda mu maaso n’obujjanjabi bwa metformin monotherapy, awamu n’okugejja okusingawo, awatali kweyongera kwa maanyi mu bulabe bwa ssukaali mu musaayi. Enkola eno esaanira abalwadde abatafugibwa bulungi glucose mu musaayi nga bakozesa eddagala lya metformin monotherapy.
Ku balwadde abalina ekika kya 2 metabolism abalina glucose mu musaayi omungi era nga beetaaga obujjanjabi bwa insulini, okugattako GLP-1 mu bujjanjabi bwa insulini kiyinza okukendeeza ku ddoozi ya insulini. Mu bujjanjabi bwa insulini, abalwadde batera okufuna ensonga ng’okugejja n’okwongera ku bulabe bw’okukendeera kwa sukaali mu musaayi. Bwe kikozesebwa awamu, ebikolwa bya GLP-1 eby’okutumbula okufulumya insulini n’okuziyiza okufulumya kwa glucagon bisobola okulongoosa enkozesa ya insulini, okukendeeza ku ddoozi, era bwe kityo ne kikendeeza ku bulabe bw’okugejja n’okukendeeza ku sukaali mu musaayi. Okugeza, mu kunoonyereza okumu okwakolebwa mu bujjanjabi, abalwadde abaagattako GLP-1 ku bujjanjabi bwabwe obwa insulini baafuna okukendeera kwa wakati mu ddoozi ya insulini, awamu n’okwongera okukendeera mu miwendo gya HbA1c, okugejja, n’okukendeera mu mirundi gy’okukendeera kwa sukaali mu musaayi.
GLP-1 era esobola okukozesebwa nga egattibwa wamu n’eddagala eddala eriweweeza ku ssukaali nga SGLT2 inhibitors. Ebiziyiza SGLT2 bikendeeza ku glucose mu musaayi nga bitumbula okufulumya glucose mu musulo. Okugatta ebibiri bino kiyinza okwongera okulongoosa okufuga kwa glucose mu musaayi nga kiyita mu nkola ez’enjawulo era kiyinza n’okuba n’ebikosa okukwatagana mu kuddukanya obuzito.
Omulimu gwa GLP-1 mu kuddukanya obuzito
Okuziyiza okwagala okulya
GLP-1 ekola ku bikwata GLP-1 mu nkola y’obusimu obw’omu makkati naddala mu hypothalamus. Hypothalamus kitundu kikulu mu mubiri okutereeza okwagala okulya n’okutebenkeza amaanyi. Oluvannyuma lw’okusiba ku bikwata GLP-1 mu hypothalamus, GLP-1 esobola okulung’amya okufuluma kw’obusimu obuyitibwa neuropeptides, gamba ng’okukendeeza ku kufuluma kwa neuropeptide Y (NPY), nga eno nsonga ya maanyi esitula okwagala okulya. Okugatta ku ekyo, GLP-1 eyinza okwongera ku mirimu gy’obusimu obuyitibwa proopiomelanocortin (POMC), nga okukola kwabwo kuleeta obubonero bw’okukkuta. Okuyita mu nkola zino, GLP-1 enyigiriza bulungi okwagala okulya, ekivaako abalwadde okukendeeza ku mmere gye balya. Mu kugezesebwa mu malwaliro, abalwadde abagejjulukuka oba abagejjulukuka abakozesa GLP-1 baategeeza nti baagala okulya bakendedde n’emmere gye balya ne bakendeera, ekyateekawo omusingi gw’okugejja.
Okwongera ku nsaasaanya y’amaanyi
Ng’oggyeeko okuziyiza okwagala okulya, GLP-1 era eyinza okukwata ku nkyukakyuka y’amasoboza, okwongera ku nsaasaanya y’amaanyi. Okunoonyereza kulaga nti GLP-1 eyinza okwongera ku nsaasaanya y’amaanyi ng’etereeza emirimu gy’ebitundu by’amasavu ebya kitaka. Brown adipose tissue kika kya masavu eky’enjawulo nga omulimu gwayo omukulu kwe kukozesa amaanyi okuyita mu thermogenesis. GLP-1 eyinza okukola amakubo agamu agalaga obubonero mu bitundu by’amasavu ebya kitaka, okutumbula okuwunyiriza kwa asidi w’amasavu n’okutondebwa kw’ebbugumu. Okugatta ku ekyo, GLP-1 eyinza okukosa enkyukakyuka y’amasoboza mu bitundu by’omubiri ng’ebinywa, okwongera ku nsaasaanya y’amasoboza ne mu kuwummula. Okugeza, mu kugezesa ebisolo, oluvannyuma lw’okuweebwa GLP-1, emiwendo gy’amasoboza g’ebisolo gyeyongera, era obuzito bw’omubiri gwabyo bwakendeera ne bwe kiba nti emmere gye baali balya yasigala nga bwe yali, ekiraga nti GLP-1 ekola kinene mu kuddukanya obuzito ng’eyongera ku nsaasaanya y’amaanyi.
Okulungamya enkyukakyuka y’amasavu
GLP-1 era erina ekikolwa eky’okulungamya ku nkyukakyuka y’amasavu. Kiyinza okutumbula okumenya amasavu, okukendeeza ku kukola amasavu, n’okuziyiza okutereka amasavu. Mu kibumba, GLP-1 eyinza okuziyiza enkola y’enziyiza nga fatty acid synthase, bwe kityo n’ekendeeza ku kukola asidi w’amasavu. Okugatta ku ekyo, mu bitundu by’amasavu, GLP-1 eyinza okutumbula okumenya amasavu, okwongera okufulumya asidi z’amasavu ez’obwereere, n’okukwanguyiza okuyingira kwazo mu mitochondria okumenyaamenya okw’okwokya, bwe kityo n’ekendeeza ku kutereka amasavu. Okunoonyereza kulaga nti oluvannyuma lw’ekiseera nga bajjanjabwa ne GLP-1, amasavu mu mubiri gw’abalwadde naddala mu bitundu by’omubiri (visceral fat) gakendeera. Kino tekikoma ku kuyamba mu kugejja wabula era kirina kinene kye kikola ku kulongoosa obulwadde bw’enkyukakyuka y’emmere n’okukendeeza ku bulabe bw’endwadde z’emisuwa.
Okukozesa GLP-1 mu kuddukanya obuzito
Ku balwadde abagejjulukuka oba abagejjulukuka nga bawerekerwako endwadde ezikwatagana nabyo
GLP-1 erina omuwendo gw’abantu gwe gugendereddwamu mu ngeri entegeerekeka ey’okuddukanya obuzito. Ku balwadde abagejjulukuka nga balina BMI ≥30 kg/m² oba abalwadde abagejjulukuka nga balina BMI ≥27 kg/m² era waakiri embeera emu eyeekuusa ku buzito (nga puleesa, enkyukakyuka y’omubiri ey’ekika eky’okubiri, oba hypercholesterolemia), ddagala ddungi eriweweeza ku buzito. Omuddirirwa gwa STEP ogw’okugezesebwa mu malwaliro gwalaga okugejja okw’amaanyi mu balwadde abajjanjabiddwa. Mu kunoonyereza kwa STEP 1, abalwadde abajjanjabwa baatuuka ku kugejja kwa wakati nga 15% mu wiiki 68, ate ekibinja kya placebo kyafiirwa ebitundu nga 2.4% byokka. Ebivudde mu kunoonyereza kuno biraga nti esobola okuyamba abalwadde abagejjulukuka oba abagejjulukuka abalina embeera ezikwatagana okutuuka ku kugejja okw’amaanyi era okw’olubeerera, okulongoosa ebiva mu bulamu, n’okukendeeza ku bulabe bw’endwadde ezeekuusa ku mugejjo.
Nga bigattiddwa wamu n‟okuyingira mu nsonga z‟obulamu
Mu kuddukanya obuzito, GLP-1 etera okukozesebwa ng’egatta wamu n’okuyingira mu bulamu, omuli okukendeeza ku kalori z’olya n’okwongera okukola emirimu gy’omubiri. Singa okugejja kwesigama ku ddagala lyokka nga tekukyusizza mize gya bulamu egitabeera bulungi, ebivaamu bitera obutabeera bya lubeerera. Enkola zombi bwe zigatta zirina ekikolwa eky’okukwatagana: eddagala lino linyigiriza okwagala okulya n’okwongera ku nsaasaanya y’amaanyi, ate okufuga emmere kukendeeza ku kalori z’olya n’okwongera okukola emirimu gy’omubiri kyongera okutumbula ensaasaanya y’amaanyi, ekivaako okugejja okw’amaanyi era okw’olubeerera. Okugeza, mu nkola ezimu ez’obujjanjabi, abalwadde abagoberera enteekateeka y’emmere erimu kalori entono eyakolebwa omukugu mu by’endya ne bongera ku budde bwabwe obw’okukola dduyiro ow’omukka buli wiiki nga bafuna obujjanjabi batuuka ku bivaamu ebirungi ennyo mu kugejja okusinga abo abeesigama ku ddagala oba okuyingira mu bulamu bwokka. Enkola eno ey’okugatta eggumiza obukulu bw’okuddukanya obuzito mu ngeri ey’enjawulo mu kuddukanya obuzito, okuyamba abalwadde okuteekawo obulamu obulungi n’okutuuka ku kufuga obuzito obw’ekiseera ekiwanvu.
Mu bufunzi
GLP-1 eraga obusobozi obw’amaanyi mu kujjanjaba omubiri n’okuddukanya obuzito. Mu bujjanjabi bw’enkyukakyuka mu mubiri, efuga bulungi glucose mu musaayi ng’eyita mu nkola eziwera, etereeza enkola y’obutoffaali bwa β, era esobola okukozesebwa ng’obujjanjabi bumu oba ng’egattibwa wamu n’eddagala eddala eriweweeza ku ssukaali. Mu kuddukanya omugejjo, kiziyiza okwagala okulya, kyongera okusaasaanya amaanyi, n’okutereeza enkola y’amasavu, ekigifuula esaanira abalwadde abagejjulukuka oba abagejjulukuka abalina embeera ezikwatagana nabyo. Bwe kigattibwa wamu n‟okuyingira mu nsonga z‟obulamu, kivaamu ebirungi n‟okusingawo.
Ensonda
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Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
