Freshly Baked Bread PowerPoint Templates
Freshly Baked Bread PowerPoint Templates
Diabetes mellitus
faktor-faktor pengatur
homeostasis glukosa.
Dopamine
Tindakan dopamin pada homeostasis glukosa dan
asupan makanan berdampak baik pada sistem saraf
otonom dan sistem endokrin. Aksi sentral yang
berbeda dari sistem dopamin dapat memediasi efek
metaboliknya seperti:
BA: Asam empedu. FXR: farnesoid X reseptor. TGR5: G TGR5 reseptor yang berpasangan protein.
FGF19: faktor pertumbuhan fibroblast-19. GLP1: glukagon seperti peptida 1. Diadaptasi dari Sonne, et al.
2014 49
Amilin
Peran fisiologis amylin. islet amyloid polypeptide (IAPP)
memiliki endokrin serta auto- / parakrin efek. Hal Ini
melibatkan perlambatan dalam pengosongan lambung dan
mengurangi asupan makanan, dengan efek di otak dan di
perut, sehingga mengakibatkan berkurangnya berat badan.
Untuk itu, amylin juga bekerja secara sinergis dengan
hormon-hormon lain seperti leptin. Karena kesamaan
dengan peptida terkait gen kalsitonin, itu juga
mempengaruhi metabolisme tulang dengan menurunkan
aktivitas osteoklas. Selain itu, amylin memengaruhi
vasodilatasi dan sistem renin-angiotensinsin. Efek otokrin
Amylin pada sel β pankreas masih kontroversial. Seperti
mengurangi pelepasan glukagon. Namun, sekresi insulin
yang menurun tidak berubah
Mekanisme Kerja Biguanida
Mekanisme Kerja Biguanida
(1) Serapan metformin menjadi hepatosit dikatalisis oleh transporter kation organik-1 (OCT1). Menjadi
bermuatan positif, obat menumpuk di sel dan, selanjutnya, di mitokondria karena potensi membran
melintasi membran plasma dan membran dalam mitokondria .
(2) Metformin menghambat Kompleks I, mencegah produksi ATP mitokondria dan, dengan demikian,
meningkatkan ADP sitoplasma: ATP dan AMP: rasio ATP (yang terakhir dengan perpindahan dari reaksi
adenilat kinase); perubahan ini mengaktifkan AMPK .
(3) Sebagai alternatif, AMPK dapat diaktifkan oleh mekanisme lysosomal, tetapi membutuhkan Axin dan
adaptor endosomal / lisosom akhir, aktivator MAPK dan mTOR 1 (LAMTOR1) .
(4) Peningkatan rasio AMP: ATP juga menghambat fruktosa-1,6-bifosfatase (FBPase), menghasilkan
penghambatan akut glukoneogenesis , sementara terjadi penghambatan adenilat siklase dan
menurunkan produksi cAMP.
(5) AMPK yang diaktifkan memfosforilasi ACC1 dan ACC2 isoform dari ACC, menghambat sintesis lemak
dan mempromosikan lemak oksidasi sebagai gantinya, sehingga mengurangi simpanan lemak hati dan
meningkatkan sensitivitas insulin hati.
Mekanisme Kerja Biguanida
(6) AMPK juga memfosforilasi dan mengaktifkan spesifik cAMP 3 ′, 5′-siklik fosfodiesterase 4B (PDE4B),
dengan demikian menurunkan cAMP dengan mekanisme lain.
(7) Peningkatan cAMP yang diinduksi glukagon mengaktifkan protein kinase A (PKA) yang tergantung cAMP,
menyebabkan beralih dari glikolisis ke glukoneogenesis melalui fosforilasi dan inaktivasi PFKFB1,
menyebabkan penurunan fruktosa-2,6- bisphosphate (F2,6BP), aktivator alosterik fosfofruktokinase (PFK) dan
inhibitor fruktosa-1,6-bifosfatase (FBPase).
(8) PKA juga memfosforilasi dan menonaktifkan isoform hati glikolitik Enzim piruvat kinase (Pyr K)
(9) memfosforilasi transkripsi factor cAMP response element binding protein (CREB), sehingga menginduksi
transkripsi gen yang mengkode enzim glukoneogenik PEPCK dan G6Pase.
(10) Fosforilasi coactivator transkripsional-2 yang diatur CREB oleh AMPK, atau oleh kinase terkait AMPK
seperti salt-inducible kinase 2 (SIK2), menyebabkan CRTC2 ditahan dalam sitoplasma, mengganggu efek PKA
pada transkripsi PEPCK dan G6Pase . PKA menghambat SIK2 dengan fosforilasi langsung pada banyak situs.
Ac-CoA, asetil-CoA; BPG, 1,3-bisphosphoglycerate; DHAP, dihydroxyacetone phosphate; FBP, fruktosa 1,6-bifosfat; F6P,
fruktosa 6-fosfat; G3P, gliseraldehida 3-fosfat; G6P, glukosa 6-fosfat; Ma-CoA, malonyl-CoA; OAA, oksaloasetat; PEP,
fosfoenolpiruvat; 3PG, 3-fosfogliserat
Mekanisme Kerja Biguanida
Mekanisme Kerja Sulfonilurea
Metabolisme glukosa, yang menghabiskan simpanan ATP, atau pengikatan nateglinide atau repaglinide ke
lokasi pada reseptor sulfonilurea, menyebabkan penutupan saluran kalium ATP-sensitif dan depolarisasi
membran plasma. Masuknya ion kalsium selanjutnya menghasilkan sekresi insulin.
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