Glukosa

Lipids are associated with insulin signaling, and ectopic lipidaccumulation is proposed to be the root cause of insulin resistancein liver and muscle (3, 4). Fatty acids are a major class of lipids inmammalian cells, and dysregulation of fatty acid metabolism is akey event responsible for insulin resistance. Acyl-CoA synthetaselong-chain (ACSLs) family proteins are essential enzymes for cellularfatty acid metabolism that catalyze the initial step of acyl-CoAformation from long-chain fatty acids.

Lipid berhubungan dengan sinyal insulin , dan lipid ektopikakumulasi diusulkan menjadi akar penyebab resistensi insulindalam hati dan otot ( 3 , 4 ) . Asam lemak adalah kelas utama lipid disel mamalia , dan disregulasi metabolisme asam lemak adalahperistiwa penting yang bertanggung jawab untuk resistensi insulin . Asil -CoA sintetaserantai panjang ( ACSLs ) protein keluarga enzim penting untuk selulermetabolisme asam lemak yang mengkatalisis langkah awal dari asil -CoAformasi dari asam lemak rantai panjang

Glukosa 1The molecular mechanisms underlying insulin secretion and glucose

metabolism have not been fully elucidated (1–6). Numerous

studies have demonstrated that calcium (Ca2+) plays a pivotal role

in insulin secretion from the islets of Langerhans and that altered

cellular Ca2+ homeostasis may be involved in defective insulin

release (7–11). Nevertheless, according to the classical view of the

glucose-sensing machinery, insulin secretion largely depends on

voltage-activated Ca2+ influx, whereas the role of intracellular Ca2+

release in pancreatic β cells in response to glucose has not been

fully elucidated (12–14). In particular, the mechanistic role of

type 2 ryanodine receptor/Ca2+ release channel (RyR2), which is

expressed on the endoplasmic reticulum (ER) of pancreatic β cells

(14–16), in insulin secretion remains controversial, and a relationship

between RyR2 and type 2 diabetes mellitus (T2DM) has not

been clearly established.

Mekanisme molekuler yang mendasari sekresi insulin dan glukosametabolisme belum dijelaskan secara penuh ( 1-6 ) . banyak sekalipenelitian telah menunjukkan bahwa kalsium ( Ca2 + ) memainkan peran pentingsekresi insulin dari pulau Langerhans dan yang diubahCa2 + seluler homeostasis mungkin terlibat dalam insulin yang rusakrelease ( 11/7 ) . Namun demikian , menurut pandangan klasik darimesin -sensing glukosa , sekresi insulin sangat tergantung padaCa2 + masuknya , sedangkan peran Ca2 intraseluler diaktifkan tegangan - +rilis di sel β pankreas dalam menanggapi glukosa belumsepenuhnya dijelaskan ( 12-14 ) . Secara khusus , peran mekanistiktipe 2 reseptor Ryanodine / Ca2 + channel rilis ( RyR2 ) , yang merupakandiekspresikan pada retikulum endoplasma ( ER ) dari sel β pankreas( 14-16 ) , di sekresi insulin masih kontroversial , dan hubunganantara RyR2 dan diabetes mellitus tipe 2 ( DMT2 ) belumdidirikan jelas .

Pharmacologic stabilization of RyR2 improves insulin secretion

and glucose tolerance. In order to confirm that intracellular

Ca2+ leak via RyR2 leads to decreased insulin secretion, we usedthe Rycal S107, which prevents stress-induced dissociation of

the stabilizing subunit calstabin2 from RyR2, thereby preventing

ER Ca2+ leak (27, 37). S107 is water soluble and has no significant

activity against other ion channels, including human ether-a-gogo–

related gene (HERG) and voltage-gated Ca2+ channels (28).

Stabilisasi farmakologis dari RyR2 meningkatkan sekresi insulindan toleransi glukosa . Untuk mengkonfirmasi intraseluler yangCa2 + kebocoran melalui RyR2 menyebabkan penurunan sekresi insulin , kami usedthe Rycal S107 , yang mencegah stres diinduksi disosiasisubunit calstabin2 menstabilkan dari RyR2 , sehingga mencegahER Ca2 + kebocoran ( 27 , 37 ) . S107 larut dalam air dan tidak memiliki signifikanaktivitas terhadap saluran ion lainnya , termasuk manusia eter -a - gogo-gen terkait ( HERG ) dan tegangan - gated Ca2 + saluran ( 28 ) .