Uji Translokasi GLUT4 Pada Sel Otot Sehat Dan Hiperinsulinemia Terhadap Ekspresi Protein PDK1 Dengan Blocker PKCζ

Deviana, Tania Puspa Bela (2026) Uji Translokasi GLUT4 Pada Sel Otot Sehat Dan Hiperinsulinemia Terhadap Ekspresi Protein PDK1 Dengan Blocker PKCζ. Other thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Diabetes Melitus Tipe 2 (DMT2) merupakan gangguan metabolik yang ditandai dengan hiperglikemia kronis akibat kegagalan uptake glukosa oleh sel target, termasuk sel otot rangka. DMT2 berkaitan dengan kondisi hiperinsulinemia yang menyebabkan gangguan pada jalur persinyalan insulin. Pada kondisi hiperinsulinemia terjadi redistribusi sinyal antara PDK1, Serine/Threonine Kinase atau Protein Kinase B (AKT), dan Protein Kinase C zeta (PKCζ) yang menyebabkan aktivasi PKCζ secara berlebih. Aktivasi PKCζ yang berlebih pada kondisi hiperinsulinemia dapat menghambat translokasi GLUT4 (Glucose Transporter Type 4) sehingga glukosa tidak masuk secara optimal ke sel otot. Penelitian ini dilakukan melalui uji in vitro menggunakan Human Skeletal Muscle Cells. Kondisi hiperinsulinemia dimodelkan melalui paparan glukosa konsentrasi tinggi (25 mM) selama 6 hari, sedangkan kondisi sel normal dipaparkan glukosa normal (5 mM). Selanjutnya diberikan blocker PKCζ dalam dua kondisi perlakuan. Konsentrasi PDK1, AKT, dan GLUT4 diukur dengan metode Enzyme-Linked Immunosorbent Assay (ELISA) dengan waktu pengamatan 10, 20, 30, 40, dan 50 menit. Hasil menunjukkan bahwa konsentrasi PDK1, AKT, dan GLUT4 berfluktuasi pada setiap perlakuan. Pola konsentrasi yang sama terlihat pada akhir pengamatan. Konsentrasi PDK1 meningkat pada kondisi normal tanpa blocker PKCζ dan pada hiperinsulinemia dengan blocker PKCζ, sedangkan konsentrasi PDK1 menurun pada kondisi normal dengan blocker dan hiperinsulinemia tanpa blocker. Pola konsentrasi AKT sebagian besar sejalan dengan PDK1, sedangkan pola konsentrasi GLUT4 sebagian besar sejalan dengan AKT. Hal tersebut menunjukkan sinyal insulin masih dapat diteruskan pada PDK1-AKT-GLUT4. Secara keseluruhan, penghambatan PKCζ berpotensi mempertahankan persinyalan insulin pada kondisi hiperinsulinemia, sedangkan pada kondisi normal penghambatan PKCζ menyebabkan penurunan efisiensi persinyalan insulin
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Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia resulting from impaired glucose uptake by target cells, including skeletal muscle cells. T2DM is associated with hyperinsulinemia, which disrupts the insulin signaling pathway. Under hyperinsulinemic conditions, signal redistribution occurs among 3-Phosphoinositide-Dependent Protein Kinase-1 (PDK1), Serine/Threonine Kinase or Protein Kinase B (AKT), and Protein Kinase C zeta (PKCζ), leading to excessive PKCζ activation. Excessive PKCζ activation under hyperinsulinemic conditions may inhibit the translocation of Glucose Transporter Type 4 (GLUT4), thereby reducing glucose uptake into skeletal muscle cells. This study was conducted through an in vitro assay using Human Skeletal Muscle Cells. Hyperinsulinemic conditions were modeled by exposing cells to a high glucose concentration (25 mM) for six days, whereas normal cells were exposed to a normal glucose concentration (5 mM). Subsequently, a PKCζ blocker was administered under both treatment conditions. The concentrations of PDK1, AKT, and GLUT4 were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) at 10, 20, 30, 40, and 50 minutes. The results showed that the concentrations of PDK1, AKT, and GLUT4 fluctuated across all treatments. Similar concentration patterns were observed at the end of the observation period. PDK1 concentration increased under normal conditions without the PKCζ blocker and under hyperinsulinemic conditions with the PKCζ blocker, whereas it decreased under normal conditions with the blocker and under hyperinsulinemic conditions without the blocker. The AKT concentration pattern was generally consistent with that of PDK1, whereas the GLUT4 concentration pattern was generally consistent with that of AKT, indicating that insulin signaling was maintained through the PDK1–AKT–GLUT4 pathway. Overall, PKCζ inhibition may preserve insulin signaling under hyperinsulinemic conditions, whereas under normal conditions, PKCζ inhibition reduces insulin signaling efficiency.

Item Type:	Thesis (Other)
Uncontrolled Keywords:	AKT, GLUT4, Hiperinsulinemia, PDK1, PKCζ, AKT, GLUT4, Hyperinsulinemia, PDK1, PKCζ
Subjects:	Q Science > QP Physiology > QP624 Molecular biology.
Divisions:	Faculty of Science and Data Analytics (SCIENTICS) > Biology > 46201-(S1) Undergraduate Thesis
Depositing User:	Tania Puspa Bela Deviana
Date Deposited:	24 Jul 2026 01:47
Last Modified:	24 Jul 2026 01:47
URI:	http://repository.its.ac.id/id/eprint/136689

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