Latar belakang: Vitamin B12 merupakan kofaktor enzimmetionin sintase yang berperan padaproses remetilasi homosistein menjadi metionin sehingga, mencegah akumulasi homosistein(hiperhomosisteinemia). Defisiensi vitamin ini dapat menyebabkan terjadinyahiperhomosisteinemia dan memicu stres oksidatif yang menyebabkan resistensi insulin.Penelitian ini bertujuan untuk mengetahui apakah resistensi insulin yang diinduksi restriksivitamin B12 dapat menurunkan kontrol insulin terhadap proses glukoneogenesis melaluipensinyalan FOXO1 dan ekspresi gen targetnya, G6Pc.Metode: Penelitian ini menggunakan 24 jaringan hati tersimpan tikus jantan Spraque-Dawley,berusia 36-40 minggu; yang terbagi dalam 4 kelompok: kelompok kontrol dan kelompokperlakuan yang diberi pakan khusus restriksi vitamin B12 selama 4, 8, dan 12 minggu. Semuasampel jaringan yang digunakan dalam penelitian ini merupakan sampel jaringan yang sama,yang digunakan dalam penelitian oleh Sianipar, dkk, berjudul “Dampak Restriksi Vitamin B12Terhadap Kadar Homosistein, HOMA-IR, dan Gambaran Histopatologi Perlemakan Hati Non-Alkoholik Pada Tikus”. Terhadap 24 sampel jaringan hati tersebut dilakukan pemeriksaanWestern Blot untuk membandingkan aktivitas protein FOXO1 dan pemeriksaan real time-PCRuntuk membandingkan ekspresi gen G6Pc antar kelompok sampel.Hasil: Tidak terdapat perbedaan bermakna, baik aktivitas protein FOXO1 maupun ekspresigen G6Pc antara kelompok restriksi vitamin B12 dengan kelompok kontrol.Kesimpulan: Pada keadaan resistensi insulin yang dipicu oleh hiperhomosisteinemia, padakondisi restriksi vitamin B12, proses glukoneogenesis tergantung insulin melalui inhibisi jalurpensinyalan FOXO1 dan G6Pc tidak berbeda dibandingkan kelompok kontrol. Penelitian lebihlanjut dibutuhkan untuk melihat kemungkinan apakah hiperglikemia pada kondisi ini dapatdisebabkan melalui jalur lain atau adanya penurunan utilisasi glukosa dan proses glikogenesis

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Background: Vitamin B12 is a cofactor of the enzyme methionine synthase which plays a role

in the remetilation process of homocysteine to methionine so as to prevent the accumulation of

homocysteine (hyperhomocysteinemia). Deficiency of this vitamin can cause

hyperhomocysteinemia and trigger oxidative stress which causes insulin resistance. This study

aims to determine whether insulin resistance induced restriction of vitamin B12 can reduce

insulin control of gluconeogenesis through FOXO1 signaling and the expression of its target

gene, G6Pc.

Methods: This study used 24 stored liver tissue of Spraque-Dawley male rats, aged 36-40

weeks; divided into 4 groups: the control group and the treatment group who were given special

food restriction of vitamin B12 for 4, 8, and 12 weeks. All tissue samples used in this study

were the same tissue samples, which were used in a study by Sianipar, et al., titled "The Impact

of Vitamin B12 Restriction on Homocysteine, HOMA-IR, and Histopathological Descriptions

of Non-Alcoholic Fatty Liver in Mice". Western Blot tests were performed on 24 liver tissue

samples to compare FOXO1 protein activity and real time-PCR examination to compare G6Pc

gene expression between sample groups.

Results: There was no significant difference, either the FOXO1 protein activity or G6Pc gene

expression between the vitamin B12 restriction group and the control group.

Conclusion: In a state of insulin resistance triggered by hyperhomocysteinemia, under

conditions of vitamin B12 restriction, gluconeogenesis depends on insulin through the

inhibition of the FOXO1 signaling pathway and G6Pc no different than the control group.

Further research is needed to see the possibility of whether hyperglycemia in this condition can

be caused by other pathways or by a decrease in glucose utilization and the process of

glycogenesis.