1-hydroxymethyl Harmine-TGFβSF Inhibitor: Inovasi Terapi Diabetes Melitus Terbaru Melalui Inisiasi Proses Regenerasi Sel β Pankreas pada Penderita DM Tipe 1 dan 2

Background: Type 1 and 2 diabetes mellitus (DM) is a chronic metabolic disease most commonly affects millions of people worldwide. Despite the differences in pathogenesis, both share one thing in common - that is the drastic depletion in the number of pancreatic β cells. Unfortunately, physiological proliferation of β cells has come to a halt starting from the first year of neonatal. To overcome this problem, researchers have been searching for molecules with the ability to induce β cells proliferation. Upon extensive screening, only harmine was proven to be the most potent β cells proliferation inducer. Furthermore, combination of harmine with TGFβSF inhibitor was found to boost harmine’s effectivity even more. Another development was also made to improve harmine’s selectivity by incorporating 1-hydroxymethyl group. Objective: Evaluate the potency of 1-hydroxymethyl harmine-TGFβSF inhibitor as a novel therapy for DM. Method: A systematic literature study was conducted with the database from Pubmed, Google Scholar, ScienceDirect, and Proquest for articles published within 2015-2019. Discussion: This literature review yields result that harmine-TGFβSF inhibitor is proven to induce β cells proliferation up to 18%/day or equal to 18 times the normal cell proliferation rate during embryogenesis. Moreover, incorporating 1-hydroxymethyl group into harmine is proven not only to improve selectivity but also lessen the toxicity, making 1-hydroxymethyl harmine safe as a novel therapy for diabetes. Conclusion: 1-hydroxymethyl harmine-TGFβSF inhibitor display promising potential as a novel therapy for all type of diabetes patients. Keywords: diabetes mellitus, harmine, TGFβSF inhibitor, β cell proliferation Latar Belakang: Diabetes Melitus (DM) tipe 1 maupun tipe 2 merupakan penyakit metabolik kronis yang paling banyak ditemukan di seluruh dunia. Walaupun memiliki proses patogenesis yang berbeda, namun kedua tipe DM ini ternyata memiliki kesamaan, yaitu terjadinya penurunan kuantitas sel β pankreas. Sayangnya, kemampuan regenerasi sel β pankreas manusia telah terhenti semenjak tahun pertama masa neonatal. Untuk menangani permasalahan tersebut, para peneliti menemukan sebuah molekul bernama harmine yang terbukti efektif menginisiasi proses regenerasi sel β pankreas. Selanjutnya, untuk meningkatkan efektifitas dari harmine agar lebih baik lagi, peneliti kemudian mengkombinasikan harmine dengan TGFβSF inhibitor. Sedangkan, untuk meningkatkan selektivitas dari harmine,