Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment

Abstract

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different pathological processes, both result in β-cell destruction and/or dysfunction, which ultimately lead to insufficient β-cell mass to maintain normoglycemia. Therefore, therapeutic agents capable of inducing β-cell proliferation is crucial in treating and reversing diabetes; unfortunately, adult human β-cell proliferation has been shown to be very limited (~0.2% of β-cells/24 h) and poorly responsive to many mitogens. Furthermore, diabetogenic insults result in damage to β cells, making it ever more difficult to induce proliferation. In this review, we discuss β-cell mass/proliferation pathways dysregulated in diabetes and current therapeutic agents studied to induce β-cell proliferation. Furthermore, we discuss possible combination therapies of proliferation agents with immunosuppressants and antioxidative therapy to improve overall long-term outcomes of diabetes.

Antioxidant potential of gotu kola leaf extract (Centella asiatica (L.) Urban) as an alternative to antihyperglycemic herbal drinks

“…Natural antioxidants such as ascorbic acid, carotenoids, tocopherols, phenolic compounds, and flavonoids are safe alternatives to synthetic antioxidants. Flavonoid compounds can counteract free radicals and have biological activities such as inhibiting cancer cells, anti-inflammatory, antiviral, anti-fungal, and antibacterial [6]. Gotu kola is a wild plant that Indonesian people have long consumed as a traditional medicinal herb.…”

Exploring a Synergistic Approach: Dual GLP-1 Agonist Combined with Degludec Basal Insulin for Early Type 1 Diabetes Treatment and its Impact on Albumin-Insulin Producing Cells Expression."

“…[18] This proliferative effect of GLP-1 on beta cells holds significant potential for the development of innovative therapeutic approaches in treating early type 1 diabetes, with the aim of restoring beta cell mass and function. [19] To optimize the pharmacokinetic properties of GLP-1 and extend duration of action, researchers have explored modifications using albumin ligands. [20] Albumin, the most abundant protein in the blood plasma, has a long half-life and can reversibly bind to various drugs and hormones.…”

Aktivitas Antihiperglikemik Ekstrak Etanol Daun Cincau Hitam Pada Mencit Putih Jantan Yang Diinduksi Aloksan

“…Mekanisme berikutnya senyawa fitokimia diduga mampu menurunkan kadar trigliserida dan kandungan kolesterol, yang akan berdampak pada hiperlipidemia, yang merupakan salah satu fitur patofisiologis DM (Lin et al, 2022). Mekanisme lainnya adalah bahwa senyawa bioaktif seperti flavonoid dan alkaloid dapat melindungi terhadap kerusakan sel β, meningkatkan proliferasi dan merangsang sekresi insulin (Eguchi et al, 2022).…”