Advancing diabetes management: Exploring pancreatic beta-cell restoration's potential and challenges

Abstract

Diabetes mellitus, characterized by chronic hyperglycemia due to insulin deficiency or resistance, poses a significant global health burden. Central to its pathogenesis is the dysfunction or loss of pancreatic beta cells, which are res-ponsible for insulin production. Recent advances in beta-cell regeneration research offer promising strategies for diabetes treatment, aiming to restore endogenous insulin production and achieve glycemic control. This review explores the physiological basis of beta-cell function, recent scientific advan-cements, and the challenges in translating these findings into clinical applications. It highlights key developments in stem cell therapy, gene editing technologies, and the identification of novel regenerative molecules. Despite the potential, the field faces hurdles such as ensuring the safety and long-term efficacy of regen-erative therapies, ethical concerns around stem cell use, and the complexity of beta-cell differentiation and integration. The review highlights the importance of interdisciplinary collaboration, increased funding, the need for patient-centered approaches and the integration of new treatments into comprehensive care strategies to overcome these challenges. Through continued research and collaboration, beta-cell regeneration holds the potential to revolutionize diabetes care, turning a chronic condition into a manageable or even curable disease.

Keywords: Beta cell regeneration; Diabetes therapies; Gene editing; Molecular therapeutics; Regenerative medicine; Stem cell therapy.

Figure 1

Overview of beta-cell function and insulin secretion. ATP: Adenosine triphosphate; Ca²⁺: Calcium ion; GLUT-2: Glucose transporter 2; GLUT-4: Glucose transporter 4; K_ATP: Adenosine triphosphate-sensitive potassium channel; TCA cycle: Tricarboxylic acid cycle.

Figure 2

Factors influencing beta-cell function and insulin secretion. The green arrow refers to the promotion of beta-cell proliferation. The red arrow refers to promoting beta-cell apoptosis. The blue arrow indicates stimulation of insulin release. The orange arrow indicates inhibiting insulin secretion. AKT: Protein kinase B; ER: Endoplasmic reticulum; GLP-1: Glucagon-like peptide 1; HGF: Hepatocyte growth factor; IGF-1: Insulin-like growth factor 1; mTOR: Mechanistic target of rapamycin; PI3K: Phosphoinositide 3-kinase.

Figure 3

Overview of regenerative therapies for diabetes treatment. Cas9: CRISPR-associated protein 9; CRISPR: Clustered regularly interspaced short palindromic repeats; EGF: Epidermal growth factor; hESCs: Human embryonic stem cells; GLP-1: Glucagon-like peptide-1; iPSCs: Induced pluripotent stem cells; MSCs: Mesenchymal stem cells; TALENs: Transcription activator-like effector nucleases; ZFNs: Zinc finger nucleases.