Effects of Diabetes on the Transcriptomic Profile of the Endocrine Pancreas: A Systematic Review.

INTRODUCTION: Type 2 Diabetes Mellitus (T2DM) is characterized by progressive pancreatic beta-cell dysfunction and insulin resistance. Although transcriptomic approaches have improved the understanding of molecular mechanisms underlying T2DM, evidence specifically addressing gene expression changes in the endocrine pancreas remains limited and fragmented across experimental and clinical studies. AIM: To systematically review the experimental and clinical evidence on the effects of diabetes on the transcriptomic profile of the endocrine pancreas. METHODS: A comprehensive literature search was conducted in PubMed (MEDLINE), EMBASE, Web of Science, and CINAHL from database inception to December 9, 2024. Data extraction included study design, population, interventions, outcomes, and risk of bias. Two studies met the eligibility criteria. Due to methodological heterogeneity and qualitative outcomes, meta-analysis was not feasible. RESULTS: In Wistar rats fed a high-fat-high-fructose diet, diabetes was associated with downregulation of GCG, INS1, RBP4, PPY, and PYY and upregulation of PDX1, SLC2A2, and INS1 in islet cells. In humans, diabetic individuals showed reduced GPRC5C expression, independent of sex. DISCUSSION: Transcriptomic alterations in the endocrine pancreas have indicated dysfunctions in insulin synthesis, glycemic homeostasis, and β-cell maintenance in type 2 diabetes models. CONCLUSION: Pancreatic beta-cell dysfunction in T2DM may be linked to alterations in the expression of key genes involved in the development, maturation, maintenance, and function of the endocrine pancreas. This review provides insights into the molecular mechanisms of T2DM in pancreatic islets in animal and clinical models and highlights potential candidate biomarkers for future translational research.