Pancreatic pVHL Overexpression via Adenoviral Vector Lowers Blood Glucose in Diet-Induced Type 2 Diabetes Mice

Type 2 Diabetes Mellitus (T2DM) is a chronic, progressive metabolic disorder characterized by persistent high blood glucose levels, peripheral insulin resistance, and impaired glucose tolerance. Its global prevalence is rapidly increasing, posing a significant public health challenge. A central feature of T2DM progression is the dysfunction and eventual loss of pancreatic β-cells, which are exclusively responsible for insulin production in adults. Current therapeutic strategies often manage symptoms but struggle to restore or regenerate β-cell mass and function. The pancreatic islets, where β-cells reside, are highly vascularized endocrine tissues. Their blood supply and crucial metabolic pathways, including glycolysis, are significantly regulated by the VHL–HIF-1α axis, primarily through VEGF. Investigating novel ways to modulate this axis within the pancreas represents a promising, yet underexplored, avenue to improve β-cell health and systemic glucose homeostasis in T2DM.