Abstract
Obesity and insulin resistance lead to islet hyperplasia. However, characterization of the associated remodeling of the islet microstructure and neurovascular networks remains a challenge task due to the difficulty of global visualization of the large islet (>200 m) and the neurovascular environment with high definition. Here, we adjusted the pancreatic optical property to examine the islets in the obese young db/db and ob/ob mice via penetrative 3-dimensional (3-D) microscopy. The 3-D images identify the unique “neuro-insular-ductal complex” in the pancreas, featuring the peri- and intra-islet ducts with prominent peri-ductal sympathetic innervation. In vascular characterization, we revealed a decreased population of the ob/ob islet pericytes, which adapt to ensheathing the dilated microvessels with hypertrophic processes. Based on the associated tissue remodeling, we propose a reactive islet microenvironment consisting of the endocrine cells, ductal epithelium, and neurovascular tissues in response to the metabolic challenge that experienced early in life.