(PTFS07-01-26) Hyperglycemia Reshapes Intestinal Structure and Function in Diabetes

Objectives: Diabetes is a metabolic disorder characterized by chronically high blood glucose levels (hyperglycemia). Chronic hyperglycemia is known to cause long-term damage and dysfunction in multiple organs, including the intestine. This study aims to determine the effects of hyperglycemia on gut structure and function using a diabetic mouse model.

Methods: We employed a streptozotocin (STZ)-induced diabetic mouse model, in which STZ selectively damages pancreatic β-cells, leading to reduced insulin production and sustained hyperglycemia. Using this model, we examined how hyperglycemia affects intestinal morphology, nutrient absorption, and transit, and further assessed how these changes correlate with blood glucose levels.

Results: Diabetes caused fecal retention in the intestine, accompanied by decreased intestinal transit. Structurally, diabetic mice exhibited increased intestinal weight and elongated villi and crypts in both the small and large intestines. These morphological changes were associated with elevated epithelial cell proliferation (Proliferating Cell Nuclear Antigen, PCNA, expression) and increased fibrosis, as evidenced by Sirius Red staining and α-smooth muscle actin (α-SMA) expression. Functionally, hyperglycemia altered nutrient absorption pathways, leading to increased expression of glucose transporters and decreased expression of fat transporters. Reduced fat absorption in diabetic mice was further supported by elevated fecal triglyceride content and impaired fat absorption in functional assays. Additionally, increases in colon weight and decreases in intestinal transit were positively correlated with blood glucose levels.

Conclusions: Our findings demonstrate that chronic hyperglycemia significantly alters intestinal structure, promotes epithelial proliferation and fibrosis, and disrupts normal nutrient absorption and transit. These results highlight the intestine as an important and underrecognized target organ affected by diabetes and may provide insight into gastrointestinal complications commonly observed in diabetic patients.

Funding Sources: This work was supported by the National Heart, Lung, and Blood Institute grant HL168465.