Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological...

Area of Science:

• Biomedical Engineering
• Metabolic Diseases
• Extracellular Matrix Biology

Background:

• Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with severe complications.
• Chronic hyperglycemia in T2DM induces extracellular matrix (ECM) modifications, altering tissue stiffness, fibrosis, inflammation, and angiogenesis.
• Understanding ECM biochemistry and biomechanics in T2DM and obesity is crucial for disease management.

Purpose of the Study:

• To systematically investigate the histological and biomechanical properties of ECM in various tissues affected by T2DM and obesity.
• To compare ECM alterations in obese (ob/ob) and diabetic (db/db) mouse models with control groups.
• To assess the suitability of decellularized matrices as biomimetic scaffolds for in vitro studies.

Main Methods:

• Analysis of native and decellularized skin, kidney, adipose tissue, liver, and heart from 8-week-old ob/ob, db/db, and control (C57BL/6J) mice.
• Histological staining, immunofluorescence, scanning electron microscopy, rheology, and atomic force microscopy were employed.
• Biomechanical testing to determine tissue stiffness (G*).

Main Results:

• Significant architectural differences were observed in ob/ob and db/db tissues compared to controls.
• db/db mice exhibited loose epidermis, altered dermis, glomerulopathy, and severe liver steatosis.
• ECM protein distribution varied, with laminin accumulation in db/db kidneys and decreased hyaluronic acid in hepatocytes of both models. Diabetic adipose tissue was significantly stiffer (G* ≈ 10,000 Pa) than obese or control tissues (G* ≈ 3000-5000 Pa).

Conclusions:

• Diabetes and obesity induce selective and severe histological and biomechanical alterations in various tissue matrices.
• Decellularized ECM matrices retain structural integrity, serving as effective biomimetic scaffolds for 3D in vitro models.
• Altered ECM biomechanics in T2DM and obesity can significantly impact vital physiological processes, including angiogenesis, wound healing, and inflammation.