Lymphatic system changes in diabetes mellitus: role of insulin and hyperglycemia

BACKGROUND: Diabetic alterations of blood vessels have been well studied, but much less is known about the lymphatic system, which plays an important role in the transport of particles and defensive responses. Accordingly, we investigated lymphatic changes in diabetic rats. METHODS: Ten, 30 or 60 days after alloxan-induced diabetes (40 mg/kg; i.v.), we studied thoracic duct lymph flow and lymphocyte output, thoracic duct lymph transport of radiotracer particles ((99m)Tc-dextran 500), lymph node uptake and scintigraphic visualization of subcutaneously injected radiotracer particles, as well as the effect of insulin administration and food deprivation. RESULTS: Diabetes significantly increased thoracic duct lymph flow and the transport of dextran from the footpad subcutaneous tissue. Abnormal lymphocyte output from the thoracic duct occurred in the first 10 days. Uptake of dextran into regional lymph nodes was decreased in diabetes. Insulin per se, although not normalizing blood sugar levels, appeared to recover thoracic duct lymphocyte output and lymph node uptake of (99m)Tc-dextran 500 without affecting the thoracic duct lymph flow or the amount of radiotracer recovered therein. Normalization of glycemia (by food deprivation) restored the lymph flow to control levels without modifying the lymphocyte output. On the other hand, under insulin-restored normoglycemic conditions, both the thoracic duct lymph flow and the lymphocyte output were normalized. CONCLUSIONS: These findings suggest that variables related to defensive mechanisms, such as lymphocyte recirculation and particles uptake into the lymph nodes can benefit from insulin treatment, whereas glycemic control can benefit transport mechanisms in the lymphatic system, such as lymph flow and lymphatic transport of particles.