Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, - plays anti-inflammatory role in
atherosclerosis, and has
surfactant-releasing effects in lungs.
GLP-1 analogues are used in diabetes
therapy. This is the first study to investigate the effects of
exendin-4, a
GLP-1 receptor agonist, on
lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only
citrate buffer, the second group was given only
exendin-4, the third group was given only
streptozotocin (STZ), and the fourth group was given both
exendin-4 and STZ.
Exendin-4 (3μg/kg) was administered daily by
subcutaneous injection for 30days after mice were rendered diabetic with a single dose of STZ (200mg/kg). Structural alterations, oxidative stress, apoptosis,
insulin signaling and expressions of prosurfactant-C, alpha-smooth muscle actin,
collagen-I and
fibronectin were evaluated in lung tissue. Diabetic mice lungs were characterized by induced oxidative stress, apoptosis,
edema, and cell proliferation. They had honeycomb-like alveoli, thicker alveolar walls, and hypertrophic pneumocytes. Although
exendin-4 treatment improved
pulmonary edema, apoptosis, oxidative stress, and
lung injury, it led to the disrupted
insulin signaling and interstitial
collagen accumulation in the lungs of diabetic mice.
Exendin-4 ameliorates
hyperglycemia-mediated lung damage by reducing
glucose, -oxidative stress and stimulating cell proliferation. However,
exendin-4 led to increased
lung injury partly by reducing
insulin signaling - and
collagen accumulation around pulmonary vasculature in diabetic mice.