Abstract: Objective To study the changes in diaphragmatic function and gene expressions of calcium regulatory proteins in
diabetic rats and explore the mechanism of diaphragm dysfunction in diabetes mellitus. Methods SD rats were randomly
divided into normal control group and diabetic (induced by intraperitoneal STZ injection) group. After 4 and 8 weeks, the
body weight and diaphragm to body weight ratio were measured, and the activities of succinic dehydrogenase (SDH) in the
diaphragm and blood glucose were assayed. The diaphragm contractility was assessed and the alterations of diaphragm
ultrastructure were observed. RT-PCR was used to detect the changes in sarcoplasmic reticulum Ca2 +-ATPase (SERCA) and
phospholamban (PLB) mRNA expressions in the diaphragm. Results The diabetic rats showed a significant weight loss with a
lowered diaphragm to body weight ratio (P<0.01) and SDH activity (P<0.01). The peak twitch tension and maximum tetanic
tension of the diaphragm were significantly lowered and the time to peak contraction and half relaxation time significantly
prolonged (P<0.01) in the diabetic rats, which also exhibited a lowered tetanic force in response to stimulus (P<0.01).
Transmission electron microscopy revealed obvious ultrastructural changes of the diaphragm in diabetic rats. RT-PCR showed
significantly decreased SERCA and increased PLB mRNA expressions in diabetic rat diaphragm (P<0.01), and these changes
intensified with time (P<0.01). Conclusions Diabetes can cause impairment of diaphragmatic ultrastructure, mitochondrial
injuries, and lowered SDH activity and ATP production. Decreased SERCA and increased PLB mRNA expressions in diabetes
result in reduced Ca2+ uptake by the diaphragm sarcoplasmic reticulum to induce diaphragm dysfunction.