Effect of Duodenal-Jejunal Bypass on Skeletal Muscle Insulin Signaling in Goto-Kakizaki Rats

Abstract

Gastric bypass surgery (RYGBP) for the treatment of obesity has proven to clinically reverse type 2 diabetes mellitus. RYGBP involves both gastric reduction and bypass of the proximal small intestine. Duodenal-Jejunal Bypass (DJB) is a surgical procedure that bypasses the proximal small intestine without gastric reduction and has been shown to improve oral glucose tolerance in Goto-Kakizaki (GK) rats, a non-obese animal model of T2DM. We hypothesized that DJB may improve oral glucose tolerance in GK rats by improving insulin signaling in skeletal muscle, the main depot for insulin stimulated glucose uptake. DJB was performed on male 10-12 week old GK rats (GK-DJB), and sham operations were performed on GK rats (GK-Sham). Insulin stimulated IRS-1, phospho-serine 307 of IRS-1, Akt, and phospho-Akt were determined using Western blot. Phospho-Akt was significantly higher in GK-DJB when compared to GK-Sham in soleus and tended to be higher in gastrocnemius (p=0.107). Akt was significantly higher in GK-DJB when compared to GK-Sham in gastrocnemius and tended to be higher in soleus (p=0.074). Phospho-serine 307 of IRS-1 and total IRS-1 were not different between GK-DJB and GK-Sham in gastrocnemius. In conclusion, bypassing the proximal small intestine (DJB) improves components of skeletal muscle insulin signaling in GK rats, providing mechanistic evidence for the improvement in oral glucose tolerance associated with DJB.