Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery.

The Roux-en-Y gastric bypass (RYGB) is a one-of-a-kind treatment among contemporary bariatric surgical procedures, and its therapeutic effects for type 2 diabetes mellitus (T2DM) are satisfactory. The present study performed isobaric tags for relative and absolute quantification (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identifying different proteomics between T2DM rats with or without Roux-en-Y gastric bypass (RYGB) surgery, and GTP binding elongation factor GUF1 (Guf1) was first found to be significantly upregulated in rats from the T2DM plus RYGB group. In the cellular lipotoxicity model induced by palmitic acid stimulation of rat pancreatic beta cell line, INS-1, palmitic acid treatment inhibited cell viability, suppressed GSIS, promoted lipid droplet formation, promoted cell apoptosis, and induced mitochondrial membrane potential loss. The effects of palmitic acid on INS-1 cells mentioned above could be partially eliminated by Guf1 overexpression but aggravated by Guf1 knockdown. Last, under palmitic acid treatment, Guf1 overexpression promotes the PI3K/Akt and NF-κB signaling but inhibits the AMPK activation. Guf1 is upregulated in T2DM rats who received RYGB, and Guf1 overexpression improves cell mitochondrial functions, increases cell proliferation, inhibits cell apoptosis, and promotes cell functions in palmitic acid-treated β cells.