Phosphorylation status of fetuin-A is critical for inhibition of insulin action and is correlated with obesity and insulin resistance.

Fetuin-A (Fet-A), a hepatokine associated with insulin resistance, obesity, and incident type 2 diabetes, is shown to exist in both phosphorylated and dephosphorylated forms in circulation. However, studies on fetuin-A phosphorylation status in insulin-resistant conditions and its functional significance are limited. We demonstrate that serum phosphofetuin-A (Ser312) levels were significantly elevated in high-fat diet-induced obese mice, insulin-resistant Zucker diabetic fatty rats, and in individuals with obesity who are insulin resistant. Unlike serum total fetuin-A, serum phosphofetuin-A was associated with body weight, insulin, and markers of insulin resistance. To characterize potential mechanisms, fetuin-A was purified from Hep3B human hepatoma cells. Hep3B Fet-A was phosphorylated (Ser312) and inhibited insulin-stimulated glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Furthermore, single (Ser312Ala) and double (Ser312Ala + Ser120Ala) phosphorylation-defective Fet-A mutants were without effect on glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Together, our studies demonstrate that phosphorylation status of Fet-A (Ser312) is associated with obesity and insulin resistance and raise the possibility that Fet-A phosphorylation may play a role in regulation of insulin action.

How does the robot affect outcomes? A retrospective review of open, laparoscopic, and robotic Heller myotomy for achalasia.

BACKGROUND: Robotic techniques are routinely used in urological and gynecological procedures; however, their role in general surgical procedures is limited. A robotic technique has been successfully adopted for a minimally invasive Heller myotomy procedure for achalasia. This study aims to compare perioperative outcomes following open, laparoscopic, and robotic Heller myotomy. METHODS: This study is a multicenter, retrospective analysis utilizing a large administrative database. The University Health System Consortium (UHC) is an alliance between academic medical centers and affiliate hospitals. The UHC database was accessed using International Classification of Diseases, Ninth Revision, Clinical Modification codes and analyzed. RESULTS: 2,683 patients with achalasia underwent Heller myotomy between October 2007 and June 2011. Myotomy was performed by open surgery (OM) in 418 patients, by laparoscopic approach (LM) in 2,116, and by robotic approach (RM) in 149. Comparison between LM and RM groups demonstrated no significant difference in mortality (0.14 vs. 0.0%; P = 1), morbidity (5.19 vs. 4.02%; P = 0.7), intensive care unit (ICU) admission (6.62 vs. 3.36%; P = 0.12), length of stay (LOS) (2.70 ± 3.87 days vs. 2.42 ± 2.69 days; P = 0.34), or 30-day readmission (1.41 vs. 2.84%; P = 0.27). However, hospital costs were significantly lower for the LM group (US $7,441 ± 7,897 vs. US $9,415 ± 5,515; P = 0.0028). Comparison between OM and RM demonstrated significant lower morbidity (9.08 vs. 4.02%; P = 0.02), ICU admission rate (14.01 vs. 3.36%, P = 0.0002), and LOS (4.42 ± 5.25 days vs. 2.42 ± 2.69 days; P = 0.0001). CONCLUSIONS: The perioperative outcomes are superior in LM and RM groups when compared with OM. The outcomes for the LM and RM group are comparable, with the robotic group having slightly improved results, although with increased costs. We conclude that robotic surgery is equivalent in safety and efficacy to laparoscopic Heller myotomy, and feel that the increased cost should come down as surgeons and manufacturers work together on cost reduction strategies.