High-Dose Insulin Therapy Reduces Postoperative Liver Dysfunction and Complications in Liver Resection Patients through Reduced Apoptosis and Altered Inflammation

Abstract

The hyperinsulinemic-normoglycemic clamp technique reduced postoperative negative outcomes by suppressing apoptosis. This phenomenon appears to be linked with higher substrate availability and altered cytokine secretion profile and may provide a long-term benefit of this therapy on liver resection patients.

Randomized clinical trial of the impact of insulin therapy on liver function in patients undergoing major liver resection

“…These patients had significantly lower intraoperative blood glucose levels, and experienced fewer fluctuations, with no incidence of severe hypoglycaemia. A subgroup analysis of the present study (reported separately) found an antiapoptotic effect of insulin therapy on hepatocytes and a decrease in systemic inflammation, in agreement with other studies, .…”

“…In a previous study insulin was shown to improve survival of wild‐type neonatal hepatocytes by preventing caspase‐3 activation, proapoptotic gene expression and DNA laddering. As insulin is a potent anti‐inflammatory agent it may have regulated the perioperative inflammatory response caused by surgery, liver manipulation and resection, , . Further studies are needed to distinguish the benefit of each component of this metabolic support protocol.…”

Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice

“…However, as we have demonstrated here, Fgf15 also exhibits a direct mitogenic action on liver cells which is not displayed by insulin 5 8. Therefore, it would be very interesting to examine the therapeutic value of FGF19 administration to patients undergoing liver resection, either alone as recently tested with insulin53 or in combination with the pancreatic hormone. Moreover, our findings also suggest that synthetic compounds that strongly activate FXR, and in turn can upregulate the expression of FGF19,34 54 could be useful to potentiate liver regeneration in patients with cholestasis undergoing major liver surgery.…”

Co-administration of erythropoietin and iron complex improves late-phase liver regeneration

“…Based on the understanding of mechanisms of liver regeneration, several successful strategies have been developed to counteract post-operative liver insufficiency or post-hepatectomy liver failure (15)(16)(17). Despite successful hepatectomy, insufficient remnant liver volume and function are central factors in the etiology of fulminant liver failure after major liver resection (18).…”