Description:
<jats:sec><jats:title>Background</jats:title><jats:p>Sirtuin‐1 (SIRT1) through its deacetylase activity, is involved in numerous cellular processes including metabolism, gene silencing, and cellular survival. Recently, SIRT1 has been shown to play an important role in glucose metabolism and glucose tolerance, in part through its effect on insulin secretion and peripheral insulin sensitivity. Less is known about the exact tissue location for SIRT1's primary role in regulating blood glucose. In addition, little is known about the role SIRT1 may play in regulating blood glucose following the induction of an obese phenotype. We hypothesized that global over‐expression of the SIRT1 gene, as compared to lack of expression in metabolically active tissue, would allow for efficacious and enhanced glucose tolerance following hyperglycemic insult in both lean and obese animals.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Thirty‐two 60–70‐week‐old male and female (C57 Bl‐6) mice were used in the study. Groups were as follows: wild type (WT; N=10), SIRT1 global over‐expressors (OE; N=11), SIRT1 skeletal muscle satellite cell knockout (SKO; N=5), and SIRT1 skeletal muscle cell knockout (MKO; N=6). All groups underwent a glucose tolerance test (GTT) by administering an intraperitoneal injection of glucose solution containing 1g/kg of glucose relative to bodyweight following an eight hour fast. The resulting blood glucose levels were measured using tail stick and a standard Bayer™ Contour<jats:sup>®</jats:sup> glucometer at baseline, and 15, 30, 60, 90, and 120 minutes post‐injection. Following a 10‐week high caloric feeding regimen, which resulted in significant weight gain, WT and OE mice were given a second GTT. Data were analyzed using a one‐way and two‐way ANOVA with STATVIEW with significance set at 0.05.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>All measurements were determined to be independent of gender and weight. Initial fasting glucose levels were similar across all groups. Peak blood glucose was significantly lower in SKO (148±22 mg/dL) versus WT (207±21 mg/dL), OE (230 ± 10 mg/dl) and MKO (202 ± 12 mg/dl). The area under the glucose tolerance curves (AUC) was also significantly lower in SKO (652) versus WT (868), OE (895), and MKO (833). There was a significant interaction pre‐to‐post obesity between WT vs OE for AUC (WT‐pre: 868, WT‐post: 1108; OE‐pre: 895, OE‐post: 807).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Skeletal muscle satellite cell knockout of SIRT1 appeared to result in a better handling of glucose following IPGTT. Following 10 weeks of increased calorie consumption, resulting in significant weight gain, the OE group actually appeared to handle glucose better than WT litter‐mates.</jats:p><jats:p><jats:bold>Support or Funding Information</jats:bold></jats:p><jats:p>This project has been funded through grants from WV‐INBRE (NIH grant P20 GM103434) to the Genomics Core Facility and the WV Program to Stimulate Competitive Research (PSCoR)</jats:p><jats:p>This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in <jats:italic>The FASEB Journal</jats:italic>.</jats:p></jats:sec>