Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.

BACKGROUND AND AIMS: A diminution in skeletal muscle mitochondrial function due to ectopic lipid accumulation and excess nutrient intake is thought to contribute to insulin resistance and the development of type 2 diabetes. However, the functional integrity of mitochondria in insulin-resistant skeletal muscle remains highly controversial. METHODS: 19 healthy adults (age:28.4 ±â€¯1.7 years; BMI:22.7 ±â€¯0.3 kg/m2) received an overnight intravenous infusion of lipid (20% Intralipid) or saline followed by a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity using a randomized crossover design. Skeletal muscle biopsies were obtained after the overnight lipid infusion to evaluate activation of mitochondrial dynamics proteins, ex-vivo mitochondrial membrane potential, ex-vivo oxidative phosphorylation and electron transfer capacity, and mitochondrial ultrastructure. RESULTS: Overnight lipid infusion increased dynamin related protein 1 (DRP1) phosphorylation at serine 616 and PTEN-induced kinase 1 (PINK1) expression (P = 0.003 and P = 0.008, respectively) in skeletal muscle while reducing mitochondrial membrane potential (P = 0.042). The lipid infusion also increased mitochondrial-associated lipid droplet formation (P = 0.011), the number of dilated cristae, and the presence of autophagic vesicles without altering mitochondrial number or respiratory capacity. Additionally, lipid infusion suppressed peripheral glucose disposal (P = 0.004) and hepatic insulin sensitivity (P = 0.014). CONCLUSIONS: These findings indicate that activation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. Targeting mitochondrial dynamics and quality control represents a promising new pharmacological approach for treating insulin resistance and type 2 diabetes. CLINICAL TRIAL REGISTRATION: NCT02697201, ClinicalTrials.gov.

Comparison of heat generated by alumina-toughened zirconia and stainless steel burs for implant placement.

PURPOSE: In current practice, two types of burs are typically used: stainless steel (SS) and alumina-toughened zirconia (ATZ). The present study evaluated the durability of these two burs in relation to osteotomy creation for implant placement. In addition, the effects of the two types of burs on a bone model were examined. MATERIALS AND METHODS: SS and ATZ burs were compared under controlled conditions in a swine rib osteotomy. The heat generated and time necessary for perforation were measured and analyzed with repeated-measures one-way analysis of variance. The burs and bone samples were evaluated using scanning electron microscopy. RESULTS: New ATZ and SS burs showed greater bone disruption compared to burs that had been used 80 times. Brand new burs of either material showed small manufacturing defects, which increased in number with use. No clinically or statistically significant differences were found between burs with respect to temperature and time for perforation. CONCLUSIONS: SS and ATZ burs can be used several times for implant site preparation under controlled conditions without reaching a temperature that is harmful to the bone. Both burs wear under repeated use, but not to an excessive degree. The duller burs produced smoother perforations than did the new ones.