The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes

OBJECTIVE-Our previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes. The objective was to determine whether SNAP23 may also be involved in the known association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23. RESEARCH DESIGN AND METHODS-We analyzed skeletal muscle biopsies from patients with type 2 diabetes and healthy, insulin-sensitive control subjects for expression (mRNA and protein) and intracellular localization (subcellular fractionation and immunohistochemistry) of SNAP23, and for expression of proteins known to interact with SNARE proteins. Insulin resistance was determined by a euglycemic hyperinsulinemic clamp Potential mechanisms for regulation of SNAP23 were also investigated in the skeletal muscle cell line L6. RESULTS-We showed increased SNAP23 levels in skeletal muscle from patients with type 2 diabetes compared with that from lean control subjects Moreover, SNAP23 was redistributed from the plasma membrane to the microsomal/cytosolic compartment in the patients with the type 2 diabetes Expression of the SNARE-interacting protein Munc18c was higher in skeletal muscle from patients with type 2 diabetes Studies in L6 cells showed that Munc18c promoted the expression of SNAP23. CONCLUSIONS-We have translated our previous in vitro results into humans by showing that there is a change in the distribution of SNAP23 to the interior of the cell in skeletal muscle from patients with type 2 diabetes. We also showed that Munc18c is a potential regulator of SNAP23. Diabetes 59: 1870-1878, 201

Load-relief of walking aids on osseointegrated fixation: instrument for evidence-based practice

Clinicians are currently in demand of tools enabling individual assessment during their daily practice of load-relief of walking aids. The first aim of this article is to describe a portable kinetic system that could be used to measure directly the true load applied on the residuum during assisted walking. The second aim is to present the information that can be derived from the raw loading data. The third aim is to provide an example for a participant. One active transfemoral amputee fitted with an osseointegrated fixation was asked to walk in straight level line with no aid, one stick, one and two elbow crutches on a 20 m walkway. The load-relief was measured using a six-channel transducer and recorded using a data logger. The overall loading was decreased by 2% using one stick, 5% using one crutch and by 10% using two crutches. This study presents a method that can be used by clinicians facing the challenge of prescribing and assessing walking aids to restore the locomotion of lower limb amputees in the framework of an evidence-based practice. © 2006 IEEE