Abstract
The skeletal muscle is the largest organ in the body. It plays a particularly pivotal role in glucose homeostasis, as it can account for up to 40% of the body and for up to 80%–90% of insulin-stimulated glucose disposal. Hence, insulin resistance (IR) in skeletal muscle has been a focus of much research and review. The fact that skeletal muscle IR precedes β-cell dysfunction makes it an ideal target for countering the diabetes epidemic. It is generally accepted that the accumulation of lipids in the skeletal muscle, due to dietary lipid oversupply, is closely linked with IR. Our understanding of this link between intramyocellular lipids (IMCL) and glycemic control has changed over the years. Initially, skeletal muscle IR was related to total IMCL. The inconsistencies in this explanation led to the discovery that particular lipid intermediates are more important than total IMCL. The two most commonly cited lipid intermediates for causing skeletal muscle IR are ceramides and diacylglycerol (DAG) in IMCL. Still, not all cases of IR and dysfunction in glycemic control have shown an increase in either or both of these lipids. In this review, we will summarise the latest research results that, using the lipidomics approach, have elucidated DAG and ceramide species that are involved in skeletal muscle IR in animal models and human subjects.
Highlights
CSIRO Health and Biosecurity, Kintore Avenue, Adelaide 5000, SA, Australia; Division of Livestock and Farming Systems, South Australian Research and Development Institute
The expanding use of lipidomics will most likely establish which DAG species are responsible for generating the protein kinase C (PKC) isoform/s that is vitally linked with insulin resistance (IR) in in vivo human clinical settings, and pave the way for pharmacological interventions that will arrest the progression of DAG-induced skeletal muscle IR to Type 2 Diabetes Mellitus (T2DM)
Different glycemic control outcomes for people with high intramyocellular lipids (IMCL) content led to the realisation that particular lipid intermediates (DAG and ceramide), rather than total IMCL, was what is important with respect to the genesis of IR
Summary
Since the Banting group’s discovery of insulin, substantial progress has been made in elucidating the insulin signalling pathways (Figure 1). Since its first description by Aitman et al [25], CD36 is the most commonly studied fatty acid carrier in skeletal muscle It is located within the cytosol of myocytes and moves back and forth to the plasma membrane (PM) to enable the movement of FFA from plasma into muscle cells; a pattern that mirrors the role of GLUT4 in glucose uptake. It is not yet known whether the regulation (control switch) of which protein carrier translocates to PM to facilitate glucose and/or FFA uptake by the skeletal muscle is driven systemically or at the myocyte level This is one of the critical control points that needs to be elucidated if we are to fully unravel the basis of skeletal muscle fuel selection and its contribution to insulin resistance and T2DM. We will summarise the evolving evidence linking different aspects of IMCL with IR
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
