The impact of glucocorticoids upon the insulin sensitivity of skeletal muscle

Glucocorticoid (GC) excess is characterised by central obesity, hypertension, proximal myopathy, insulin resistance and in some cases overt type 2 diabetes (T2D). However, the precise molecular mechanisms responsible for these observation have not been defined in detail. We have shown that GCs reduce the insulin sensitivity of skeletal muscle by impacting upon the insulin signalling cascade at several critical points: IRS1, PI3K and AS160. Furthermore, we have described a novel role of GC, and GCs with insulin, in the regulation of intramyocellular lipid metabolism, which may underpin GC-induced insulin resistance in this tissue. We have also highlighted the importance of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which controls local GC availability, as a critical regulator of skeletal muscle insulin sensitivity, and have provided new insight into the insulin sensitizing actions of selective 11β-HSD1 inhibitors. In summary, these data highlight the importance of GCs, and pre-receptor GC metabolism in the regulation of lipid metabolic pathways and response to insulin stimulation in skeletal muscle.

Name dc:type.qualificationname

d_ph

Level dc:type.qualificationlevel

d_ph

Grantor dc:publisher.institution

University of Birmingham

Year dc:date.issued

2010

Author dc:creator

• Morgan, Stuart Andrew

• RC Internal medicine
• QP Physiology