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Glitazones are known to exhibit antihyperglycemic activity by decreasing peripheral insulin resistance.
Free fatty acids (FFAs), which can cause peripheral insulin resistance associated with diabetes, induced autophagy in β cells.
In addition to that adiponectin improves hepatic and peripheral insulin resistance, it also presents some anti-inflammatory and hepato-protective activities (Kadowaki et al., 2006).
Consequentially, excess TAG deposition in the liver (hepatic steatosis) and skeletal muscle induces NAFLD and peripheral insulin resistance (Agarwal and Garg, 2006).
A recent study showed that beta-cell specific deficiency of ZnT8 results in low peripheral insulin level but hypersecretion of insulin from pancreas (Tamaki et al., 2013).
TZDs improve peripheral insulin sensitivity.
In summary, these data demonstrate for the first time that HN regulates peripheral insulin action.
STAT3 contributes to the effect of HN on peripheral insulin action [27], [28].
TZDs are insulin sensitising drugs that reduce peripheral insulin resistance and blood glucose levels [28].
Importantly, reductions in peripheral insulin and lipids indicate the target therapeutic window for PIO was reached.
Calorie restriction did not further decrease fasted peripheral insulin levels in GHRKO mice (Figure 1D).
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