Hyperinsulinemia Inhibits Hepatic Peroxisomal β-Oxidation in Rats

Abstract

Studies show that insulin deficiency enhances peroxisomal enzyme activities. It is not known, however, whether hyperinsulinemia exerts the opposite effect on peroxisomes. Male Sprague-Dawley rats were infused with normal saline, glucose or galactose for 7 days. Only glucose caused an increase in serum insulin levels. The increase in insulin secretion, in response to glucose, was blocked with diazoxide. Data show an inverse relationship between serum insulin levels and hepatic peroxisomal beta-oxidation (r2 = 0.90, p < 0.01). While hyperinsulinemic rats had diminished peroxisomal beta-oxidation, lowering serum insulin restored peroxisomal enzyme activity to normal levels. These effects were independent of blood glucose levels (r2 = 0.35). In addition to decreasing peroxisomal beta-oxidation, hyperinsulinemia was accompanied by accelerated animal mortality, an effect which was also prevented by lowering serum insulin levels. Peroxisomal deficit may be a potentially lethal consequence of hyperinsulinemia.

May the force be with you: why resistance training is essential for subjects with type 2 diabetes mellitus without complications

“…Ultimately this can increase ATP production with a higher glucose uptake due to an intensified GLUT4 translocation or lipid oxidation [66]. RT may lead to other adaptations with insulin-mimetics effects: increased fatty acid metabolism (metabolic flexibility) [67] or augmented protein expression of insulin receptors in response to exercise [48].…”

Resistance Training for Diabetes Prevention and Therapy: Experimental Findings and Molecular Mechanisms

“…This transient activation of AMPK could possibly lead to phosphorylation of target proteins involved in a number of metabolic pathways which result in an increase of ATP generating pathways such as glucose uptake via increased GLUT4 translocation and fatty-acid oxidation [80]. Hyperinsulinemia decreases beta-oxidation in insulin resistant subjects and therefore reduces the utilization of fatty acids [81]. The insulin-sensitizing effect of RT releases the brake on beta-oxidation and contributes to improved metabolic flexibility and a more balanced utilization of fatty acids as substrates.…”

The Impact of Peroxisomes on Cellular Aging and Death

“…In rat hepatocytes subjection to conditions of hyperinsulinemia leads to an inhibition of β-oxidation and a concomitant acceleration of aging in these animals (Xu et al, 1995). Clearly, the activity of the peroxisomal marker enzyme catalase decreases by 30–40% in liver samples isolated from old mice and rats (Haining and Legan, 1973; Semsei et al, 1989; Perichon and Bourre, 1995, 1996; Xia et al, 1995).…”