Suppression of hyperinsulinemia restores growth hormone secretion and metabolism in obese mice.
The well-balanced secretion between insulin and growth hormone (GH) is essential in regulating substrate metabolism, energy metabolism, and body composition. High insulin and low GH levels are often observed in obesity, contributing to reduced energy expenditure and further fat accumulation. Although suppression of hyperinsulinemia is proposed as a treatment for obesity, changes in GH secretion and energy metabolism following this treatment are not thoroughly studied. This leaves unexplained observations, such as unchanged lean mass following insulin reduction. In this study, high-fat diet-induced obese (DIO) and normal chow-fed lean mice on a C57BL/6J background were treated for 7 weeks with diazoxide (1250 mg/kg in food), a KATP channel opener that suppressed insulin secretion. Diazoxide treatment for 10 days was sufficient to increase pulsatile GH secretion in DIO mice before any significant body weight change. The restored insulin-GH balance in DIO mice was followed by improvement in substrate and energy metabolism in a prolonged treatment period (4-6 weeks), including reduced fat mass, increased lipid oxidation and energy expenditure, as well as improved insulin sensitivity and metabolic flexibility. These metabolic benefits occurred along with the changes in the expression level of genes regulated by the insulin-GH balance. When applying diazoxide to normal chow-fed normoinsulinemic lean mice, none of the above metabolic effects was observed, suggesting that the metabolic changes following diazoxide treatment were mediated through the suppression of hyperinsulinemia. These results suggest that suppression of hyperinsulinemia by diazoxide restores GH secretion and improves substrate and energy metabolism in DIO mice.
['Huang|Zhengxiang|Z|0000-0002-1194-2701', 'Lu|Xuehan|X|', 'Huang|Lili|L|', 'Chen|Yang|Y|', 'Zhang|Chunhong|C|', 'Veldhuis|Johannes D|JD|', 'Chen|Chen|C|0000-0003-2104-534X']
D000818:Animals D001823:Body Composition D003981:Diazoxide D059305:Diet, High-Fat D004734:Energy Metabolism D013006:Growth Hormone D006946:Hyperinsulinism D007328:Insulin D007333:Insulin Resistance D000078790:Insulin Secretion D050356:Lipid Metabolism D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008820:Mice, Obese D009765:Obesity
hyperinsulinemia growth hormone obesity energy metabolism diazoxide