|Chacko, Shaji -|
|Haymond, Morey -|
|Sun, Yuxiang -|
|Marini, Juan -|
|Sauer, Pieter -|
|Ma, Xiaojun -|
|Sunehag, Agneta -|
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 8, 2012
Publication Date: May 1, 2012
Citation: Chacko, S.K., Haymond, M.W., Sun, Y., Marini, J.C., Sauer, P.J., Ma, X., Sunehag, A.L. 2012. Effect of ghrelin on glucose regulation in mice. American Journal of Physiology - Endocrinology and Metabolism. 302(9):E1055-E1062. Interpretive Summary: The objective of this research was to determine whether the hormone ghrelin secreted predominantly from the stomach has an effect on maintaining blood sugar concentration within the normal range. This study demonstrated that the hormone ghrelin is associated with the improvement of glucose control in the body via the regulation of glucose production during the immediate periods after the absorption of a meal. The findings from this research indicate that the effect of reduced ghrelin concentration on glucose regulation could be a potential explanation for the improvement of glucose control observed in patients after bariatric surgery.
Technical Abstract: Improvement of glucose metabolism after bariatric surgery appears to be from the composite effect of the alterations in multiple circulating gut hormone concentrations. However, their individual effect on glucose metabolism during different conditions is not clear. The objective of this study was to determine whether ghrelin has an impact on glycogenolysis, gluconeogenesis, and insulin sensitivity (using a mice model). Rate of appearance of glucose, glycogenolysis, and gluconeogenesis were measured in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and growth hormone secretagogue receptor knockout (Ghsr(-/-)) mice in the postabsorptive state. The physiological nature of the fasting condition was ascertained by a short-term fast commenced immediately at the end of the dark cycle. Concentrations of glucose and insulin were measured, and insulin resistance and hepatic insulin sensitivity were calculated. Glucose concentrations were not different among the groups during the food-deprived period. However, plasma insulin concentrations were lower in the ghrelin(-/-) and Ghsr(-/-) than WT mice. The rates of gluconeogenesis, glycogenolysis, and indexes of insulin sensitivity were higher in the ghrelin(-/-) and Ghsr(-/-) than WT mice during the postabsorptive state. Insulin receptor substrate 1 and glucose transporter 2 gene expressions in hepatic tissues of the ghrelin(-/-) and Ghsr(-/-) were higher compared with that in WT mice. This study demonstrates that gluconeogenesis and glycogenolysis are increased and insulin sensitivity is improved by the ablation of the ghrelin or growth hormone secretagogue receptor in mice.