Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2013 Apr 22;8(4):e61822. doi: 10.1371/journal.pone.0061822. Print 2013.
Type 2 Diabetes is a global health burden and based on current estimates will become an even larger problem in the future. Developing new strategies to prevent and treat diabetes is a scientific challenge of high priority. The stomach hormone ghrelin has been associated with playing a role in the regulation of glucose homeostasis. However, its precise mechanism and impact on whole glucose metabolism remains to be elucidated. This study aims to clarify the role of the two ghrelin isoforms acyl- and desacyl ghrelin in regulating glucose homeostasis. Therefore ghrelin activating enzyme Ghrelin-O-acyltransferase (GOAT) was ablated in leptin-deficient ob/ob mice to study whether specific acyl ghrelin deficiency or desacyl ghrelin abundance modifies glucose tolerance on a massively obese background. As targeted deletion of acyl ghrelin does not improve glucose homeostasis in our GOAT-ob/ob mouse model we conclude that neither acyl ghrelin nor the increased ratio of desacyl/acyl ghrelin is crucial for controlling glucose homeostasis in the here presented model of massive obesity induced by leptin deficiency.
2 型糖尿病是全球健康负担，根据目前的估计，未来它将成为一个更大的问题。开发预防和治疗糖尿病的新策略是一个高度优先的科学挑战。胃激素 ghrelin 一直与调节葡萄糖稳态有关。然而，其确切的机制及其对整个葡萄糖代谢的影响仍有待阐明。本研究旨在阐明两种 ghrelin 同种型酰基和脱酰基 ghrelin 在调节葡萄糖稳态中的作用。因此，在瘦素缺乏型 ob/ob 小鼠中敲除了 ghrelin 激活酶 Ghrelin-O-acyltransferase (GOAT)，以研究特定的酰基 ghrelin 缺乏或脱酰基 ghrelin 丰度是否会在肥胖背景下改变葡萄糖耐量。由于在我们的 GOAT-ob/ob 小鼠模型中，酰基 ghrelin 的靶向缺失并不能改善葡萄糖稳态，我们得出结论，在由瘦素缺乏引起的肥胖模型中，酰基 ghrelin 或脱酰基/酰基 ghrelin 的比值增加都不是控制葡萄糖稳态的关键。
