Details

Autor(en) / Beteiligte

• Gupta, Deepali
• Burstein, Avi
• Shankar, Kripa
• Varshney, Salil
• Singh, Omprakash
• Paul, Subhojit
• Ogden, Sean
• Osborne-Lawrence, Sherri
• Metzger, Nathan
• Richard, Corine
• Zigman, Jeffrey

Titel

Ghrelin Deficiency Enhances Compensatory Increase of Beta-Cell Mass in Response to Obesity

Ist Teil von

• Obesity (Silver Spring, Md.), 2022-11, Vol.30, p.211-211

Ort / Verlag

Silver Spring: Blackwell Publishing Ltd

Erscheinungsjahr

2022

Quelle

Wiley Online Library Journals

Beschreibungen/Notizen

• Background: In obesity, pancreatic islets compensate for insulin resistance by increasing beta-cell mass and insulin release. The factors that regulate these beta-cell adaptations are incompletely described, yet likely include hormones. The stomach-derived hormone ghrelin represents one such potential regulatory factor. Not only does ghrelin increase blood glucose, inhibit insulin secretion, and impact the release of other islet hormones via both direct and indirect engagement of all traditional endocrine islet cell-types, but also new preliminary studies have revealed that ghrelin-knockout (KO) mice have larger islets. Notably, plasma ghrelin levels fall in the setting of obesity. Here, we investigated whether falls in ghrelin contribute to the obesity-related increase in beta-cell mass. Methods: Four to six-week-old male ghrelin-KO mice and wildtype (WT) littermates were fed standard chow or 60% high-fat diet (HFD) for 10 weeks, after which the anatomy of their islets was assessed, including insulin-immunoreactive (IR) area to measure beta-cell mass. Results: In both WT and ghrelin-KO mice, HFD increased insulin-IR area as compared to standard chow (by 60% and 78%, respectively). In standard chow-fed mice, insulin-IR area was 45% higher as a result of ghrelin deletion alone and was negatively correlated with plasma ghrelin (r=-0.07; p=0.04). In HFD-fed mice, insulin-IR area was 62% higher as a result of ghrelin deletion. Finally, insulin-IR area was 159% higher in HFD-fed ghrelin-KO mice than in standard chow-fed WT mice. Conclusions: In mouse islets, there is an effect of both obesity and ghrelin deletion on insulin-IR area and an interaction between the two. Specifically, the obesity-associated increase in insulin-IR area is exaggerated by ghrelin deletion. Since obesity is also associated with lower plasma ghrelin, we propose that the reduction in ghrelin that occurs in obesity helps facilitate the compensatory increase of beta-cell mass in response to obesity.