1. Paracrine signalling by pancreatic δ cells determines the glycaemic set point in mice
- Author
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Huang, Jessica L, Pourhosseinzadeh, Mohammad S, Lee, Sharon, Krämer, Niels, Guillen, Jaresley V, Cinque, Naomi H, Aniceto, Paola, Momen, Ariana T, Koike, Shinichiro, and Huising, Mark O
- Subjects
Medical Biochemistry and Metabolomics ,Medical Physiology ,Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Diabetes ,Digestive Diseases ,Metabolic and endocrine ,Animals ,Mice ,Somatostatin-Secreting Cells ,Islets of Langerhans ,Glucagon ,Insulin ,Glucose ,Medical biochemistry and metabolomics ,Medical physiology ,Nutrition and dietetics - Abstract
While pancreatic β and α cells are considered the main drivers of blood glucose homeostasis through insulin and glucagon secretion, the contribution of δ cells and somatostatin (SST) secretion to glucose homeostasis remains unresolved. Here we provide a quantitative assessment of the physiological contribution of δ cells to the glycaemic set point in mice. Employing three orthogonal mouse models to remove SST signalling within the pancreas or transplanted islets, we demonstrate that ablating δ cells or SST leads to a sustained decrease in the glycaemic set point. This reduction coincides with a decreased glucose threshold for insulin response from β cells, leading to increased insulin secretion to the same glucose challenge. Our data demonstrate that β cells are sufficient to maintain stable glycaemia and reveal that the physiological role of δ cells is to provide tonic feedback inhibition that reduces the β cell glucose threshold and consequently lowers the glycaemic set point in vivo.
- Published
- 2024