Paracrine signaling by pancreatic delta cells determines the glycemic set point in mice

Huang, J. L.; Lee, S.; Pourhosseinzadeh, M. S.; Krämer, N.; Guillen, J. V.; Cinque, N. H.; Aniceto, P. A.; Koike, S.; Huising, M. O.

doi:10.1101/2022.06.29.496132

bioRxiv · 10.1101/2022.06.29.496132

Paracrine signaling by pancreatic delta cells determines the glycemic set point in mice

Huang, J. L.·Lee, S.·Pourhosseinzadeh, M. S.·Krämer, N.·Guillen, J. V.·Cinque, N. H.·Aniceto, P. A.·Koike, S.·Huising, M. O.

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Abstract

Pancreatic islets contain several endocrine cell types that coordinate to maintain blood glucose homeostasis. While {beta} and cells are thought to be the main drivers of glucose homeostasis through insulin and glucagon secretion respectively, the contribution of {delta} cells and somatostatin (SST) secretion to establishing the glycemic set point remains unresolved. Here we remove local SST signaling from {delta} cells within the pancreatic islet to investigate their contribution to the glycemic set point. Our data demonstrate that ablating {delta} cells or SST leads to a sustained decrease in the glycemic set point. This coincides with a decreased glucose threshold for insulin response from {beta} cells, leading to increased insulin secretion to the same glucose challenge. In contrast, cell ablation had no effect on glycemic set point. Collectively, these data establish the physiological role of {delta} cells in determining the glycemic set point through their interaction with {beta} cells.

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Huang, J. L., Lee, S., Pourhosseinzadeh, M. S., Krämer, N., Guillen, J. V., Cinque, N. H., Aniceto, P. A., Koike, S., Huising, M. O.. 2022-07-02. Paracrine signaling by pancreatic delta cells determines the glycemic set point in mice. https://doi.org/10.1101/2022.06.29.496132

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