Abstract
The somatostatin (SST)-secreting cells were mainly distributed in the pancreatic islets, brain, stomach and intestine in mammals and have many physiological functions. In particular, the SST-secreting δ cell is the third most common cell type in the islets of Langerhans. Recent studies have suggested that dysregulation of paracrine interaction between the pancreatic δ cells and β cells results in impaired glucose homeostasis and contributes to diabetes development. However, direct evidence of the functional importance of SST cells in glucose homeostasis control is still lacking. In the present study, we specifically ablated SST-secreting cells by crossing Sst-cre transgenic mice with R26DTA mice (SstCreR26DTA). The SstCreR26DTA mice exhibited neonatal death. The life spans of these mice with severe hypoglycemia were extended by glucose supplementation. Moreover, we observed that SST cells deficiency led to increased insulin content and excessive insulin release, which might contribute to the observed hypoglycemia. Unexpectedly, although SST is critical for the regulation of insulin content, factors other than SST that are produced by pancreatic δ cells via their endogenous corticotropin-releasing hormone receptor 2 (CRHR2) activity play the main roles in maintaining normal insulin release, as well as neonatal glucose homeostasis in the resting state. Taken together, our results identified that the SST cells in neonatal mouse played critical role in control of insulin release and normal islet function. Moreover, we provided direct in vivo evidence of the functional importance of the SST cells, which are essential for neonatal survival and the maintenance of glucose homeostasis.
Highlights
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction The maintenance of blood glucose homeostasis is critical for many physiological processes, which are tightly regulated by the concerted actions of hormones, such as glucocorticoids, epinephrine produced by the adrenal glands, and insulin and glucagon generated in pancreatic islets
Immunofluorescence and quantitative reverse-transcriptase PCR analyses confirmed that the expression of SST in the pancreatic islets, stomach and brain of the SstCre R26DTA mice was abrogated compared with the expression in their Sst-cre littermates (Figs. 1a, b, Figure S2A-C)
The SstCre R26DTA mice appeared normal at birth, they displayed significantly reduced blood glucose levels and body weights compared with Sst-cre mice (Figs. 1c, d)
Summary
The maintenance of blood glucose homeostasis is critical for many physiological processes, which are tightly regulated by the concerted actions of hormones, such as glucocorticoids, epinephrine produced by the adrenal glands, and insulin and glucagon generated in pancreatic islets. Li et al Cell Death and Disease (2018)9:682 and hyperglycemia-induced early death[5] Mice lacking both the Arx and the Pax[4] genes display significant shrinkage of both α- and β-cell lineages and die neonatally because of lethal hyperglycemia[6]. Whereas somatostatin gene knockout mice display increased glucagon and insulin release in response to nutrient stimuli compared with control mice, they show similar growth curves, islet sizes, hormone contents, resting normoglycemia and insulin sensitivity[7,11]. These observations imply that SSTproducing cells may be dispensable for resting blood glucose control
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.