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Impact of Sur1 gene inactivation on the morphology of mouse pancreatic endocrine tissue

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Abstract

In congenital hyperinsulinism of infancy (CHI), the loss of K-ATP channels (composed of Kir6.2 and SUR1 subunits) in β cells induces permanent insulin secretion and severe hypoglycaemia. By contrast, Sur1 −/− mice do not present such defects. We have investigated the impact of Sur1 gene inactivation on mouse islet cell morphology, structure and basic physiology. Pancreata were collected from young, adult and old wild-type (WT) and Sur1 −/− mice. After immunostaining for hormone, the total endocrine tissue, cell proportion, cell size and intra-insular distribution, hormone content and Glut-2 expression were quantified by morphometry. Basic physiological parameters were also measured. In young Sur1 −/− mice, the total endocrine tissue and proportion of β cells were higher (P<0.05) than in WT mice, whereas the proportion of δ cells was lower (P<0.01). In old Sur1 −/− mice, α cells were frequently located in the central regions of islets (unlike WT islets) and their proportion was increased (P<0.05). Glut-2 protein and mRNA levels were lower in old Sur1 −/− islets (P<0.02). Insulinaemia, fasting insulin and glucagon contents were equivalent in both groups of pancreata. Thus, the islets of Sur1 −/− mice present morphological modifications that have not been described in CHI and that might reflect an adaptive mechanism controlling insulin secretion in these mice.

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Acknowledgments

We thank M. Stevens and M. Nenquin for expert technical assistance and Dr. C. de Burbure for revising the manuscript.

Author information

Correspondence to Yves Guiot.

Additional information

This work was supported by grants 3.4616.05 (J.R.) and 9.4559.04 (C.S.) from the Fonds National de la Recherche Scientifique, Brussels, and by grant ARC 05/10–328 (I.M. and C.S.) from the Direction de la Recherche Scientifique de la Communauté Française de Belgique.

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Marhfour, I., Moulin, P., Marchandise, J. et al. Impact of Sur1 gene inactivation on the morphology of mouse pancreatic endocrine tissue. Cell Tissue Res 335, 505–515 (2009). https://doi.org/10.1007/s00441-008-0733-2

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Keywords

  • Congenital hyperinsulinism
  • Endocrine pancreatic cells
  • K-ATP channel
  • Morphology
  • Sur1 knockout mice