Impact of Sur1 gene inactivation on the morphology of mouse pancreatic endocrine tissue.
In congenital hyperinsulinism of infancy (CHI), the loss of K-ATP channels (composed of Kir6.2 and SUR1 subunits) in beta 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 beta cells were higher (P<0.05) than in WT mice, whereas the proportion of delta cells was lower (P<0.01). In old Sur1 ( -/- ) mice, alpha 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.
Marhfour
Ihsane
I
Department of Pathology, Faculty of Medicine, Université Catholique de Louvain, Brussels, Belgium.
Moulin
Pierre
P
Marchandise
Joëlle
J
Rahier
Jacques
J
Sempoux
Christine
C
Guiot
Yves
Y
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics*; D011955:Receptors, Drug / Q000172:deficiency / Q000235:genetics*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D001786:Blood Glucose; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D005934:Glucagon