Low-protein diet during early life causes a reduction in the frequency of cells immunopositive for nestin and CD34 in both pancreatic ducts and islets in the rat.
Feeding a low-protein (LP) diet to pregnant and lactating rats impairs pancreatic islet mass and insulin release in the offspring, leading to glucose intolerance as adults. We hypothesized that an LP diet changes the number of pancreatic endocrine precursor cells or cells supporting endocrine cell neogenesis. Pregnant rats were given LP (8% protein) or a control (20% protein) diet from conception until postnatal d 21. Cells containing nestin, CD34, or c-Kit were quantified in pancreata of the offspring. Stellate cells immunoreactive for nestin were seen to be adjacent to ductal epithelium and were resident within the islets. These were proliferative and immunonegative for cytokeratin 20, fibronectin, tyrosine hydroxylase, pancreatic duodenal homeobox 1, Nk homeodomain transcription factor 6.1, or insulin, but expressed vimentin. Approximately 20% of islet nestin-positive cells also expressed the endothelial cell marker platelet endothelial cell adhesion molecule-1. Both ducts and islets also contained CD34- and c-Kit-positive cells with similar morphology to those expressing nestin. Offspring from rats fed the LP diet had significantly less nestin/CD34-positive cells and reduced expression of nestin mRNA. Within islets, there was an associated decrease in cell proliferation and in cells immunopositive for pancreatic duodenal homeobox 1. Nestin-positive cell number within islets correlated positively with the percent area of beta-cells. Supplementation of pregnant and lactating rats with taurine reversed the deficits in mean islet area and nestin-positive cells caused by the LP diet within the islets of the offspring. Nutritional programming of postnatal beta-cell mass may involve an altered abundance of cells expressing nestin and/or CD34, which may limit endocrine cell development.
Joanette
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EA
Lawson Health Research Institute, St. Joseph's Health Care, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2.
Reusens
B
B
Arany
E
E
Thyssen
S
S
Remacle
R C
RC
Hill
D J
DJ
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D004044:Dietary Proteins / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005333:Fetus / Q000378:metabolism; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D007774:Lactation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D010183:Pancreatic Ducts / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000008:administration & dosage
D018952:Antigens, CD34; D004044:Dietary Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D013654:Taurine