Prevention of Autoimmune Diabetes by Oral Administration of Syngeneic Pancreatic Extract to Young NOD Mice

Abstract

Oral administration of relevant autoantigens is being considered as a realistic approach for the prevention of several autoimmune diseases. In this study we administered, orally, to young female NOD/Ak mice (diabetes incidence, 40%) and NOD/LtJ mice (diabetes incidence, 70%) whole pancreatic extract on days 19, 20, 21, 22, 23, 26, and 27 and studied its effects on the development of diabetes until day 250. The cumulative incidence of diabetes in both the colonies after pancreatic extract treatment was compared with the incidence after oral administration of syngeneic liver extract or in untreated mice. In the NOD/Ak mice, the incidence of diabetes in the pancreatic extract group was significantly lower (6%; n = 34, p = 0.004) and was delayed compared with 33% in the liver group (n = 34) and 44% in the untreated group (n = 18). Significant protection from diabetes and a delay in its onset also were observed in the NOD/LtJ mice treated with pancreatic extract (16%; n = 19, p = 0.002) compared with those liver extract treated (72%; n = 18) and in untreated mice (60%; n = 22). Pancreatic histology at day 90 from all the study groups showed that the protection from diabetes in the pancreatic-extract group was not associated with reduced insulitis. We speculate that the marked disease protection observed in this study with orally administered pancreatic extract may be associated with the presence of immunoregulatory cells with a predominant Th2 cytokine bias. Our studies may have implications for the prevention of insulin-dependent diabetes mellitus (IDDM) in humans.

Intradermal or Oral Delivery of GAD-Encoding Genetic Vaccines Suppresses Type 1 Diabetes

“…However, there was no correlation between decreased insulitis and decreased diabetes onset. This absence of correlation between islet inflammation and disease onset has been observed previously, and could be the result of infiltration of islets by different populations of leukocytes (Ramiya et al, 1997;Reddy et al, 2000).…”

Induction of pancreatic β cell gene expression in mesenchymal stem cells

“…Interestingly, signals from mesenchymal stem cells (MSCs) play a significant role in the development of normal pancreas. Reddy et al () showed that administration of whole pancreatic extract to non‐obese diabetic (NOD) mice inhibited autoimmune diabetes (Reddy et al, ). Subcutaneous administration of pancreas extract to human decreased blood glucose and increased utilization of carbohydrates (Banting et al, ).…”

Efficient and Simple Production of Insulin-Producing Cells from Embryonal Carcinoma Stem Cells Using Mouse Neonate Pancreas Extract, As a Natural Inducer

“…Experimental studies demonstrated that the supplementation of oral nutrition with pancreatic extract-enriched diet improved the nutritional status of the aged rats [13], [14]. Reddy et al showed that the oral administration of whole pancreas extract to young non-obese diabetic (NOD) mice, prevented autoimmune diabetes [15]. Rat pancreatic extract (RPE) enhanced the expression of the required transcription factors for pancreas development [16].…”