Effects of INGAP on islet neoformation in diabetes‐prone BioBreeding rats fed a protective hydrolyzed casein diet

Type 1 diabetes results from autoimmune destruction of pancreatic β-cells. β-cell neoformation has been shown to increase in response to islet neogenesis-associated protein (INGAP) in hamsters. Using immunohistochemistry and morphometry, INGAP effects in diabetes-prone BioBreeding (BBdp) rats were investigated. At 23 d, rats were fed a hydrolyzed casein (HC) diet or a cereal-based NTP-2000 diet. Rats were administered saline intraperitoneally (n=7) or 250 μg of INGAP-peptide (n=7) twice daily for two weeks and killed at 45 d. In HC-fed rats, the number of small and total islets was greater in INGAP-treated rats compared with controls (59 ± 17 vs. 37 ± 8 islets/cm2, mean ± SD, p=0.01 and 143 ± 19 vs. 114 ± 24 islets/cm2, p<0.03). In rats given INGAP, insulin+extra-islet clusters, markers of islet neoformation, were more frequent in those fed HC compared with NTP (82 ± 20 vs. 46 ± 8 clusters/cm2, p<0.01). HC-fed rats given INGAP had a higher percentage of BrdU+/insulin+ clusters compared with controls, indicating enhanced proliferation (26.0 ± 7.6 vs. 13.1 ± 2.7%, p<0.001). INGAP-treated rats fed either an HC or NTP diet had a higher percentage of insulin+ cells in small ducts compared with saline controls. These findings demonstrate the presence of INGAP-stimulated β-cell neoformation, some aspects of which were further enhanced in BBdp rats fed a protective HC diet. (Supported by CDA and CIHR; CP and GSW contributed equally).