Neonatal Treatment With Beta‐Cell Stimulatory Agents Reduces the Incidence of Diabetes in BB Rats

Abstract

The aim of the study was to investigate whether various beta-cell stimulatory drugs, given neonatally, influence the incidence of diabetes in BB rats. Newborn BB rats were treated twice daily for 6 days and diabetes development was observed during the following 200-day study period. Compared to a diabetes incidence of 63.8% in 163 control BB rats which received saline or were untreated, the percentage of experimental BB rats that developed diabetes was as follows in the different subgroups: arginineglucose: 47% (n= 73, p < 0.02); glucagon: 37% (n = 93, p < 0.0001); tolbutamide-glucose: 36% (n = 58, p < 0.0005); and theophylline-glucose: 39% (n = 41, p < 0.005). A long-term arginine-glucose treatment was not superior to the shorter neonatal treatment. Histological examination revealed a higher degree of insulitis in diabetic than in non-diabetic animals but no difference according to the kind of treatment was observed. Finally, we found that the diabetes incidence in BB rats was higher in the first litter compared to subsequent litters (p = 0.04). Thus, neonatal treatment with various beta-cell stimulatory agents reduces diabetes incidence in BB rats. The theory behind the study, that the treatment accelerates beta-cell maturation leading to increased immunological tolerance towards beta cells, is discussed.

What causes type 1 diabetes? Lessons from animal models

“…arginine (68, 69). In both cases the beta cells are phenotypic adult instead of being the usual fetal type, and the risk of later development of T1D is reduced (68–70). This emphasizes the need for a good antigenic self response in a given tissue at the neonatal stage in order to avoid later breakdown of tolerance.…”

“…An adult phenotype of beta cells is not achieved before weeks after birth, unless the baby is born to a diabetic mother or – in animal models – unless the beta cells have been stimulated to secrete insulin by e.g. arginine ( 68 , 69 ). In both cases the beta cells are phenotypic adult instead of being the usual fetal type, and the risk of later development of T1D is reduced ( 68 – 70 ).…”

Type-specific human papillomavirus detection in cervical smears in Romania

“…An adult phenotype of beta cells is not achieved before weeks after birth, unless the baby is born to a diabetic mother or – in animal models – unless the beta cells have been stimulated to secrete insulin by e.g. arginine (68, 69). In both cases the beta cells are phenotypic adult instead of being the usual fetal type, and the risk of later development of T1D is reduced (68–70).…”

Effects of a vitamin D3 analog on diabetes in the bio breeding (BB) rat

“…Moreover, there is substantial disagreement with regard to the effects of the administration of oral insulin with adjuvants [Matsumoto et al, 1986;Hartmann et al, 1997;Kolb et al, 1997;Bellmann et al, 1998;Buschard et al, 2000]. Therefore, we observed the effects of a vitamin D 3 analog and insulin treatment in the BB rat model.…”