Neonatal treatment with beta-cell stimulatory agents reduces the incidence of diabetes in BB rats.

Karsten Buschard,Kim Aaen,Charlotte R Pedersen,Michael Wøllike Hansen,Ida Hageman,Merete Jørgensen,Knud Josefsen,Susanne V Hansen,Troels W Kjaer,Troels Bock

doi:10.1155/edr.2000.1

Karsten Buschard, Kim Aaen + Show 8 more

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https://doi.org/10.1155/edr.2000.1

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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.

Highlights

The idea of neonatal stimulation of beta cells in BB rats and NOD mice in order to reduce the diabetes incidence (Buschard et al, 1990) is inspired by two observations
The present investigations have shown in largescale experiments that the diabetes incidence in BB rats can be reduced by neonatal injections of various agents known to stimulate insulin secretion by different mechanisms
In a barrier-confined colony of BB rats with a high diabetes incidence, this was moderately but significantly reduced and the onset of diabetes delayed after neonatal treatment with arginine and glucose combined, but given only once a day (Hansen et al, 1993)

Summary

Introduction

The idea of neonatal stimulation of beta cells in BB rats and NOD mice in order to reduce the diabetes incidence (Buschard et al, 1990) is inspired by two observations. Type 1 diabetes is less frequent in children of Type 1 diabetic mothers than in children of diabetic fathers (Warram et al, 1984; Tilli and K6bberling, 1987; Rjasanowski et al., 1990); in other words: a Type 1 diabetic pregnancy seems to partially protect against development of Type I diabetes in the offspring. A growing knowledge indicates that if the mothers develop Type 1 diabetes after the pregnancy, the children seem to have the same diabetes risk as children of diabetic fathers (Warram et al, 1984; Lorentzen et al, 1998). This has been found for the antigens corresponding to the (monoclonal) antibodies IC2 (Buschard et al, 1988; Aaen et al, 1990), A2B5 (Aaen et al, 1990; Eisenbarth et al, 1982), R2D6 (Appel et al, 1989), and ICA (McCulloch et al, 1991), and for GAD (Hao et al, 1994) and 64kDa antigen (K/impe et al, 1989)

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