Long-term prophylactic insulin treatment can prevent spontaneous diabetes and thyroiditis development in the diabetes-prone bio-breeding rat, while short-term treatment is ineffective

Abstract

Objective: Prophylactic insulin treatment has been demonstrated to reduce diabetes development in the diabetes-prone bio-breeding (DP-BB) rat. These prophylactic insulin treatments were given from 50 to 150 days of age. However, several data indicate that the diabetogenic process in DP-BB rats starts well before day 50. Design and methods: DP-BB rats were given bovine insulin pellets from 21 to 60 days of age, from 21 to 100 days of age and from 60 to 100 days of age. At 160 days of age a glucose tolerance test was performed to establish b-cell function and pancreata collected for histological analysis. Results: Prophylactic insulin treatment from 21 to 100 days of age gave a 42% reduction of diabetes incidence. The other treatment protocols had no effect. Non-diabetic rats treated with insulin from day 21 to 100 showed normal glucose tolerance and no sign of insulitis at 160 days of age. Non-diabetic rats of the control group and the other treatment groups showed normal glucose tolerance, but a slight increase of insulitis. Interestingly, the 21-100 day treated rats showed reduced serum levels of anti-colloid antibodies as compared with the control group. Conclusions: These results show that short-term prophylactic insulin treatment cannot prevent diabetes and thyroiditis development in DP-BB rats. The prophylactic treatment must start well before 60 days of age and be prolonged into the phase when the rats normally become diabetic to reduce diabetes incidence. These findings imply that in the human situation prophylactic insulin treatment must be prolonged over the normal range of diabetes onset.

Effects of beta-cell rest on beta-cell function: a review of clinical and preclinical data

“…The negative results of the DPT‐1, which countered the positive results seen in multiple animal trials, might be because of the low dose of insulin used to avoid hypoglycemia. Alternatively, animal data exist to suggest that β‐cell rest with insulin must be initiated at an earlier stage in the development of diabetes in order to prevent new‐onset disease (50). The Type 1 Diabetes TrialNet study group has initiated a follow‐up trial to further explore the potential role of oral insulin to delay or prevent type 1 diabetes (51).…”

SREBP-1c expression in Schwann cells is affected by diabetes and nutritional status

“…Diabetic animals were treated with bovine insulin pellets (implanted s.c., release 1.5 -2 IU/24 hr; Linplant Scarborough, Ontario, Canada) as described (Visser et al, 2003). Insulin pellets were removed from rats between 3-16 days of diabetes and subsequently, both diabetic and age-matched non-diabetic controls were either fasted for 24h and sacrificed (fasted group), or fasted for 18h and allowed to refeed for a subsequent 6h and then sacrificed (fasted -refed group).…”

Potential mechanisms explaining why hydrolyzed casein‐based diets outclass single amino acid‐based diets in the prevention of autoimmune diabetes in diabetes‐prone BB rats

“…These infiltrating immune cells destroy the insulin producing ß ‐cells. The degree of insulitis was rated on a scale of 1–4 as described previously by Visser et al . Briefly, 1, normal islet appearance and no infiltration; 2, mild insulitis, where macrophages/mononuclear cells are around and not affecting more than 50% of the islet; 3, severe insulitis, where macrophages/mononuclear cells completely penetrate and infiltrate the islets; 4, end‐stage islets.…”