Preventive and Therapeutic Effects of Large-Dose Nicotinamide Injections on Diabetes Associated with Insulitis: An Observation in Nonobese Diabetic (NOD) Mice

Abstract

This experiment was undertaken to explore a novel method of therapy for insulin-dependent diabetes mellitus (IDDM), using nonobese diabetic (NOD) mice that had symptoms and histologic changes similar to those of human IDDM patients. We examined preventive and therapeutic effects of large-dose nicotinamide administration on diabetes in NOD mice. Eighteen young female NOD mice without glycosuria were randomly divided into two groups; nine received subcutaneous nicotinamide (0.5 mg/g body wt) injections every day and the other nine were maintained as a control group and not injected. After 40 days, all of the mice given nicotinamide showed almost normal glucose tolerance and only mild insulitis on histologic study. On the other hand, marked glycosuria and severe insulitis were observed in six of the nine mice not injected. Four of six NOD mice given nicotinamide from the day of the first occurrence of marked glycosuria displayed a disappearance of glycosuria and an improvement in glucose tolerance during the therapy; however, urine sugar became negative in only one of six mice that received nicotinamide from 1 to 2 wk after the onset of marked glycosuria. These results indicate that nicotinamide has preventive and therapeutic effects on diabetes in NOD mice, and suggest the reversibility of B-cell damage, at least at a very early stage of IDDM.

Interleukin 1 induces new protein formation in isolated rat islets of Langerhans

“…This would be potentially very harmful to beta-cell survival (10). In this context it is worth noticing that free radical scavengers, in¬ cluding SOD, given to animals prevent diabetes development (24) and graft destruction in the NOD mouse transplanted with culture condi¬ tioned islet allografts (25). Thus, further studies of IL-1 induced protein formation in islets in culture and in vivo may provide information important for our understanding of the pathogenesis of IDDM.…”

Early events in islets and pancreatic lymph nodes in autoimmune diabetes

“…PARP is a nuclear DNA repair enzyme that consumes NAD in response to DNA strand breaks. Its excessive activation seems particularly deleterious to pancreatic beta cells, and nicotinamide, an inhibitor of PARP-1, has shown beneficial effects in the prevention of NOD insulitis and diabetes [23]. However, NOD mice with a PARP disrupted gene developed both spontaneous and induced forms of diabetes, which suggest the existence of PARP-1-independent pathways of beta-cell death [24].…”

Effects of Micro-Encapsulation on Morphology and Endocrine Function of Cryopreserved Neonatal Porcine Islet-Like Cell Clusters

“…then micro-encapsulated. We thought that when encapsulated ICCs were cryopreserved, injured ICCs were exposed to some chemical mediators leaking from degenerated cells in the capsule (31). And the cryo-injury would reduce the strength and the immunoisolation effects of the micro-capsule.…”