Abstract
The purpose of this study was to investigate the effect of a treatment by gamma-hydroxybutyrate
(GHB) and nicotinamide (NA) on low-dose streptozotocin (STZ)-induced diabetes in mice.
Mean plasma glucose level was significantly elevated in mice given STZ by day 12 after
the first STZ injection compared to controls (15.0 ± 4.7 vs 8.0 ± 1.6 mmol/l, p <
0.001) and 100% of the animals were severely diabetic by day 18. Plasma glucose levels
remained in the normal range and no diabetic values were found in mice treated with
combined treatment by GHB and NA for 25 days. However, hyperglycemia and glycosuria
appeared within one week after discontinuation of the treatment. Treatment by either
GHB or NA alone had only a slight and transient effect in preventing hyperglycemia.
In vitro experiments on isolated pancreatic islets demonstrated that STZ-induced loss
of insulin response to glucose was also counteracted by incubation with GHB and NA
(Peak insulin response to 16.4 mM glucose: 0.69 ± 0.31 vs 3.03 ± 0.67 µU/islet/min),
but not by GHB or NA alone. These results indicate that GHB and NA have complementary
effects in preventing STZ-induced beta cell damage both in vivo and in vitro. This
should be taken into account for future preventive strategies in human insulin-dependent
diabetes mellitus.
Key words
Streptozotocin - Diabetes Mellitus - Nicotinamide - Gamma-Hydroxybutyrate
