Spontaneous recovery from non-insulin-dependent diabetes mellitus induced by neonatal streptozotocin treatment in spontaneously hypertensive rats

Abstract

We studied the long-term change in glycemic level in a model of non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR). Two-day-old male SHR were intraperitoneally injected with 37.5 to 75.0 mg/kg of STZ or vehicle alone as control. According to nonfasting plasma glucose levels at 12 weeks of age, rats were divided into mild (< 16.8 mmol/L) and severe (≥ 16.8 mmol/L) diabetes groups. In the mild diabetes group (n = 5), plasma glucose decreased significantly from 14.2 ± 1.8 mmol/L (mean ± SEM) at 20 weeks to 7.3 ± 0.3 mmol/L at 52 weeks ( P < .05) with progressing age. At 52 weeks, overnight fasting plasma glucose levels were significantly lower and serum immunoreactive insulin (IRI) was higher than in controls, respectively (4.1 ± 0.3 v 5.7 ± 0.3 mmol/L, P < 0.01; 625 ± 50 v 409 ± 50 pmol/L, P < .05), and insulinoma was found in 60% of rats. Therefore, the recovery from hyperglycemia may be attributed to the development of insulinoma. In the severe diabetes group (n = 6), plasma glucose remained high until 28 weeks (27.2 ± 1.5 mmol/L), but thereafter decreased with age, as it did in the mild diabetes group (13.7 ± 3.5 mmol/L at 52 weeks, P < .005). However, no insulinoma was found, and the mechanism for the recovery was unclear. The present study demonstrates that hyperglycemia spontaneously ameliorates in a neonatal STZ diabetes model of SHR, although this phenomenon may be strain-related.