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

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 (less than 16.8 mmol/L) and severe (greater than or equal to 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 less than .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 less than 0.01; 625 +/- 50 v 409 +/- 50 pmol/L, P less than .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 less than .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.