Dynamic Time-Course Studies of the Spontaneously Diabetic BB Wistar Rat, I. Longitudinal Profiles of Plasma Growth Hormone, Insulin, and Glucose*

Abstract

The time course of changes in plasma levels of GH, insulin (IRI), and glucose were examined in the spontaneously diabetic BB Wistar rat. Sequential 6-h GH, IRI, and glucose secretory profiles were obtained at various times before (1–42 days) and after (1–49 days) the onset of diabetes (glycosuria). Age-matched nondiabetic littermates served as controls. In the prediabetic (pre-glycosuric) stage, the typical pulsatile pattern of GH secretion was evident in all rats. No disruption in either the amplitude or the period of the GH rhythm was observed as close as 1 day before the detection of glycosuria. There was also no significant difference in basal plasma IRI and glucose levels compared to those in nondiabetic littermates. Furthermore, no significant difference was observed in either the glucose or IRI response to an iv glucose challenge 10 days before onset, although the IRI response to oral feeding was blunted 1–3 days before overt glycosuria. After the onset of diabetes, marked hyperglycemia and hypoinsulinemia were observed in all animals for the duration of the study. In stable diabetic rats which were gaining weight and nonketotic, there was no significant effect on the GH rhythm in the early phase of the disease (1–5 days post onset). In unstable diabetics which were losing weight and ketosis prone, a significant depression in the amplitude of GH secretory bursts was observed as early as 1 day post detection. As the disease progressed in both groups of diabetics, the amplitude and duration of the GH secretory episodes declined markedly, and normal GH periodicity was not evident. The pituitary GH concentration was significantly reduced in both unstable (7–22 days post detection) and stable (41–63 days post detection) diabetic rats compared to that in nondiabetic littermates. Taken together, these findings in the BB rat indicate that the prediabetic phase is characterized by normal GH secretory dynamics and normal glucose and IRI levels until a few days before overt disease. As the disease progresses and changes in body weight occur, the GH secretory episodes are markedly suppressed, probably via decreased synthesis by the pituitary gland.