Growth Hormone Secretory Dynamics in Streptozotocin Diabetes: Evidence of a Role for Endogenous Circulating Somatostatin*

Publisher Website
Google Scholar
Abstract
The present studies examined the effects of streptozotocin-induced diabetes on the dynamics of GH, insulin (IRI), and glucose secretion in 68 chronically cannulated male rats. Animals were rendered diabetic by a single iv injection of streptozotocin (65 mg/kg) and sampled every 15 min for periods of 6h both before and at various times after treatment. The typical ultradian rhythm of GH secretion was evident in normal rats, with most peak GH values greater than 500 ng/ml (mean 6-h GH level, 125.3 ± 17.2 ng/ml). After streptozotocin administration, a significant depression in the amplitude of GH pulses was observed as early as 18 h post treatment (mean 6-h GH level, 54.4 ± 9.4 ng/ml; P < 0.01) concomitant with a marked elevation in plasma glucose levels and severe depression of plasma IRI levels. The amplitude and duration of the GH secretory episodes continued to decline over a 4-week period in the presence of persisting hyperglycemia and mostly undetectable plasma IRI levels. The pituitary GH concentration was not significantly altered 8 days post treatment. To elucidate the mechanism mediating the streptozotocininduced GH suppression response, the role of somatostatin (SRIF) was assessed by passive immunization with a specific SRIF antiserum. Two groups of streptozotocin-diabetic rats were administered iv 1 ml of either SRIF antiserum or normal sheep serum. The GH profiles of diabetic rats administered normal sheep serum continued to show a marked suppression of GH pulses (mean 6-h GH level, 69.5 ±7.8 ng/ml). In striking contrast, the GH profiles of diabetic SRIF antiserum-treated rats revealed a rapid (within 15–30 min) restoration of high amplitude GH pulses (500–800 ng/ml) and a significant elevation of GH trough levels. The mean 6-h GH level in these animals (150.3 ± 16.8 ng/ml) was significantly greater than that in normal sheep serumtreated controls (P < 0.01). In contrast to the effects on GH, no significant differences were observed in plasma glucose and IRI levels of diabetic SRIF antiserum-treated rats compared to diabetic normal sheep serum-treated controls. These results clearly demonstrate that the GH secretory episodes are markedly suppressed in the presence of streptozotocin-induced diabetes. Furthermore, the findings indicate that circulating SRIF plays a role in the GH suppression response observed in streptozotocin diabetes but is not involved in mediating the streptozotocin-induced effects on glucose and IRI.