Intracerebroventricular administration of somatostatin octapeptide counteracts the hormonal and metabolic responses to stress in normal and diabetic dogs

Intracerebroventricular (ICV) injection of carbachol elicits hormonal and metabolic responses similar to moderate stress. In normal dogs, ICV carbachol stimulated marked counterregulatory hormone release, but altered plasma glucose only marginally because the marked increment in glucose production (R a) was almost matched by the increment of utilization (R d), even though plasma insulin was unchanged. In alloxan-diabetic dogs, R d did not match R a and plasma glucose increased substantially. Since somatostatin octapeptide (ODT8-SS) inhibits some sympathetic mechanisms of the stress response, we explored the extent to which ODT8-SS can alleviate the counterregulatory responses to stress induced by carbachol, and particularly whether it can restore glycemic control in diabetes. ODT8-SS (20 nmol) was ICV-injected (1) in normal dogs (n = 5), and (2) prior to ICV carbachol before (n = 7) and after (n = 6) the induction of alloxan-diabetes. ODT8-SS did not affect basal values, but when administered before ICV carbachol there were no significant increments in plasma epinephrine, cortisol, arginine vasopressin (AVP), insulin, glucose, or lactate. There were significant increases in norepinephrine, glucagon, R a, R d, and the glucose metabolic clearance rate (MCR), although they were much smaller than seen previously with ICV carbachol alone. After induction of alloxan-diabetes, R d and MCR did not change with ICV ODT8-SS and carbachol as in normal dogs, but norepinephrine, epinephrine, glucagon, lactate, plasma glucose, and R a increased, although with the exception of glucagon these increases were much smaller than seen previously with ICV carbachol alone. ODT8-SS administered before ICV carbachol in normal or diabetic animals resulted in increased free fatty acid (FFA) levels. The increases in glycerol were less than and those in FFA greater than seen previously with ICV carbachol alone. Since ODT8-SS does not alter basal counterregulatory hormone release but suppresses the release during stress, this is a useful probe to analyze some of the metabolic responses to stress. When the response to carbachol from our previous report is compared with the responses to carbachol + ODT8-SS, it is indicated that the stress-related increase in R a was consistent with stimulation of the sympathetic nervous system, whereas increased R d is related to an unknown stress-related neuroendocrine mechanism that requires a permissive effect of insulin, since it was not seen in the f