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 (Ra) was almost matched by the increment of utilization (Rd), even though plasma
insulin was unchanged. In
alloxan-diabetic dogs, Rd did not match Ra 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, Ra, Rd, and the
glucose metabolic clearance rate (MCR), although they were much smaller than seen previously with ICV
carbachol alone. After induction of
alloxan-diabetes, Rd and MCR did not change with ICV
ODT8-SS and
carbachol as in normal dogs, but
norepinephrine,
epinephrine,
glucagon,
lactate, plasma
glucose, and Ra 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 Ra was consistent with stimulation of the sympathetic nervous system, whereas increased Rd is related to an unknown stress-related neuroendocrine mechanism that requires a permissive effect of
insulin, since it was not seen in the frankly diabetic animals. We hypothesize that the stress-induced increase in Rd occurs not only in muscle but also in adipocytes, and that the
somatostatin-induced attenuation of Rd decreased FFA re-esterification and consequently markedly increased stress-induced FFA release.(ABSTRACT TRUNCATED AT 400 WORDS)