Hemorrhage results in hepatic insulin-sensitizing substance-dependent insulin resistance mediated by somatostatin in rats.

Abstract

BACKGROUND/AIMS:

Acute hemorrhage results in hyperglycemia regulated in a redundant manner by adrenal catecholamines and hepatic sympathetic nerves. In addition, insulin secretion is suppressed and insulin resistance is accounted for completely by elimination of the hepatic insulin-sensitizing substance (HISS) component of insulin action. Blockade of HISS action secondary to blood loss leads to a state known as HISS-dependent insulin resistance (HDIR) which results in a decrease in the glucose disposal action of insulin by 33 +/- 3%.

METHODS:

This paper describes nine studies that have explored the neuroendocrine control of HDIR that is produced in response to the stress of blood loss. The rapid insulin sensitivity test (RIST), a transient euglycemic clamp, was used to measure insulin sensitivity. To test the role of the adrenergic system, alpha- and beta-adrenergic receptor antagonists, phentolamine and propranolol, were tested for the ability to block HDIR produced by hemorrhage.

RESULTS:

Neither intervention was effective (32 +/- 6 and 36 +/- 3%, respectively). Exogenous somatostatin was shown to produce HDIR that could be blocked by the somatostatin receptor antagonist, cyclosomatostatin. Cyclosomatostatin completely blocked the development of HDIR that occurred following hemorrhage (RIST index 214 +/- 9 control, 218 +/- 9 mg glucose/kg body weight after cyclosomatostatin plus hemorrhage).

CONCLUSIONS:

The adrenergic system is not involved in producing HDIR in response to hemorrhage. Somatostatin appears to be the hormonal regulator of this response and it is suggested that the somatostatin derives from a neural origin within the liver.

• Authors: Larissa I Seredycz, W Wayne Lautt
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 84 Issue 2 Pg. 94-102 ( 2006) ISSN: 0028-3835 [Print] Switzerland
• PMID: 17202832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic Agents
• Blood Glucose
• Hormones
• Somatostatin
• Propranolol
• Phentolamine

Topics

• Adrenergic Agents (pharmacology)
• Analysis of Variance
• Animals
• Blood Glucose (metabolism)
• Glucose Clamp Technique
• Hemorrhage (metabolism)
• Hormones (physiology)
• Insulin Resistance (physiology)
• Liver (drug effects, metabolism)
• Male
• Phentolamine (pharmacology)
• Propranolol (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Somatostatin (physiology)
• Statistics, Nonparametric