Gut-derived proteolysis during insulin-induced hypoglycemia: the pain that breaks down the gut.
The metabolic events associated with early response to injury have received little attention because of the confounding effects of the hemodynamic alterations that normally occur during this early phase. We have used a well established and reproducible model of insulin-induced hypoglycemia in the conscious dog to define the glucose and amino acid kinetic alterations as well as the hormonal and interorgan amino acid and gluconeogenic precursor flux characteristics of the "ebb" phase of postinjury metabolism. The results from our whole-body response have demonstrated on enhanced rate of whole body proteolysis and amino acid oxidation. The site of the majority of the proteolytic response has been demonstrated to be the extra-hepatic splanchnic tissues or gut. These findings have been supported by studies focusing on the specific organ changes, which have demonstrated alterations compatible with impaired proliferation at the level of the gut mucosa. Furthermore, the regulation of this gut-derived proteolysis has been demonstrated to be mediated by the glucopenia at the level of the central nervous system. The specific site of this response is still elusive; however, the mediators seem to involve not only the traditional hormonal and neurotransmitter pathways but also the release of endogenous opioids and opiates. Although a cause-effect relationship has not yet been demonstrated for the control of gut-derived proteolysis by opioids and opiates, we present evidence that leads us to hypothesize that relationship as a possible regulatory mechanism.
Molina
P E
PE
Department of Surgery, State University of New York at Stony Brook 11794-8191, USA.
Abumrad
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NN
D000818:Animals; D001921:Brain / Q000503:physiopathology; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin; D007413:Intestinal Mucosa / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism
D007328:Insulin; D011506:Proteins