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The Locus for Hypoglycemic Detection Shifts With the Rate of Fall in Glycemia

The Role of Portal–Superior Mesenteric Vein Glucose Sensing

¹ Department of Kinesiology, University of Southern California, Los Angeles, California
² Department of Biological Sciences, University of Southern California, Los Angeles, California

Corresponding author: Dr. Casey M. Donovan, University of Southern California, Departments of Kinesiology and Integrative Biology, 3560 Watt Way, PED 107, Los Angeles, CA 90089-0652. E-mail: donovan{at}usc.edu

Abbreviations: CGRP, calcitonin gene–related peptide; CNS, central nervous system

OBJECTIVE—To ascertain whether portal glucose sensing extends beyond the portal vein to the superior mesenteric vein and then test whether the role of portal–superior mesenteric glucose sensors varies with the rate of fall in glycemia.

RESEARCH DESIGN AND METHODS—Chronically cannulated rats underwent afferent ablation of the portal vein (PV) or portal and superior mesenteric veins (PMV) or sham operation (control). One week later, animals underwent hyperinsulinemic-hypoglycemic clamps in which the hypoglycemic nadir, 2.48 ± 0.06 mmol/l, was reached at a rate of decline in glucose of –0.09 or –0.21 mmol · l^–1 · min^–1 (PMV and control only). Additional PMV and control animals received an intravenous injection of the glucopenic agent 2-deoxyglucose.

RESULTS—Inducing hypoglycemia slowly, at a rate of –0.09 mmol · l^–1 · min^–1, resulted in a 26-fold increase in epinephrine (23.39 ± 0.62 nmol/l) and 12-fold increase in norepinephrine (11.42 ± 0.92 nmol/l) for controls (P < 0.001). The epinephrine response to hypoglycemia was suppressed by 91% in PMV (2.09 ± 0.07 nmol/l) vs. 61% in PV (9.05 ± 1.59 nmol/l) (P < 0.001). The norepinephrine response to hypoglycemia was suppressed by 94 and 80% in PMV and PV, respectively, compared with that in controls. In contrast, when arterial glucose was lowered to 2.49 ± 0.06 mmol/l within 20 min, no significant differences were observed in the catecholamine responses for PMV and controls over the first 45 min of hypoglycemia (20–65 min). Only at min 105 were catecholamines significantly lower for PMV vs. controls. Injection of 2-deoxyglucose induced a very rapid sympathoadrenal response with no significant differences between PMV and controls.

CONCLUSIONS—The critical locus for hypoglycemic detection shifts away from the portal-mesenteric vein to some other loci (e.g., the brain) when hypoglycemia develops rapidly.

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