The Locus for Hypoglycemic Detection Shifts with the Rate of Fall in Glycemia: The Role of Portal-Superior Mesenteric Vein Glucose Sensing

Abstract

Objective: To ascertain whether “portal glucose sensing” extends beyond the portal vein to the superior-mesenteric vein, 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), portal and superior mesenteric veins (PMV), or sham operation (CON). One week later, animals underwent hyperinsulinemic-hypoglycemic clamps in which the hypoglycemic nadir, 2.48±0.06mmol/l, was reached at a rate of decline in glucose of −0.09 or –0.21 mM/min (PMV & CON only). Additional PMV and CON animals received an intravenous injection of the glucopenic agent 2-deoxyglucose.

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

Conclusion: 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.