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 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 x l(-1) x 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 x l(-1) x 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.