The locus for hypoglycemic detection shifts with the rate of fall in glycemia: the role of portal-superior mesenteric vein glucose sensing. Diabetes 2008;57:1380–1386

OBJECTIVE—To ascertain whether portal glucose sensing ex-tends 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 cannu-lated 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 l1 min1 (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 l1 min1, resulted in a 26-fold increase in epinephrin