The locus for hypoglycemic detection shifts with the rate of fall in glycemia: the role of portal-superior mesenteric vein glucose sensing.
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.


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.
Saberi
Maziyar
M
University of Southern California, Department of Kinesiology, Los Angeles, CA 90089-0652, USA.
Bohland
MaryAnn
M
Donovan
Casey M
CM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D003847:Deoxyglucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000503:physiopathology; D007003:Hypoglycemia / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008642:Mesenteric Veins / Q000503:physiopathology*; D011169:Portal Vein / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D003847:Deoxyglucose; D015740:Calcitonin Gene-Related Peptide