NOVEL GLUCOSENSOR FOR HYPOGLYCEMIC DETECTION LOCALIZED TO THE PORTAL-VEIN

In this investigation, we sought to constrain the locus of essential p ortohepatic glucosensors and test the hypothesis that they reside stri ctly in the portal vein and not the liver. Male Wistar rats were chron ically cannulated in the carotid artery (sampling), jugular vein (infu sion), and portal vein, either adjacent to (PORADJ, 0.6 +/- 0.1 cm, n = 6) or upstream from (PORUPS, 2.7 +/- 0.1 cm, n = 8) the liver. Anima ls were exposed to one of three protocols distinguished by the site of glucose infusion: PORUPS, PORADJ, or peripheral (PER). Systemic hypog lycemia (2.4 +/- 0.1 mmol/l) was induced via jugular vein insulin infu sion (50 mU.kg(-1).min(-1)). Arterial plasma catecholamines were asses sed at basal (-30 and 0 min) and during sustained hypoglycemia (60, 75 , 90, 105 min). By design, hepatic glucose was significantly elevated during PORUPS and PORADJ versus PER (4.3 +/- 0.1 vs. 2.4 +/- 0.1 mmol/ l, respectively; P < 0.05). There mere no significant differences betw een protocols in arterial glucose or insulin concentrations (9,372 +/- 1,798 pmol/l). When liver and systemic glucose concentrations were al lowed to fall concomitantly (PER), epinephrine was elevated 16-fold ab ove basal levels (3.0 +/- 0.6 vs. 46.4 +/- 4.3 nmol/l, P < 0.001). Whe n portohepatic normoglycemia was maintained during PORUPS, a 67% suppr ession in the epinephrine response versus that during PER was observed (P < 0.001). However, when the cannula was advanced adjacent to the l iver, by comparison with PER, there was no suppression in the sympatho adrenal response (P = 0.73). While both PORUPS and PORADJ yielded elev ated liver glycemia in the face of systemic hypoglycemia, only PORUPS yielded an elevated portal vein glucose concentration. That only PORUP S resulted in a significant suppression of the sympathoadrenal respons e is consistent with the localization of the glucosensors to the porta l vein.