Chronic hepatic artery ligation does not prevent liver from differentiating portal vs. peripheral glucose delivery

Abstract

Chronic hepatic artery ligation does not prevent liver from differentiating portal vs. peripheral glucose delivery. Am J Physiol Endocrinol Metab 285: E845-E853, 2003. First published May 28, 2003 10.1152/ajpendo.00130.2003.-Infusion of glucose into the hepatic artery blocks the stimulatory effect of the "portal signal" on net hepatic glucose uptake (NHGU) during portal glucose delivery. We hypothesized that hepatic artery ligation (HAL) would result in enhanced NHGU during peripheral glucose infusion because the arterial glucose concentration would be perceived as lower than that in the portal vein. Fourteen dogs underwent HAL ϳ16 days before study. Conscious 42-h-fasted dogs received somatostatin, intraportal insulin, and glucagon infusions at fourfold basal and at basal rates, respectively, and peripheral glucose infusion to create hyperglycemia. After 90 min (period 1), seven dogs (HAL po) received intraportal glucose (3.8 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and seven (HALpe) continued to receive only peripheral glucose for 90 min (period 2). These two groups were compared with nine non-HAL control dogs (control) treated as were HALpe. During period 2, the arterial plasma insulin concentrations (24 Ϯ 3, 20 Ϯ 1, and 24 Ϯ 2 U/ml) and hepatic glucose loads (39.1 Ϯ 2.5, 43.8 Ϯ 2.9, and 37.7 Ϯ 3.7 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were not different in HALpe, HAL po, and control, respectively. HALpo exhibited greater (P Ͻ 0.05) NHGU than HAL pe and control (3.1 Ϯ 0.3, 2.0 Ϯ 0.4, and 2.0 Ϯ 0.1 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , respectively). Net hepatic carbon retention was approximately twofold greater (P Ͻ 0.05) in HAL po than in HALpe and control. NHGU and net hepatic glycogen synthesis during peripheral glucose infusion were not enhanced by HAL. Even though there exists an intrahepatic arterial reference site for the portal vein glucose concentration, the failure of HAL to result in enhanced NHGU during peripheral glucose infusion suggests the existence of one or more comparison sites outside the liver. liver glucose uptake; portal vein NET HEPATIC GLUCOSE UPTAKE (NHGU) is enhanced approximately twofold when glucose is delivered via the hepatic portal vein vs. a peripheral vein (29,34). This "portal signal" appears to be neurally mediated (1). When glucose is delivered via the portal vein, the portal venous glucose concentration is greater than the glucose concentration in the arterial circulation, i.e., a negative arterial-portal (A-P) gradient exists. The rate of NHGU is related not to the portal vein glucose level per se (29) but instead to the magnitude of the negative A-P glucose gradient, up to approximately Ϫ18 mg/dl (35). This implies that the portal vein glucose concentration is compared with the arterial concentration at some site, triggering a neural response that includes enhancement of NHGU. The most likely reference sites for comparison with the portal vein glucose concentration would appear to be arteries perfusing the brain (specifically the hypothalamus; see Refs. 33 and 38), the carotid bodies (6,7,36), and the liver itself (14,4...

Hepatic portal venous delivery of a nitric oxide synthase inhibitor enhances net hepatic glucose uptake

“…Suppression of hepatic arterial flow results in shunting of blood away from the sinusoids, where most glucose uptake takes place, and toward the hepatic vein (1). Complete occlusion or ligation of the hepatic artery reduces liver glucose uptake in vitro (1) and in vivo (24). Conversely, intraportal delivery of acetylcholine, which increased hepatic artery blood flow more than twofold but did not alter portal vein blood flow, enhanced NHGU 70% under hyperglycemic hyperinsulinemic conditions (35).…”

Intraportal administration of neuropeptide Y and hepatic glucose metabolism

“…Thus, there was no evidence of a vasoconstrictive effect of NPY in our studies. Moreover, if significant vasoconstriction had occurred, it would likely have blunted, rather than enhanced, NHGU (4,25).…”