Characterization of the portal signal in a nonsteady  hyperglycemic state in conscious dogs

Ogihara, Norikazu; Ebihara, Satoshi; Kawamura, Wataru; Okamoto, Mayumi; Sakai, Takako; Takiguchi, K.; Morita, Takasi; Uchida, Rie; Matsuyama, Yutaka; Hayashi, Yuzo; Arakawa, Yasuyuki; Kikuchi, Masatoshi

doi:10.1152/ajpendo.00079.2002

Cited by 7 publications

(9 citation statements)

References 18 publications

(19 reference statements)

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“…4) was similar to that achieved between NHGU and HGL in dogs (28). The slope of the regression lines of the net hepatic glycogen against the HGL axis was two times higher in Po than in Pe in rats, whereas that of NHGU was four times higher than Pe in dogs, with the intercepts on the HGL axis converging near the basal values in both animals.…”

Section: Discussionsupporting

confidence: 80%

“…This difference may be attributed, at least in part, to the difference in the experimental conditions. The A-P gradients were linearly related not only to hepatic glycogen synthesis in this study but also to NHGU in the previous study in dogs (28), whereas NHGU was saturated with increasing A-P gradients at greater than ϳ1 mmol in their study. The 80% replacement of Po by Pe achieved a comparable reduction in the A-P gradients in our study, whereas it evoked a lesser reduction in the A-P gradients in their study (31).…”

Section: Discussionsupporting

confidence: 64%

“…In the present study, HGL was calculated indirectly using the arterial glucose concentration to minimize any errors introduced by inadequacies in the mixing of blood and glucose in the portal vein. The indirect method was found to be more precise than the direct measurement in dogs (28). Furthermore, we measured the liver tissue glucose concentration directly to verify the indirect measurement of the HGL (Table 2).…”

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confidence: 95%

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Characterization of the portal signal during 24-h glucose delivery in unrestrained, conscious rats

Ogihara¹,

Kawamura²,

Kasuga³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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To characterize the "portal signal" during physiological glucose delivery, liver glycogen was measured in unrestrained rats during portal (Po) and peripheral (Pe) constant-rate infusion, with minimal differences in hepatic glucose load (HGL) and portal insulin between the delivery routes. Hepatic blood flows were measured by Doppler flowmetry during open surgery. Changes in hepatic glucose, portal insulin, glucagon, lactate, and free fatty acid concentrations were generally similar in either delivery except for glucagon at 4 h. Hepatic glycogen, however, increased continuously in Po and was higher than Pe at 8 and 24 h, although it decreased to the level of Pe upon the removal of Po at 8 h. There was a near-linear relationship between hepatic glycogen and HGL in either delivery, with the slope being twice as high in Po and the intercepts converging to basal HGL. The hepatic response to Po did not alter upon 80% replacement by Pe. These results suggest that negative arterial-portal glucose gradients increase the rate of hepatic glycogen synthesis against the incremental HGL in an all-or-nothing mode.hepatic glycogen synthesis; hepatic glucose load; negative arterialportal glucose gradients; nonsteady state IT HAS BEEN WELL DOCUMENTED that portal glucose delivery (Po) creates an important signal to enhance net hepatic glucose uptake (NHGU) or hepatic glycogen deposition in rodents (6, 9, 33), dogs (1-3, 14, 24, 25, 29 -31), and humans (8). Evidence has shown that NHGU is dependent on hepatic glucose load (HGL), plasma insulin concentration, and negative arterial-portal (A-P) glucose gradients. Adkins et al. (1) and have shown that a negative A-P gradient might serve as the portal signal, whereas Pagliassotti et al. (31) found that the magnitude of NHGU is dependent on the magnitude of the A-P gradients. On the other hand, Myers and colleagues (24,25) demonstrated that NHGU is linearly related to HGL, whereas it is curvilinearly related to the plasma insulin concentration, and that the hepatic response to Po results in a leftward shift in the dose-response relationship. These results have been obtained under hyperglycemic hyperinsulinemic and/or pancreatic clamp conditions, where the concentration of plasma glucose, that of insulin, or the negative A-P gradients were varied while the other two conditions were held fixed. Therefore, the relationship within these parameters remains unsettled in the nonsteady hyperglycemic state. Moore et al. (22) showed that, even in the absence of somatostatin and fixed hormone concentrations, the portal signal acts to stimulate NHGU during glucose infusion at a constant rate in dogs. In a similar experiment, we (28) also observed that there was a linear relationship between NHGU and HGL in either method of delivery, with the slope being four times steeper in Po and the HGL intercepts converging to near-basal values. We hypothesized from these results that the portal signal might increase the slope for NHGU against HGL.Therefore, the aim of the present study was to prove the hypo...

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 64%

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confidence: 95%

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Characterization of the portal signal during 24-h glucose delivery in unrestrained, conscious rats

Ogihara¹,

Kawamura²,

Kasuga³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…Previous reports suggested that some glucose sensors that can rapidly detect changes in glucose concentration are present in the brain (6,37,49), pancreatic islets (21,45), gut (45), and hepatoportal region (8,34,35). Recently, it has been demonstrated that postprandial secretion of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) could induce an early insulin response.…”

mentioning

confidence: 99%

“…It has been suggested that glucose sensors representing the hepatoportal region detect a glucose gradient between the portal vein and arterial blood (16,17,23) and stimulate glucose utilization and glycogen storage in the liver (34,35) during glucose perfusion into the portal vein, and that these responses are mediated by autonomic nerves. Guarino et al (20) also suggested that parasympathetic nerves in the liver control peripheral insulin sensitivity via an NO-dependent pathway.…”

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confidence: 99%

Mechanism of rapid-phase insulin response to elevation of portal glucose concentration

Fukaya¹,

Mizuno²,

Arai³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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The hepatoportal region is important for glucose sensing; however, the relationship between the hepatoportal glucose-sensing system and the postprandial rapid phase of the insulin response has been unclear. We examined whether a rapid-phase insulin response to low amounts of intraportal glucose infusion would occur, compared that with the response to intrajugular glucose infusion in conscious rats, and assessed whether this sensing system was associated with autonomic nerve activity. The increases in plasma glucose concentration did not differ between the two infusions at 3 min, but the rapid-phase insulin response was detected only in the intraportal infusion. A sharp and rapid insulin response was observed at 3 min after intraportal infusion of a small amount of glucose but not after intrajugular infusion. Furthermore, this insulin response was also induced by intraportal fructose infusion but not by nonmetabolizable sugars. The rapid-phase insulin response at 3 min during intraportal infusion did not differ between rats that had undergone hepatic vagotomy or chemical sympathectomy with 6-hydroxydopamine compared with control rats, but this response disappeared in rats that had undergone chemical vagotomy with atropine. We conclude that the elevation of glucose concentration in the hepatoportal region induced afferent signals from undetectable sensors and that these signals stimulate pancreas to induce the rapid-phase insulin response via cholinergic nerve action.

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Control of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves

Püschel

2004

Anat. Rec.

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More than any other organ, the liver contributes to maintaining metabolic equilibrium of the body, most importantly of glucose homeostasis. It can store or release large quantities of glucose according to changing demands. This homeostasis is controlled by circulating hormones and direct innervation of the liver by autonomous hepatic nerves. Sympathetic hepatic nerves can increase hepatic glucose output; they appear, however, to contribute little to the stimulation of hepatic glucose output under physiological conditions. Parasympathetic hepatic nerves potentiate the insulindependent hepatic glucose extraction when a portal glucose sensor detects prandial glucose delivery from the gut. In addition, they might coordinate the hepatic and extrahepatic glucose utilization to prevent hypoglycemia and, at the same time, warrant efficient disposal of excess glucose. Key words: glucose homeostasis; metabolic regulation; insulin sensitivityMore than any other organ, the liver contributes to the maintenance of the metabolic equilibrium of our body. Depending on the nutrient supply, it can shift from net glucose uptake and storage to net glucose output, thereby providing the energy source for those tissues that obligatorily depend on glucose. Liver also is a center of amino acid metabolism and ammonia detoxification, being unique in harboring the complete urea cycle. The rate of hepatic amino acid metabolization and urea formation varies widely, depending on the nutritional state. Besides the gut, the liver is the only organ that contains significant amounts of xanthinoxidase and thus can catalyze the last steps in purine catabolism. Liver is a key player in lipid metabolism, as it synthesizes and degrades lipoproteins and converts fatty acids to ketone bodies. In rodents but not normally in humans, it also synthesizes fatty acids from carbohydrates. Liver is an exocrine gland producing bile acids and it is the only significant site of cholesterol excretion. It is also the prime site of xenobiotic metabolism, chiefly allowing xenobiotic detoxification but also toxification. Finally, it is a control station of the hormone system; different hormones that control the intermediary metabolism are either degraded, activated, or synthesized in the liver. The metabolic pathways serving all these functions are tightly regulated and are subject to control by metabolite levels, circulating hormones, and hepatic nerves. The different levels of control are interrelated in many ways. This complex mode of regulation makes it difficult to discern the contribution of one particular branch of this control system. The role of hepatic nerves in the control of hepatic metabolism has often been disputed because no gross aberration of the metabolic homeostasis was observed when the nervous supply to the liver was interrupted by surgical or pharmacological means. However, although direct nervous control apparently contributes only subtle changes to the metabolic control in liver, it becomes increasingly evident that this fine tuning may ...

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Characterization of the portal signal in a nonsteady hyperglycemic state in conscious dogs

Cited by 7 publications

References 18 publications

Characterization of the portal signal during 24-h glucose delivery in unrestrained, conscious rats

Characterization of the portal signal during 24-h glucose delivery in unrestrained, conscious rats

Mechanism of rapid-phase insulin response to elevation of portal glucose concentration

Control of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves

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