Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice (original) (raw)
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Portal glucose infusion increases hepatic glycogen deposition in conscious unrestrained rats
Journal of Applied …, 1999
It has been demonstrated in the conscious dog that portal glucose infusion creates a signal that increases net hepatic glucose uptake and hepatic glycogen deposition. Experiments leading to an understanding of the mechanism by which this change occurs will be facilitated if this finding can be reproduced in the rat. Rats weighing 275-300 g were implanted with four indwelling catheters (one in the portal vein, one in the left carotid artery, and two in the right jugular vein) that were externalized between the scapulae. The rats were studied in a conscious, unrestrained condition 7 days after surgery, following a 24-h fast. Each experiment consisted of a 30-to 60-min equilibration, a 30-min baseline, and a 120-min test period. In the test period, a pancreatic clamp was performed by using somatostatin, insulin, and glucagon. Glucose was given simultaneously either through the jugular vein to clamp the arterial blood level at 220 mg/dl (Pe low group) or at 250 mg/dl (Pe high group), or via the hepatic portal vein (Po group; 6 mg•kg Ϫ1 •min Ϫ1) and the jugular vein to clamp the arterial blood glucose level to 220 mg/dl. In the test period, the arterial plasma glucagon and insulin levels were not significantly different in the three groups (36 Ϯ 2, 33 Ϯ 2, and 30 Ϯ 2 pg/ml and 1.34 Ϯ 0.08, 1.37 Ϯ 0.18, and 1.66 Ϯ 0.11 ng/ml in Po, Pe low, and Pe high groups, respectively). The arterial blood glucose levels during the test period were 224 Ϯ 4 mg/dl for Po, 220 Ϯ 3 for Pe low, and 255 Ϯ 2 for Pe high group. The liver glycogen content (µmol glucose/g liver) in the two Pe groups was not statistically different (51 Ϯ 7 and 65 Ϯ 8, respectively), whereas the glycogen level in the Po group was significantly greater (93 Ϯ 9, P Ͻ 0.05). Because portal glucose delivery also augments hepatic glycogen deposition in the rat, as it does in the dogs, mechanistic studies relating to its function can now be undertaken in this species. liver; somatostatin; insulin; glucagon; portal signal THE LIVER IS ONE OF THE KEY ORGANS in glucose homeostasis. Whereas a great deal is known about the liver as a producer of glucose, much less is known about its role in glucose disposal. It remains unclear exactly how hepatic glucose uptake is regulated after oral glucose consumption, when the blood glucose and insulin levels rise and the glucagon level falls. Based on work carried out in humans (11, 12) and in dogs (14, 18), it is clear that neither hyperinsulinemia nor hyperglycemia, when
Nonhepatic response to portal glucose delivery in conscious dogs
American Journal of …, 2000
The glycemic and hormonal responses and net hepatic and nonhepatic glucose uptakes were quantified in conscious 42-h-fasted dogs during a 180-min infusion of glucose at 10 mg· kg− 1· min− 1 via a peripheral (Pe10, n= 5) or the portal (Po10, n= 6) vein. ...
Journal of Clinical Investigation, 1987
To assess the importance of the route of glucose delivery in determining net hepatic glucose balance (NHGB) eight conscious overnight-fasted dogs were given glucose via the portal or a peripheral vein. NHGB was measured using the arteriovenous difference technique during a control and two 90-min glucose infusion periods. The sequence of infusions was randomized. Insulin and glucagon were held at constant basal levels using somatostatin and intraportal insulin and glucagon infusions during the control, portal, and peripheral glucose infusion periods (7±1, 7±1, 7±1 IU/ml; 100±3, 101±6, 101±3 pg/ml, respectively). In the three periods the hepatic blood flow, glucose infusion rate, arterial glucose level, hepatic glucose load, arterial-portal glucose difference and NHGB were 37±1, 34±1, 32±3 ml/kg per min; 0±0, 4.51±0.57, 4.23±0.34 mg/kg per min; 101±5, 200±15, 217±13 mg/dl; 28.5±3.5, 57.2±6.7, 54.0±6.4 mg/kg per min; +2±1,-22±3, +4±1 mg/dl; and 2.22±0.28,-1.41±031, and 0.08±0.23 mg/kg per min, respectively. Thus when glucose was delivered via a peripheral vein the liver did not take up glucose but when a similar glucose load was delivered intraportally the liver took up 32% (P < 0.01) of it. In conclusion portal glucose delivery provides a signal important for the normal hepatic-peripheral distribution of a glucose load. Methods Animals and surgical procedures. Experiments were carried out on eight overnight-fasted (18 h) conscious dogs (17-22 kg) of either sex that had Route ofGlucose Delivery and Hepatic Glucose Uptake 557 J. Clin. Invest.
Journal of Clinical Investigation, 1991
Although the importance of the hepatic glucose load in the regulation of liver glucose uptake has been clearly demonstrated in in vitro systems, the relationship between the hepatic glucose load and hepatic glucose uptake has yet to be defined in vivo. Likewise, the effects of the route of glucose delivery (peripheral or portal) on this relationship have not been explored. The aims of the present study were to determine the relationship between net hepatic glucose uptake (NHGU) and the hepatic glucose load in vivo and to examine the effects of the route of glucose delivery on this relationship. NHGU was evaluated at three different hepatic glucose loads in 42-h fasted, conscious dogs in both the absence (n = 7) and the presence (n = 6) of intraportal glucose delivery. In the abscence ofintraportal glucose delivery and in the presence of hepatic glucose loads of 50.5±5.9, 76.5±10.0, and 93.6±10.0 mg/kg/min and arterial insulin levels of-33 MU/ml, NHGU was 1.16±0.37, 2.78±0.82, and 5.07±1.20 mg/kg/min, respectively. When a portion of the glucose load was infused into the portal vein and similar arterial insulin levels (-36 juU/ml) and hepatic glucose loads (52.5±4.5, 70.4±5.6, and 103.6±18.4 mg/kg/min) were maintained, NHGU was twice that seen in the absence of portal loading (3.77±0.40, 4.80±0.59, and 9.62±1.43 mg/kg/ min, respectively). Thus, net hepatic glucose uptake demonstrated a direct dependence on the hepatic glucose load that did not reach saturation even at elevations in the hepatic glucose load of greater than three times basal. In addition, the presence of intraportal glucose delivery increased net hepatic glucose uptake apparently by lowering the threshold at which the liver switched from net glucose output to net glucose uptake. (J.
Glucose effectiveness is the major determinant of intravenous glucose tolerance in the rat
American Journal of Physiology Endocrinology and Metabolism, 1999
To determine the importance of insulin for glucose disposal during an intravenous glucose tolerance test in rats, experiments were performed in four cohorts of conscious unrestrained rats fasted overnight. In cohorts 1-3, a bolus of tracer ([3-3 H]glucose, 50 µCi) was given alone, with glucose (0.3 g/kg) to induce an endogenous insulin response (ϳ1,100 pmol/l), or with exogenous insulin to give physiological (1,700 pmol/l) or supraphysiological (12,000 pmol/l) plasma levels. Raising plasma insulin within the physiological range had no effect (P Ͼ 0.05), but supraphysiological levels induced hypoglycemia (7.3 Ϯ 0.2 to 3.6 Ϯ 0.2 mmol/l) and increased [ 3 H]glucose disappearance rate (P Ͻ 0.001). In cohort 4, a primed, continuous tracer infusion was started 120 min before saline or glucose bolus injection. [ 3 H]glucose levels fell 15-20%, and the disappearance rate rose 36% (P Ͻ 0.05) after glucose injection. These results indicate that in fasted rats a tracer bolus injection protocol is not sufficiently sensitive to measure the physiological effect of insulin released in response to a bolus of glucose because this effect of insulin is small. Glucose itself is the predominant mediator of glucose disposal after a bolus of glucose in the fasted rat. glucose tolerance test; insulin action; glucose disposal GLUCOSE TOLERANCE depends on three main factors: the circulating insulin level, the sensitivity of tissues to that insulin, and the effect of glucose itself to promote glucose uptake and to suppress hepatic glucose production (4). When plasma insulin is at basal levels, this effect of plasma glucose, termed ''glucose effectiveness,'' is the primary determinant of glucose disposal (1, 5, 14). Under nonbasal conditions, such as during an intravenous glucose tolerance test (IVGTT), when hyperglycemia evokes pancreatic insulin release, glucose disposal depends on both glucose effectiveness and the synergistic action of secreted insulin to suppress hepatic glucose production and to stimulate glucose uptake into insulin-sensitive tissues (muscle and fat) (4). Overall glucose homeostasis depends, therefore, on the interaction of the levels of insulin secretion, insulin action, and glucose effectiveness, and the development of glucose intolerance and type 2 diabetes may be influenced by each of these factors (5, 11, 29).
American journal of physiology. Endocrinology and metabolism, 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 approximately 16 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 (HALpo) received intraportal glucose (3.8 mg. kg-1. min-1) 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 (...