Indomethacin Stimulates Basal Glucose Production in Humans without Changes in Concentrations of Glucoregulatory Hormones

1993 ◽  
Vol 85 (6) ◽  
pp. 679-685 ◽  
Author(s):  
E. P. M. Corssmit ◽  
J. A. Romijn ◽  
E. Endert ◽  
H. P. Sauerwein
Keyword(s):  
Continuous Infusion ◽  
Control Experiment ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
C Peptide ◽  
Hepatic Glucose ◽  
Glucoregulatory Hormones

1. To investigate whether indomethacin affects basal glucose production, we measured hepatic glucose production in six healthy postabsorptive subjects on two occasions: once after administration of indomethacin (150 mg orally) and once after administration of placebo. 2. Glucose production was measured by primed, continuous infusion of [3-3H]-glucose. 3. Indomethacin administration resulted in an increase in glucose production from 10.9 (SEM 0.3) μmol min−1 kg−1 to a maximum of 16.5 (SEM 1.6) μmol min−1 kg−1 (P <0.05) within ∼1 h, whereas in the control experiment glucose production declined gradually (P <0.01) (P <0.05 indomethacin versus control). There were no differences in plasma concentrations of insulin, C-peptide and counter-regulatory hormones between the two experiments. 4. Since indomethacin administration resulted in an increase in glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclude that indomethacin stimulates hepatic glucose production through other mechanisms.

Pentoxifylline inhibits basal glucose production in humans

1994 ◽  
Vol 77 (6) ◽  
pp. 2767-2772 ◽  
Author(s):  
E. P. Corssmit ◽  
J. A. Romijn ◽  
E. Endert ◽  
H. P. Sauerwein
Keyword(s):  
Continuous Infusion ◽  
Adenosine Receptor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Volume Of Distribution ◽  
Time Interval ◽  
Xanthine Derivative ◽  
Hepatic Glucose ◽  
Glucoregulatory Hormones

Adenosine stimulates hepatic glucose production in vitro. To investigate whether pentoxifylline, a xanthine derivative that blocks the adenosine receptor, inhibits basal glucose production, we measured hepatic glucose production in eight healthy postabsorptive subjects on two occasions: during continuous infusion of pentoxifylline and, in a control study, during saline infusion. Glucose production was measured by primed continuous infusion of [3–3H]glucose. Pentoxifylline infusion resulted in an approximately 22 (volume of distribution for glucose 40 ml/kg) to approximately 46% (volume of distribution for glucose 165 ml/kg) decrease in basal glucose production within approximately 1 h (P < 0.05), whereas in the control experiment glucose production declined by only approximately 4% in this time interval (P < 0.03 pentoxifylline vs. control). There were no differences in concentrations of insulin, C peptide, glucagon, or catecholamines between the two experiments. Because pentoxifylline inhibited glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclude that pentoxyifylline inhibits hepatic glucose production through other mechanisms, e.g., by blocking the adenosine receptor.

scholarly journals Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hepatic Glucose ◽  
Molar Percent ◽  
Glucose Output

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.

Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase

1993 ◽  
Vol 264 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
L. Rossetti ◽  
S. Farrace ◽  
S. B. Choi ◽  
A. Giaccari ◽  
L. Sloan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Intracellular Glucose

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is released at the neuromuscular junction in response to nerve excitation. To examine the relationship between plasma CGRP concentration and intracellular glucose metabolism in conscious rats, we performed insulin (22 pmol.kg-1.min-1) clamp studies combined with the infusion of 0, 20, 50, 100, 200, and 500 pmol.kg-1.min-1 CGRP (plasma concentrations ranging from 2 x 10(-11) to 5 x 10(-9) M). CGRP antagonized insulin's suppression of hepatic glucose production at plasma concentrations (approximately 10(-10) M) that are only two- to fivefold its basal portal concentration. Insulin-mediated glucose disposal was decreased by 20-32% when CGRP was infused at 50 pmol.kg-1.min-1 (plasma concentration 3 x 10(-10) M) or more. The impairment in insulin-stimulated glycogen synthesis in skeletal muscle accounted for all of the CGRP-induced decrease in glucose disposal, while whole body glycolysis was increased despite the reduction in total glucose uptake. The muscle glucose 6-phosphate concentration progressively increased during the CGRP infusions. CGRP inhibited insulin-stimulated glycogen synthase in skeletal muscle with a 50% effective dose of 1.9 +/- 0.36 x 10(-10) M. This effect on glycogen synthase was due to a reduction in enzyme affinity for UDP-glucose, with no changes in the maximal velocity. In vitro CGRP stimulated both hepatic and skeletal muscle adenylate cyclase in a dose-dependent manner. These data suggest that 1) CGRP is a potent antagonist of insulin at the level of muscle glycogen synthesis and hepatic glucose production; 2) inhibition of glycogen synthase is its major biochemical action in skeletal muscle; and 3) these effects are present at concentrations of the peptide that may be in the physiological range for portal vein and skeletal muscle. These data underscore the potential role of CGRP in the physiological modulation of intracellular glucose metabolism.

Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans

1989 ◽  
Vol 257 (2) ◽  
pp. E241-E246 ◽  
Author(s):  
L. Luzi ◽  
R. A. DeFronzo
Keyword(s):  
Insulin Secretion ◽  
Insulin Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Second Phase ◽  
C Peptide ◽  
Hyperglycemic Clamp ◽  
Study Protocols ◽  
Hepatic Glucose ◽  
First Phase Insulin Secretion

To examine the importance of first-phase insulin secretion on total body glucose homeostasis, six normal subjects (age, 24 +/- 1 yr; ideal body wt, 100 +/- 1%) received three hyperglycemic (+75 mg/100 ml) clamp studies in combination with [3-3H]glucose: study I, 150 min hyperglycemic clamp; study II, hyperglycemic clamp plus somatostatin (6 micrograms/min) plus basal glucagon replacement (0.4 ng.kg-1.min-1) plus an insulin infusion designed to mimic only the second phase of insulin secretion; and study III, hyperglycemic clamp plus somatostatin plus basal glucagon plus an insulin infusion designed to mimic both the first and second phase of insulin secretion. Basal plasma C-peptide concentrations averaged 0.21 +/- 0.01 pmol/ml in the three study protocols. In study I the plasma C-peptide response demonstrated an early burst within the first 10 min followed by a gradually increasing phase of C-peptide secretion that lasted until the end of the study. In studies II and III plasma C-peptide declined within the first 10 min after somatostatin was started and averaged 0.06 +/- 0.01 and 0.05 +/- 0.01 pmol/min, respectively. Basal hepatic glucose production (2.3 +/- 0.2 mg.kg-1.min-1) was suppressed by 90% at 20 min and remained suppressed thereafter in studies I and III. In contrast, in study II hepatic glucose production was inhibited by only 50% (1.1 +/- 0.2 mg.kg-1.min-1) at 60 min (P less than 0.01 vs. studies I and III) and remained incompletely suppressed even after 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose production during exercise in humans: a-hv balance and isotopic-tracer measurements compared

1999 ◽  
Vol 87 (1) ◽  
pp. 111-115 ◽  
Author(s):  
R. Bergeron ◽  
M. Kjaer ◽  
L. Simonsen ◽  
J. Bülow ◽  
H. Galbo
Keyword(s):  
Blood Flow ◽  
Continuous Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Dilution Method ◽  
Hepatic Glucose ◽  
Balance Technique ◽  
Tracer Dilution ◽  
Exercise In Humans

The present study compared the arteriohepatic venous (a-hv) balance technique and the tracer-dilution method for estimation of hepatic glucose production during both moderate and heavy exercise in humans. Eight healthy young men (aged 25 yr; range, 23–30 yr) performed semisupine cycling for 40 min at 50.4 ± 1.5(SE)% maximal O2 consumption, followed by 30 min at 69.0 ± 2.2% maximal O2 consumption. The splanchnic blood flow was estimated by continuous infusion of indocyanine green, and net splanchnic glucose output was calculated as the product of splanchnic blood flow and a-hv blood glucose concentration differences. Glucose appearance rate was determined by a primed, continuous infusion of [3-3H]glucose and was calculated by using formulas for a modified single compartment in non-steady state. Glucose production was similar whether determined by the a-hv balance technique or by the tracer-dilution method, both at rest and during moderate and intense exercise ( P > 0.05). It is concluded that, during exercise in humans, determination of hepatic glucose production can be performed equally well with the two techniques.

Women at altitude: changes in carbohydrate metabolism at 4,300-m elevation and across the menstrual cycle

1998 ◽  
Vol 85 (5) ◽  
pp. 1966-1973 ◽  
Author(s):  
Barry Braun ◽  
Gail E. Butterfield ◽  
Shannon B. Dominick ◽  
Stacy Zamudio ◽  
Rosann G. McCullough ◽  
...  
Keyword(s):  
High Altitude ◽  
Plasma Insulin ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Ovarian Hormones ◽  
Glucose Response ◽  
C Peptide ◽  
High Carbohydrate ◽  
Hepatic Glucose ◽  
Stimulation Of

We hypothesized that, in women, the blood glucose response to a meal (BGR) would be lower after exposure to 4,300 m compared with sea level (SL) and that BGR would be reduced in the presence of estrogen plus progesterone (E+P) relative to estrogen alone (E). Sixteen women were studied in both the E and E+P conditions at SL and in either the E or E+P condition at 4,300 m. On day 9 in each condition, blood was sampled before, and every 30 min for 2 h after, the subjects ate a high-carbohydrate meal. At 4,300 m, BGR peaked at a lower value (5.73 ± 0.94 mM) than at SL (6.44 ± 1.45 mM) and returned to baseline more slowly ( P < 0.05). Plasma insulin values were the same but C peptide was slightly higher at 4,300 m ( P < 0.05). At SL, BGR returned to baseline more slowly in E+P condition (5.13 ± 0.89 and 5.21 ± 0.91 mM at 60 and 90 min, respectively) relative to E condition (4.51 ± 0.52 and 4.69 ± 0.88 mM, respectively) ( P < 0.05). Insulin and C peptide were not different between E and E+P conditions. The data indicate that BGR is lower in women at high altitude compared with the SL, possibly due to greater suppression of hepatic glucose production or stimulation of peripheral glucose uptake by insulin. BGR was lower in E condition relative to E+P condition at SL and possibly at 4,300 m, but the relative concentrations of ovarian hormones do not appear to alter the magnitude of the change in BGR when women are exposed to high altitude.

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