Modulation of glucose metabolic response to endotoxin by granulocyte colony-stimulating factor

1992 ◽  
Vol 263 (5) ◽  
pp. R1122-R1129
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
C. Dobrescu ◽  
S. Nelson ◽  
J. J. Spitzer
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Metabolic Response ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Lps Challenge ◽  
Stimulating Factor

The present study examines whether in vivo administration of granulocyte colony-stimulating factor (G-CSF) and the resultant neutrophilia alters basal glucose metabolism or modulates the glucose metabolic response to a subsequent endotoxin [lipopolysaccharide (LPS)] challenge. Rats were injected with human recombinant G-CSF (50 micrograms/kg sc) twice daily for 2 days preceding an injection of LPS. Animals treated with G-CSF showed an eightfold increase in blood polymorphonuclear leukocytes (PMNs) but no detectable changes in hemodynamics or glucose metabolism. In control animals, LPS transiently decreased circulating PMN number, but by 4 h neutrophils had returned to control levels. LPS produced a greater reduction in circulating neutrophils in G-CSF-treated animals, which did not return to pretreatment levels by 4 h. G-CSF also produced marked changes in the glucose metabolic response to LPS. Rates of whole body glucose production and utilization in both control and G-CSF-treated rats were rapidly increased by LPS; however, the increment in glucose flux was 55-100% greater in the latter group. The enhanced rate of hepatic glucose production in this group occurred despite lower plasma levels of lactate and glucagon. The elevated rate of whole body glucose utilization was attributable to the G-CSF-enhanced LPS-induced increase in glucose uptake by the ileum, spleen, liver, and lung. Furthermore, LPS increased glucose uptake by skeletal muscle in G-CSF-treated rats but not in control animals. The enhanced glucose disposal in G-CSF-treated rats was not mediated by increases in plasma glucose or insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Importance of the route of insulin delivery to its control of glucose metabolism

2021 ◽  
Author(s):  
Dale S. Edgerton ◽  
Mary Courtney Moore ◽  
Justin M. Gregory ◽  
Guillaume Kraft ◽  
Alan D. Cherrington
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
The Body ◽  
Whole Body ◽  
Direct Effects ◽  
Pancreatic Insulin ◽  
Hepatic Glucose

Pancreatic insulin secretion produces an insulin gradient at the liver compared to the rest of the body (approximately 3:1). This physiologic distribution is lost when insulin is injected subcutaneously, causing impaired regulation of hepatic glucose production and whole body glucose uptake, as well as arterial hyperinsulinemia. Thus, the hepatoportal insulin gradient is essential to the normal control of glucose metabolism during both fasting and feeding. Insulin can regulate hepatic glucose production and uptake through multiple mechanisms, but its direct effects on the liver are dominant under physiologic conditions. Given the complications associated with iatrogenic hyperinsulinemia in patients treated with insulin, insulin designed to preferentially target the liver may have therapeutic advantages.

Intraportal administration of neuropeptide Y and hepatic glucose metabolism

2008 ◽  
Vol 294 (4) ◽  
pp. R1197-R1204 ◽  
Author(s):  
Makoto Nishizawa ◽  
Masakazu Shiota ◽  
Mary Courtney Moore ◽  
Stephanie M. Gustavson ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Neuropeptide Y ◽  
Glucose Uptake ◽  
Infusion Rate ◽  
Whole Body ◽  
Glucose Disposal ◽  
Control Group ◽  
Intravenous Glucose ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

We examined whether intraportal delivery of neuropeptide Y (NPY) affects glucose metabolism in 42-h-fasted conscious dogs using arteriovenous difference methodology. The experimental period was divided into three subperiods (P1, P2, and P3). During all subperiods, the dogs received infusions of somatostatin, intraportal insulin (threefold basal), intraportal glucagon (basal), and peripheral intravenous glucose to increase the hepatic glucose load twofold basal. Following P1, in the NPY group ( n = 7), NPY was infused intraportally at 0.2 and 5.1 pmol·kg−1·min−1 during P2 and P3, respectively. The control group ( n = 7) received intraportal saline infusion without NPY. There were no significant changes in hepatic blood flow in NPY vs. control. The lower infusion rate of NPY (P2) did not enhance net hepatic glucose uptake. During P3, the increment in net hepatic glucose uptake (compared with P1) was 4 ± 1 and 10 ± 2 μmol·kg−1·min−1 in control and NPY, respectively ( P < 0.05). The increment in net hepatic fractional glucose extraction during P3 was 0.015 ± 0.005 and 0.039 ± 0.008 in control and NPY, respectively ( P < 0.05). Net hepatic carbon retention was enhanced in NPY vs. control (22 ± 2 vs. 14 ± 2 μmol·kg−1·min−1, P < 0.05). There were no significant differences between groups in the total glucose infusion rate. Thus, intraportal NPY stimulates net hepatic glucose uptake without significantly altering whole body glucose disposal in dogs.

scholarly journals Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 459-471 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Endogenous Glucose

1. The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure.2. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose.3. From the resultinginsulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants.4. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P < 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant.5. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively.6. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively.7. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

scholarly journals Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2163-2168 ◽  
Author(s):  
Y Kawase ◽  
M Akashi ◽  
H Ohtsu ◽  
Y Aoki ◽  
A Akanuma ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Whole Body ◽  
Leukemia Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Myeloid Leukemias ◽  
Fab Classification ◽  
Radiation Induced ◽  
Stimulating Factor

Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimulates proliferation of myeloid leukemia cells as well as normal granulocytes in vitro. We designed a method to determine if G-CSF affects the incidence of myeloid leukemias induced by irradiation and the types of leukemias induced according to the French-American-British (FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2 micrograms/d for 7 days) after a single 3-Gy irradiation significantly increased the number of peripheral blood neutrophils as compared with those in control mice. Even after discontinuation of G-CSF, both the total leukocyte and neutrophil counts increased to day 10, and their levels remained elevated until day 14. The incidence of myeloid leukemia in mice exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice with radiation-induced leukemia, those receiving G- CSF had a mean survival time of 357 days, whereas those not receiving the factor survived for 349 days. There was no significant difference of survivals between the two groups. Most of the radiation-induced leukemias in the two groups were M1 or M2, according to the FAB classification; no characteristic difference was observed among the types of leukemias. Although G-CSF stimulated the leukemia cells in vitro, G-CSF administration after irradiation did not increase the occurrence of radiation-induced myeloid leukemias. Our results show that administration of G-CSF effectively accelerates neutrophil recovery from irradiation-induced hematopoietic injury and does not enhance the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.

Glucose-fatty acid interactions in prepubertal and pubertal children: effects of lipid infusion

1997 ◽  
Vol 272 (4) ◽  
pp. E523-E529 ◽  
Author(s):  
S. Arslanian ◽  
C. Suprasongsin
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Healthy Children ◽  
Prepubertal Children ◽  
Tissue Sensitivity

This investigation examined whether puberty differs from prepuberty in regard to the effects of increased free fatty acid (FFA) on in vivo glucose metabolism. Nine prepubertal and 13 pubertal healthy children were studied. Each subject was studied twice, once with 0.9% sodium chloride solution (control study) and once with 20% Intralipid infusion in the basal state and during a 3-h hyperinsulinemic-euglycemic clamp, with [6,6-2H2]glucose tracer. During control studies, prepubertal children had lower basal fat oxidation and higher insulin-mediated glucose disposal than pubertal adolescents. During Intralipid infusion, basal glucose uptake increased in prepubertal children but did not change in pubertal adolescents. Insulin-stimulated whole body glucose disposal did not change in prepubertal children (control 77.6 +/- 8.9, Intralipid 84.5 +/- 13.3 micromol x kg(-1) x min(-1)) but decreased in pubertal adolescents (control 55.0 +/- 3.6, Intralipid 46.7 +/- 3.4 micromol x kg(-1) x min(-1), P = 0.01) despite comparable decrements in glucose oxidaion. We conclude that in prepubertal children lipids exert effects in the basal state by stimulating hepatic glucose production and glucose disposal, whereas in pubertal adolescents they induce peripheral tissue insulin resistance by decreasing insulin-stimulated glucose uptake. This differential response could be due to developmental-maturational changes in tissue sensitivity and/or specificity to the glucose-FFA interaction.

Epinephrine-induced changes in hepatic glucose production after ethanol

1994 ◽  
Vol 266 (6) ◽  
pp. E863-E869
Author(s):  
C. H. Lang ◽  
P. E. Molina ◽  
N. Skrepnick ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Response ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Plasma Catecholamines ◽  
Glucose Production ◽  
Whole Body ◽  
Metabolic Clearance ◽  
Hepatic Glucose ◽  
Acute Ethanol

Previous studies indicate that catecholamines play an important role in mediating the glucose metabolic response to endotoxin. Because acute ethanol (EtOH) intoxication impairs this response, the present study was initiated to ascertain whether EtOH attenuates the lipopolysaccharide response by decreasing the increment in plasma catecholamines after endotoxin or by decreasing the responsiveness of rats to epinephrine. All studies were performed on chronically catheterized fasted rats infused intravenously with either EtOH or an equal volume of saline. In the first series of experiments, intravenous administration of Escherichia coli endotoxin increased, to the same extent, the plasma concentrations of epinephrine and norepinephrine in both saline- and EtOH-infused rats. In the second study, rats were infused with [3-3H]glucose to assess whole body glucose metabolism and the ability of EtOH to alter the glucose metabolic response to epinephrine. The exogenous infusion of a maximally stimulating dose of epinephrine (1 microgram.min-1.kg-1) into saline-infused control animals for 3 h produced a marked hyperglycemia that resulted from a sustained increase in the rate of hepatic glucose production and a reduction in the metabolic clearance rate for glucose. EtOH infusion did not prevent the epinephrine-induced hyperglycemia but blunted the stimulatory effect of epinephrine on glucose production. The differences in glucose metabolism between saline- and EtOH-treated rats could not be explained by changes in plasma insulin or glucagon concentrations. Furthermore, the ability of EtOH to impair the epinephrine-induced increase in glucose production was still evident in rats treated with 4-methylpyrazole, an inhibitor of alcohol dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy

2006 ◽  
Vol 290 (2) ◽  
pp. E289-E298 ◽  
Author(s):  
C. Hadigan ◽  
D. Kamin ◽  
J. Liebau ◽  
S. Mazza ◽  
S. Barrow ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Subcutaneous Fat ◽  
Fat Distribution ◽  
Whole Body ◽  
Glucose Disposal ◽  
Positron Emission ◽  
Specific Regulation ◽  
Hiv Lipodystrophy

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU·m−2·min−1) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-d-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 ± 0.4 vs. 2.3 ± 0.5 μmol·kg tissue−1·min−1, P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal ( r2 = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area ( r = −0.75, P = 0.008), and whole body glucose disposal ( r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.

scholarly journals Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2163-2168 ◽  
Author(s):  
Y Kawase ◽  
M Akashi ◽  
H Ohtsu ◽  
Y Aoki ◽  
A Akanuma ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Whole Body ◽  
Leukemia Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Myeloid Leukemias ◽  
Fab Classification ◽  
Radiation Induced ◽  
Stimulating Factor

Abstract Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimulates proliferation of myeloid leukemia cells as well as normal granulocytes in vitro. We designed a method to determine if G-CSF affects the incidence of myeloid leukemias induced by irradiation and the types of leukemias induced according to the French-American-British (FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2 micrograms/d for 7 days) after a single 3-Gy irradiation significantly increased the number of peripheral blood neutrophils as compared with those in control mice. Even after discontinuation of G-CSF, both the total leukocyte and neutrophil counts increased to day 10, and their levels remained elevated until day 14. The incidence of myeloid leukemia in mice exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice with radiation-induced leukemia, those receiving G- CSF had a mean survival time of 357 days, whereas those not receiving the factor survived for 349 days. There was no significant difference of survivals between the two groups. Most of the radiation-induced leukemias in the two groups were M1 or M2, according to the FAB classification; no characteristic difference was observed among the types of leukemias. Although G-CSF stimulated the leukemia cells in vitro, G-CSF administration after irradiation did not increase the occurrence of radiation-induced myeloid leukemias. Our results show that administration of G-CSF effectively accelerates neutrophil recovery from irradiation-induced hematopoietic injury and does not enhance the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.

Exercise-induced fall in insulin: mechanism of action at the liver and effects on muscle glucose metabolism

1994 ◽  
Vol 266 (5) ◽  
pp. E683-E689 ◽  
Author(s):  
B. A. Zinker ◽  
T. Mohr ◽  
P. Kelly ◽  
K. Namdaran ◽  
D. P. Bracy ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Femoral Vein ◽  
Vena Cava ◽  
External Iliac Artery ◽  
Glucose Production ◽  
Whole Body ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Exercise Induced

To determine the importance of the fall in insulin on whole body glucose fluxes and muscle glucose metabolism during exercise, dogs ran on a motorized treadmill for 90 min at a moderate work rate with somatostatin (SRIF) infused to suppress insulin and glucagon and basal (B-INS; n = 6 dogs) or exercise-stimulated (S-INS; n = 8 dogs) insulin replacement. The fall in insulin during exercise potently stimulates glucose production at least in part by potentiating the actions of glucagon. To assess the hepatic effects of insulin in the absence of its potentiating effect on glucagon action, glucagon levels were not restored during SRIF infusion. At least 17 days before experimentation, dogs underwent surgery for chronic placement of sampling (carotid artery and femoral vein) and infusion (inferior vena cava and portal vein) catheters. Hindlimb blood flow was assessed by placement of a Doppler flow cuff on the external iliac artery. Whole body glucose production (Ra) and disappearance (Rd) were assessed with [3-3H]glucose, and hindlimb glucose uptake and metabolism were assessed with arterial-venous differences and [U-14C]glucose. Insulin levels were 69 +/- 6 and 61 +/- 7 pM at rest in B-INS and S-INS and 62 +/- 10 and 41 +/- 6 pM at 30 min of exercise. Glucose levels were clamped at euglycemic levels with an exogenous glucose infusion during rest and exercise in both groups. Exercise-induced increases in Ra, Rd, hindlimb glucose uptake, and hindlimb oxidative and nonoxidative glucose metabolism were not affected by maintenance of basil insulin levels during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

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