Role of metabolic feedback regulation in glucose production of running rats

1988 ◽  
Vol 255 (3) ◽  
pp. R400-R406
Author(s):  
J. Vissing ◽  
B. Sonne ◽  
H. Galbo
Keyword(s):  
Hepatic Glucose Production ◽  
Feedback Regulation ◽  
Glucose Production ◽  
Central Command ◽  
Feedback Mechanisms ◽  
Fed State ◽  
Hepatic Glucose ◽  
Glucose Clearance ◽  
In Series ◽  
Exercise Induced

Hepatic glucose production (Ra) was studied in phlorizin (P)- and saline (C)-infused rats running for 35 min at 21 m/min in the postabsorptive state (series I) or 18 m/min in the fed state (series II). Phlorizin-induced increase in glucose clearance would increase or not affect Ra, depending on whether metabolic feedback mechanisms or central command from central nervous system (CNS), respectively, regulate Ra during exercise. Initial exercise-induced increases in Ra were similar in P and C rats of both series, although glucose clearance was higher and plasma glucose lower, however not hypoglycemic, in P rats. After 5 min of exercise, Ra remained similar in P and C rats in series I, whereas in series II, Ra increased almost twice as much in P compared with C rats. In both series muscle glycogenolysis and lipolysis were higher in P than in C rats. The results suggest a central command regulation of Ra from CNS motor centers and that this primary setting may be modulated by metabolic feedback mechanisms. Hypoglycemia is not needed to activate metabolic feedback. A variety of substrates rather than glucose specifically is mobilized by metabolic feedback mechanisms associated with decreased glucose availability.

Regulation of hepatic glucose production in running rats studied by glucose infusion

1988 ◽  
Vol 65 (6) ◽  
pp. 2552-2557 ◽  
Author(s):  
J. Vissing ◽  
B. Sonne ◽  
H. Galbo
Keyword(s):  
Feedforward Control ◽  
Feedback Inhibition ◽  
Hepatic Glucose Production ◽  
Plasma Catecholamines ◽  
Feedback Regulation ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Glucose Turnover ◽  
Hepatic Glucose ◽  
In Series

The importance of metabolic feedback regulation vs. feedforward regulation of hepatic glucose production (HGP) during exercise was investigated in rats by infusing glucose intravenously from the onset of running. Glucose infusion equaled the average exercise-induced increase from basal to steady state in HGP found in saline-infused control rats. Rats were studied at two work loads, running at 21 (series I) or 18 m/min (series II) for 35 min. Glucose turnover was measured by means of an intravenous [3H]glucose infusion. HGP was suppressed by glucose infusion corresponding to the infused amount of glucose in both series, except for late in exercise in series I, where HGP plus infused glucose tended to exceed HGP in saline-infused rats (P less than 0.10). Muscle glycogenolysis and fat metabolism were similar in both groups in the two series. Plasma glucose was never elevated, whereas insulin was, in glucose- vs. saline-infused rats of both series. Plasma catecholamines were lower in glucose- compared with saline-infused rats in series II. In conclusion, HGP is very sensitive to metabolic feedback inhibition at low exercise intensities. Feedforward control of HGP may play a role at higher work loads (series I). Exogenously supplied glucose, in moderate amounts, may replace HGP specifically without concomitant changes in mobilization of other substrates.

Effect of somatostatin on plasma glucagon and insulin, and glucose turnover in exercising sheep

1979 ◽  
Vol 47 (2) ◽  
pp. 273-278 ◽  
Author(s):  
R. P. Brockman
Keyword(s):  
Insulin Secretion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Strenuous Exercise ◽  
Glucose Turnover ◽  
Moderate Exercise ◽  
Plasma Glucagon ◽  
Hepatic Glucose ◽  
Exercise Induced ◽  
Glucagon And Insulin

To examine the roles of glucagon and insulin in exercise, four sheep were run on a treadmill with and without simultaneous infusion of somatostatin (SRIF), a peptide that suppresses glucagon and insulin secretion. SRIF infusion suppressed the exercise-induced rise in plasma glucagon during both moderate (5--5.5 km/h) and strenuous exercise (7.0 km/h). In addition, SRIF prevented the rise insulin concentrations during moderate exercise. During strenuous exercise, insulin concentrations were depressed in both groups. The infusion of SRIF was associated with a reduction in exercise-induced glucose production, as determined by infusion of [6–3H]glucose, during the first 15 min of both moderate and strenuous exercise compared to controls. Beyond 15 min glucose production was not significantly altered by SRIF infusions. These data are consistent with glucagon having an immediate, but only transient, stimulatory effect on the exercise-induced hepatic glucose production.

scholarly journals Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 102-113 ◽  
Author(s):  
Meena Garg ◽  
Manikkavasagar Thamotharan ◽  
Yun Dai ◽  
Venu Lagishetty ◽  
Aleksey V. Matveyenko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Caloric Restriction ◽  
Hepatic Glucose Production ◽  
Cell Mass ◽  
Glucose Production ◽  
Fatty Acid Transport ◽  
Β Cell ◽  
Hepatic Glucose ◽  
Glucose Clearance

Enhanced de novo lipogenesis (DNL), an adult hepatic adaption, is seen with high carbohydrate or low-fat diets. We hypothesized that ad libitum intake after prenatal calorie restriction will result in adult-onset glucose intolerance and enhanced DNL with modified lipid metabolic gene expression profile. Stable isotopes were used in 15-month-old adult male rat offspring exposed to prenatal (IUGR), pre- and postnatal (IPGR), or postnatal (PNGR) caloric restriction vs. controls (CON). IUGR vs. CON were heavier with hepatomegaly but unchanged visceral white adipose tissue (WAT), glucose intolerant with reduced glucose-stimulated insulin secretion (GSIS), pancreatic β-cell mass, and total glucose clearance rate but unsuppressed hepatic glucose production. Liver glucose transporter (Glut) 1 and DNL increased with decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase but increased WAT fatty acid transport protein-1 and peroxisomal proliferator-activated receptor-γ, resistin, and visfatin gene expression. In contrast, PNGR and IPGR were lighter, had reduced visceral WAT, and were glucose tolerant with unchanged hepatic glucose production but with increased GSIS, β-cell mass, glucose clearance rate, and WAT insulin receptor. Hepatic Glut1 and DNL were also increased in lean IPGR and PNGR with increased hepatic ACC, phosphorylated ACC, and pAMPK and reduced WAT fatty acid transport protein-1, peroxisomal proliferator-activated receptor-γ, and ACCα. We conclude the following: 1) the heavy, glucose-intolerant and insulin-resistant IUGR adult phenotype is ameliorated by postnatal caloric restriction; 2) increased DNL paralleling hepatic Glut1 is a biomarker of exposure to early caloric restriction rather than the adult metabolic status; 3) hepatic lipid enzyme expression reflects GSIS rather than DNL; and 4) WAT gene expression reflects an obesogenic vs. lean phenotype.

Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring

2006 ◽  
Vol 290 (6) ◽  
pp. E1218-E1226 ◽  
Author(s):  
Meena Garg ◽  
Manikkavasagar Thamotharan ◽  
Lisa Rogers ◽  
Sara Bassilian ◽  
W. N. Paul Lee ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Nutrient Restriction ◽  
Female Rat ◽  
Intrauterine Growth ◽  
Rat Offspring ◽  
Metabolic Adaptations ◽  
Hepatic Glucose ◽  
Glucose Clearance

We studied glucose metabolic adaptations in the intrauterine growth-restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), which is altered when there is imbalance between glucose production and utilization, was studied during a glucose tolerance test (GTT) in 2-day-old ( n = 8), 2-mo-old ( n = 22), and 15-mo-old ( n = 22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age), postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days, IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic glucose production and increased glucose disposal ( P < 0.01) compared with controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change. However, a decline in hepatic glucose-6-phosphatase ( P < 0.05) and fructose-1,6-biphosphatase ( P < 0.05) enzyme activities in the IUGR offspring was detected. At 15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain ( P < 0.01) and hyperinsulinemia ( P < 0.001) compared with postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient restriction (SM/SP) were smaller, hypoinsulinemic ( P < 0.03), and hypoleptinemic ( P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose clearance. We conclude that there is pre- and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype-specific manner.

Hepatic fuel metabolism during muscular work: role and regulation

1991 ◽  
Vol 260 (6) ◽  
pp. E811-E824 ◽  
Author(s):  
D. H. Wasserman ◽  
A. D. Cherrington
Keyword(s):  
Prolonged Exercise ◽  
Acid Metabolism ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Fat Oxidation ◽  
Nonesterified Fatty Acid ◽  
Fat Mobilization ◽  
Hepatic Glucose ◽  
Hepatic Fat ◽  
Exercise Induced

The increased fuel demands of the working muscle necessitate that metabolic processes within the liver be accelerated accordingly. The sum of changes in hepatic glycogenolysis and gluconeogenesis are closely coupled to the increase in glucose uptake by the working muscle, due to the actions of the pancreatic hormones. The exercise-induced rise in glucagon and fall in insulin interact to stimulate hepatic glycogenolysis, whereas the increase in gluconeogenesis is determined primarily by glucagon action. The increment in gluconeogenesis is caused by increases in hepatic gluconeogenic precursor delivery and fractional extraction as well as in the efficiency of intrahepatic conversion to glucose. Glucagon stimulates the latter two processes. Epinephrine may become important in the regulation of hepatic glucose production during prolonged or heavy exercise when its levels are particularly high. On the other hand, there is no evidence that hepatic innervation is essential for the rise in hepatic glucose production during exercise. Nonesterified fatty acid (NEFA) delivery to, uptake of, and oxidation by the liver are accelerated during prolonged exercise, resulting in an increase in ketogenesis. The rate of the first two of these processes is largely determined by factors that stimulate fat mobilization. The third step is regulated by both NEFA delivery to and glucagon-stimulated fat oxidation within the liver. The increase in hepatic fat oxidation produces energy that fuels gluconeogenesis. The shuttling of amino acids to the liver provides carbon-based compounds that are used for gluconeogenesis, transfers nitrogen to the liver, and supplies substrate for protein synthesis. During exercise, metabolic events within the liver, which are regulated by hormone levels and substrate supply, integrate pathways of carbohydrate, fat, and amino acid metabolism. These processes function to provide substrates for muscular energy metabolism and conserve carbon in glucose and nitrogen in protein.

Insulin action during fasting and refeeding in rat determined by euglycemic clamp

1985 ◽  
Vol 249 (5) ◽  
pp. E514-E518 ◽  
Author(s):  
L. Penicaud ◽  
J. Kande ◽  
J. Le Magnen ◽  
J. R. Girard
Keyword(s):  
Glucose Utilization ◽  
Blood Glucose Concentration ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Insulin Concentration ◽  
Hepatic Glucose ◽  
Glucose Clearance ◽  
Fasting And Refeeding ◽  
Fasted Rats

To further characterize the role of insulin in glucose metabolism during fasting and refeeding, euglycemic-hyperinsulinemic clamps were performed in control, 3 day-fasted, and 3 day-fasted then 3 day-refed rats. Glucose production and utilization were measured by using [3-3H]glucose. In control and refed rats, hepatic glucose production was totally suppressed at insulin concentration higher than 500 microU/ml; by contrast, during fasting, hepatic glucose production was not suppressed even at insulin concentration tenfold higher. Maximal increment of glucose utilization was lower in fasted than in control rats. Three days of refeeding restored almost entirely normal responses to insulin for glucose utilization. Blood glucose concentration was clamped at a different level in fasted and in control and refed rats; however, increment in glucose clearance in response to insulin was lower in fasted rats than in the two other groups. Thus fasting produces a state of insulin unresponsiveness both at the hepatic and peripheral levels, normal responsiveness being restored after 3 days of refeeding.

Effect of liver glycogen content on glucose production in running rats

1989 ◽  
Vol 66 (1) ◽  
pp. 318-322 ◽  
Author(s):  
J. Vissing ◽  
J. L. Wallace ◽  
H. Galbo
Keyword(s):  
Plasma Glucose ◽  
Glycogen Content ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Treadmill Running ◽  
Hepatic Glycogen ◽  
Hepatic Glucose ◽  
Exercise Induced

The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles.

Hepatic nerves are not essential to the increase in hepatic glucose production during muscular work

1990 ◽  
Vol 259 (2) ◽  
pp. E195-E203 ◽  
Author(s):  
D. H. Wasserman ◽  
P. E. Williams ◽  
D. B. Lacy ◽  
D. Bracy ◽  
A. D. Cherrington
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Hepatic Glucose ◽  
Exercise Induced ◽  
Glucagon And Insulin ◽  
Induced Changes ◽  
Hepatic Nerves ◽  
Rest And Exercise

To establish the role of hepatic nerves in hepatic glycogenolytic and gluconeogenic regulation during exercise, dogs underwent a laparotomy during which the hepatic nerves were either left intact (C; n = 8) or cut (DN; n = 5). At least 17 days after surgery, dogs were studied during 150 min of treadmill exercise (12% grade, 100 m/min). Glucose production (Ra) and gluconeogenesis (GNG) were assessed by combining [3-3H]glucose, [U-14C]alanine, and indocyanine green infusions with arterial, portal vein, and hepatic vein sampling. Glucagon and insulin were similar at rest and exercise in both groups. Norepinephrine rose from 145 +/- 10 to 242 +/- 32 pg/ml by 150 min of exercise in C and from 150 +/- 25 to 333 +/- 83 pg/ml in DN. Epinephrine rose from 66 +/- 7 pg/ml at rest to 108 +/- 10 and 148 +/- 24 pg/ml after 30 and 150 min of exercise in C and from 90 +/- 15 pg/ml at rest to 185 +/- 33 (P less than 0.05 compared with C) and 194 +/- 36 pg/ml after 30 and 150 min of exercise in DN. Plasma glucose fell gradually from 108 +/- 2 and 106 +/- 3 mg/dl at rest to 96 +/- 4 and 92 +/- 8 by the end of exercise in C and DN, respectively. Ra was similar in C and DN rising from 3.2 +/- 0.2 to 8.7 +/- 0.6 and 2.6 +/- 0.2 to 7.5 +/- 1.1 mg.kg-1.min-1, respectively, by the end of exercise. Minimum and maximum rates of GNG from alanine, glycerol, and lactate were elevated in DN compared with C during rest and exercise. However, the exercise-induced changes in GNG were similar in both groups. In conclusion, nerves to the liver are not essential to the increased Ra and glucose homeostasis during moderate-intensity exercise.

scholarly journals Role of Growth Hormone in Regulating Lipolysis, Proteolysis, and Hepatic Glucose Production during Fasting

2008 ◽  
Vol 93 (7) ◽  
pp. 2755-2759 ◽  
Author(s):  
Alla A. Sakharova ◽  
Jeffrey F. Horowitz ◽  
Sowmya Surya ◽  
Naila Goldenberg ◽  
Matthew P. Harber ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Open Label ◽  
Plasma Insulin Concentration ◽  
Fed State ◽  
Gh Secretion ◽  
Metabolic Role ◽  
Hepatic Glucose ◽  
Plasma Gh

Abstract Context: Fasting is associated with suppressed insulin and augmented GH secretion. The involvement of each mechanism in the regulation of fuel mobilization during fasting is unknown. Objective: To ascertain the role of GH in the regulation of the rates of lipolysis, proteolysis, and hepatic glucose production (HGP) during the physiological daily feed/fast cycle and after 2 d of complete fasting, we used a model of selective GH suppression by the administration of GHRH receptor antagonist (GHRH-A). Design and Setting: We conducted an open label in-patient study in the General Clinical Research Center at the University of Michigan. Participants: Six healthy, nonobese volunteers participated. Main Outcome Measures: We assessed 24-h plasma GH concentration and rates of lipolysis, proteolysis, and HGP using stable isotope techniques after an overnight fast and after 2 d of fasting. Results: GHRH-A suppressed plasma GH by about 65% during the fed state (P = 0.015) but did not alter the rates of lipolysis, proteolysis, or HGP. Fasting for 2 d suppressed plasma insulin concentration by about 80% and elevated plasma GH about 4-fold (both P &lt; 0.01). This was accompanied by a doubling in the rate of lipolysis, an approximately 40% increase in proteolysis, and an approximately 30% decline in HGP (all P &lt; 0.05). Preventing the fasting-induced increase in GH with GHRH-A largely abolished the increase in the rate of lipolysis. GHRH-A also augmented the fasting-induced reduction in HGP but did not alter proteolysis. Conclusions: Endogenous GH plays a very limited metabolic role during the daily feed/fast cycle but is essential for the increased lipolytic rate found with more prolonged fasting.

FoxO3 regulates hepatic glucose production

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
S Gul ◽  
KH Holzmann ◽  
F Leithäuser ◽  
H Maier ◽  
B Böhm ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose
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