Interrelationship of FFA and glycerol turnovers in resting and exercising dogs

1975 ◽  
Vol 39 (1) ◽  
pp. 30-36 ◽  
Author(s):  
W. A. Shaw ◽  
T. B. Issekutz ◽  
B. Issekutz
Keyword(s):  
Plasma Concentrations ◽  
Hepatic Glucose Output ◽  
Experimental Conditions ◽  
Straight Line ◽  
Wide Range ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
The Given

Dogs with indwelling arterial and venous catheters ran on a treadmill on a 10% or on a 15% slope at 100 m/min. Glycerol turnover ([2–3H]-glycerol) and FFA turnover ([1–14C]palmitate) were measured simultaneously. Both turnovers were greatly increased by exercise. Similar increases were produced in resting dogs by norepinephrine infusions (0.5 mug/kg-min). At rest, as well as during exercise, there was a straight-line correlation between the ratio of disappearance of each substrate and their respective plasma concentrations. Over a wide range there was a straight-line correlation between the rate of production of FFA (RaFFA) and that of glycerol (RaGLY) at rest as well as during exercise. At any given RaFFA, RaGLY was higher in the running than in the resting dog. At rest the ratio of RaFFA/RaGLY was found to give the theoretical value of 3.0 only when RaFFA was 10–15 mumol/kg-min, below this the ratio was lower and above this it was higher. During exercise the ratio was lower than at rest and at heavier load lower than at lighter work. The results suggest that in vivo a combination of partial and complete lipolysis as well as reesterification occurs. The glucose equivalent of the glycerol turnover (if 100% converted) represents (under the given experimental conditions) 14–18% of the hepatic glucose output on the 15% slope and 20–25% of it on the 10% slope.

scholarly journals Autoregulation of hepatic glucose production

1998 ◽  
pp. 240-248 ◽  
Author(s):  
MC Moore ◽  
CC Connolly ◽  
AD Cherrington
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Neural Pathways ◽  
Hepatic Glucose Output ◽  
Counterregulatory Hormones ◽  
Hepatic Glucose ◽  
Glucose Output

In vitro evidence indicates that the liver responds directly to changes in circulating glucose concentrations with reciprocal changes in glucose production and that this autoregulation plays a role in maintenance of normoglycemia. Under in vivo conditions it is difficult to separate the effects of glucose on neural regulation mediated by the central nervous system from its direct effect on the liver. Nevertheless, it is clear that nonhormonal mechanisms can cause significant changes in net hepatic glucose balance. In response to hyperglycemia, net hepatic glucose output can be decreased by as much as 60-90% by nonhormonal mechanisms. Under conditions in which hepatic glycogen stores are high (i.e. the overnight-fasted state), a decrease in the glycogenolytic rate and an increase in the rate of glucose cycling within the liver appear to be the explanation for the decrease in hepatic glucose output seen in response to hyperglycemia. During more prolonged fasting, when glycogen levels are reduced, a decrease in gluconeogenesis may occur as a part of the nonhormonal response to hyperglycemia. A substantial role for hepatic autoregulation in the response to insulin-induced hypoglycemia is most clearly evident in severe hypoglycemia (< or = 2.8 mmol/l). The nonhormonal response to hypoglycemia apparently involves enhancement of both gluconeogenesis and glycogenolysis and is capable of supplying enough glucose to meet at least half of the requirement of the brain. The nonhormonal response can include neural signaling, as well as autoregulation. However, even in the absence of the ability to secrete counterregulatory hormones (glucocorticoids, catecholamines, and glucagon), dogs with denervated livers (to interrupt neural pathways between the liver and brain) were able to respond to hypoglycemia with increases in net hepatic glucose output. Thus, even though the endocrine system provides the primary response to changes in glycemia, autoregulation plays an important adjunctive role.

Preserved direct hepatic insulin action in rats with diet-induced hepatic steatosis

2004 ◽  
Vol 286 (5) ◽  
pp. E828-E833 ◽  
Author(s):  
Roland Buettner ◽  
Iris Ottinger ◽  
Jürgen Schölmerich ◽  
L. Cornelius Bollheimer
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Hepatic Glucose Output ◽  
Hepatic Insulin Sensitivity ◽  
Significant Difference ◽  
Hepatic Glucose ◽  
Glucose Output

Recent in vivo studies have demonstrated a strong negative correlation between liver triglyceride content and hepatic insulin sensitivity, but a causal relationship remains to be established. We therefore have examined parameters of direct hepatic insulin action on isolated steatotic livers from high-fat (HF)-fed rats compared with standard chow (SC)-fed controls. Direct hepatic action of insulin was assayed in Wistar rats after 6 wk of HF diet by measuring the insulin-induced suppression of epinephrine-induced hepatic glucose output in an isolated liver perfusion system. Insulin-induced activation of glycogen synthase was measured by quantifying the incorporation of radioactive UDP-glucose into glycogen in HF and SC liver lysates. HF diet induced visceral obesity, mild insulin resistance, and hepatic steatosis. Both suppression of epinephrine-induced glycogenolysis and activation of glycogen synthase by insulin were sustained in HF rats; no significant difference from SC controls could be detected. In conclusion , in our model, triglyceride accumulation into the liver was not sufficient to impair direct hepatic insulin action. The data argue for an important role of systemic factors in the regulation of hepatic glucose output and hepatic insulin sensitivity in vivo.

scholarly journals Restoration of energy homeostasis by SIRT6 extends healthy lifespan

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. Roichman ◽  
S. Elhanati ◽  
M. A. Aon ◽  
I. Abramovich ◽  
A. Di Francesco ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Healthy Aging ◽  
Energy Homeostasis ◽  
De Novo ◽  
Wild Type ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Age Dependent ◽  
Glucose Output

AbstractAging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.

Glucagon-cortisol interactions on glucose turnover and lactate gluconeogenesis in normal humans

1990 ◽  
Vol 258 (4) ◽  
pp. E569-E575 ◽  
Author(s):  
L. Lecavalier ◽  
G. Bolli ◽  
J. Gerich
Keyword(s):  
Glucose Utilization ◽  
Glucose Turnover ◽  
Hepatic Glucose Output ◽  
Experimental Conditions ◽  
Peripheral Tissues ◽  
Persistent Effect ◽  
Lactate Turnover ◽  
Hepatic Glucose ◽  
Normal Humans ◽  
Glucose Output

To determine the mechanism for cortisol enhancement of glucagon-stimulated overall hepatic glucose output (OHGO), we employed the glucose-insulin clamp technique with infusions of [6-3H]glucose and [U-14C]lactate and measured OHGO, glucose utilization, and the turnover and incorporation of lactate in plasma glucose in normal volunteers under four experimental conditions: 1) normoglucagonemia (approximately 150 pg/ml)- normocortisolemia (approximately 14 micrograms/dl); 2) isolated hyperglucagonemia (approximately 550 pg/ml); 3) isolated hypercortisolemia (approximately 32 micrograms/dl); and 4) combined hyperglucagonemia-hypercortisolemia. Isolated hyperglucagonemia caused initial increases in OHGO and lactate gluconeogenesis, which were maximal at 1 h (23.9 +/- 1 and 2.7 +/- 0.4 mumol.kg-1.min-1, respectively) but remained significantly above values in control experiments through 5 h (10.3 +/- 0.7 vs. 8.2 +/- 1.1, P less than 0.03; 2.2 +/- 0.4 vs. 1.2 +/- 0.3, mumol.kg-1.min-1, P less than 0.04, respectively). Hypercortisolemia has no effect on OHGO but increased lactate gluconeogenesis after 3 h. Superimposition of hypercortisolemia on hyperglucagonemia did not further increase OHGO (11.1 +/- 0.7 vs. 10.3 +/- 0.7 mumol.kg-1.min-1, P = NS) but augmented lactate gluconeogenesis additively (isolated hyperglucagonemia = 0.96, isolated hypercortisolemia = 0.98; combined = 2.02 mumol.kg-1.min-1). Neither glucagon nor cortisol affected lactate turnover or glucose utilization. We conclude that glucagon has a persistent effect on OHGO largely accounted for by increased gluconeogenesis. Cortisol augments glucagon-stimulated gluconeogenesis in an additive manner best explained by changes in gluconeogenic enzymes rather than in substrate availability. Finally, the fact that cortisol increased gluconeogenesis without affecting glucose utilization suggests that the liver is more sensitive to the diabetogenic effects of cortisol than are peripheral tissues.

Hepatic glucose production is more sensitive to insulin-mediated inhibition than hepatic VLDL-triglyceride production

2006 ◽  
Vol 291 (6) ◽  
pp. E1360-E1364 ◽  
Author(s):  
Marion A. M. den Boer ◽  
Peter J. Voshol ◽  
Folkert Kuipers ◽  
Johannes A. Romijn ◽  
Louis M. Havekes
Keyword(s):  
Glucose Uptake ◽  
Plasma Insulin ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Hepatic Glucose Output ◽  
Insulin Levels ◽  
Hepatic Glucose ◽  
Plasma Insulin Levels ◽  
Glucose Output ◽  
Vldl Triglyceride

Insulin is an important inhibitor of both hepatic glucose output and hepatic VLDL-triglyceride (VLDL-TG) production. We investigated whether both processes are equally sensitive to insulin-mediated inhibition. To test this, we used euglycemic clamp studies with four increasing plasma concentrations of insulin in wild-type C57Bl/6 mice. By extrapolation, we estimated that half-maximal inhibition of hepatic glucose output and hepatic VLDL-TG production by insulin were obtained at plasma insulin levels of ∼3.6 and ∼6.8 ng/ml, respectively. In the same experiments, we measured that half-maximal decrease of plasma free fatty acid levels and half-maximal stimulation of peripheral glucose uptake were reached at plasma insulin levels of ∼3.0 and ∼6.0 ng/ml, respectively. We conclude that, compared with insulin sensitivity of hepatic glucose output, peripheral glucose uptake and hepatic VLDL-TG production are less sensitive to insulin.

Effect of an insulin infusion on hepatic output of glucose

1960 ◽  
Vol 198 (3) ◽  
pp. 645-648 ◽  
Author(s):  
Melwyn B. Fine ◽  
Robert H. Williams
Keyword(s):  
Portal Vein ◽  
Hepatic Vein ◽  
Insulin Infusion ◽  
Acute Effects ◽  
Hepatic Glucose Output ◽  
Experimental Conditions ◽  
Marked Rise ◽  
Hepatic Glucose ◽  
Glucose Output

Catheters were placed in the hepatic vein and portal vein of normal dogs and were maintained for varying periods of time. With these animals in an unanesthetized state and recovered from the acute effects of the catheter implantations, small amounts of insulin were slowly infused into the portal vein and the hepatic output of glucose was determined. It was concluded that under the experimental conditions insulin did not significantly depress the hepatic output of glucose but that it did inhibit the hepatic response to hypoglycemia. The hepatic glucose output during the infusion was similar to the control values but there was a marked rise in glucose output following the cessation of the infusion.

Pressor doses of angiotensin II increase hepatic glucose output and decrease insulin sensitivity in rats

1996 ◽  
Vol 148 (2) ◽  
pp. 311-318 ◽  
Author(s):  
R H Rao
Keyword(s):  
Angiotensin Ii ◽  
Pressor Response ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Anaesthetized Rats ◽  
Glucose Output

Abstract The metabolic effects of angiotensin II (AII) were studied under steady-state conditions of euglycaemic hyperinsulinaemia in anaesthetized rats. Pressor doses of AII (50 and 400 ng/kg per min) had dose-dependent hypertensive and hyperglycaemic effects during glucose clamp studies. Glucose turnover measurements showed that hepatic glucose output (HGO) increased equally at both pressor doses compared with either saline infusion or AII infusion at a dose without a pressor effect (20 ng/kg per min); however, glucose disposal increased significantly only at 50 ng/kg per min. Infusion of the AII receptor antagonist, saralasin, did not itself alter glucose output or disposal significantly, but it abolished the effects of a simultaneous infusion of All. It is concluded that pressor doses of AII increase HGO by a receptor-mediated mechanism that is not related to the pressor response to the hormone. The hyperglycaemic reaction to this metabolic effect of AII is partially offset by increased glucose disposal at lower doses. The physiological significance of these metabolic actions of AII remains to be established, but they raise the possibility that AII could potentially play a role in glucose homeostasis in vivo. Journal of Endocrinology (1996) 148, 311–318

Glucagon and regulation of glucose metabolism

2003 ◽  
Vol 284 (4) ◽  
pp. E671-E678 ◽  
Author(s):  
Guoqiang Jiang ◽  
Bei B. Zhang
Keyword(s):  
Healthy Subjects ◽  
Critical Role ◽  
Diabetic Patients ◽  
Hepatic Glucose Output ◽  
Glucagon Receptor ◽  
Increase Blood Glucose ◽  
Hepatic Glucose ◽  
Treatment Of Diabetes ◽  
Glucose Output

As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Compared with healthy subjects, diabetic patients and animals have abnormal secretion of not only insulin but also glucagon. Hyperglucagonemia and altered insulin-to-glucagon ratios play important roles in initiating and maintaining pathological hyperglycemic states. Not surprisingly, glucagon and glucagon receptor have been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.

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