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 < 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 < 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.

scholarly journals Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons

2020 ◽  
Vol 6 (23) ◽  
pp. eaaz1341 ◽  
Author(s):  
Sai P. Pydi ◽  
Zhenzhong Cui ◽  
Zhenyan He ◽  
Luiz F. Barella ◽  
Jonathan Pham ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Peripheral Tissues ◽  
Metabolic Phenotypes ◽  
Metabolic Role ◽  
Hepatic Glucose ◽  
Obesogenic Diet ◽  
Metabolic Impairments

β-Arrestin-1 and β-arrestin-2 have emerged as important signaling molecules that modulate glucose fluxes in several peripheral tissues. The potential roles of neuronally expressed β-arrestins in regulating glucose homeostasis remain unknown. We here report that mice lacking β-arrestin-1 (barr1) selectively in AgRP neurons displayed impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet, while mice overexpressing barr1 selectively in AgRP neurons were protected against obesity-associated metabolic impairments. Additional physiological, biochemical, and electrophysiological data indicated that the presence of barr1 is essential for insulin-mediated hyperpolarization of AgRP neurons. As a result, barr1 expressed by AgRP neurons regulates efferent neuronal pathways that suppress hepatic glucose production and promote lipolysis in adipose tissue. Mice lacking β-arrestin-2 (barr2) selectively in AgRP neurons showed no substantial metabolic phenotypes. Our data suggest that agents able to enhance the activity of barr1 in AgRP neurons may prove beneficial as antidiabetic drugs.

The role of autoregulation of the hepatic glucose production in man. Response to a physiologic decrement in plasma glucose

Diabetes ◽  
1986 ◽  
Vol 35 (2) ◽  
pp. 186-191 ◽  
Author(s):  
I. Hansen ◽  
R. Firth ◽  
M. Haymond ◽  
P. Cryer ◽  
R. Rizza
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose

Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity

1993 ◽  
Vol 265 (2) ◽  
pp. E275-E283 ◽  
Author(s):  
M. Kjaer ◽  
K. Engfred ◽  
A. Fernandes ◽  
N. H. Secher ◽  
H. Galbo
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Constant Infusion ◽  
Intense Exercise ◽  
Nerve Activity ◽  
Hepatic Glucose ◽  
Sympathoadrenergic Activity ◽  
Exercise In Humans

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Glucagon enhances the direct suppressive effect of insulin on hepatic glucose production in humans

1997 ◽  
Vol 272 (3) ◽  
pp. E371-E378 ◽  
Author(s):  
G. F. Lewis ◽  
M. Vranic ◽  
A. Giacca
Keyword(s):  
Type I Diabetes ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Insulin Delivery ◽  
Suppressive Effect ◽  
Type I ◽  
Constant Rate ◽  
Hepatic Glucose ◽  
Infusion Method

The present study examines the role of glucagon in modulating the hepatic and extrahepatic effects of insulin on hepatic glucose production (HGP). We infused glucagon at a constant rate (0.65 ng x kg(-1) x min(-1)) during equimolar portal and peripheral insulin delivery in seven healthy males by our previously published tolbutamide infusion method. In contrast to our previous study, in which glucagon fell by approximately 30% during hyperinsulinemia and suppression of HGP was significantly greater with equimolar peripheral than with portal insulin delivery, HGP was actually suppressed to a lesser extent with peripheral insulin delivery (69 +/- 10%) than when insulin was delivered portally (76 +/- 5%, P < 0.05). To further examine whether glucagon was enhancing the effect of portal insulin, in four additional individuals HGP was suppressed to a greater extent during a tolbutamide infusion when glucagon was administered continuously throughout the basal and hyperinsulinemic periods than when glucagon was infused during the basal period only; HGP suppressed by 63 +/- 3 vs. 52 +/- 3%, respectively, P = 0.02). Tolbutamide had no effect on HGP when infused into three C-peptide-negative individuals with type I diabetes during a low-dose insulin and glucagon infusion. These data suggest that glucagon levels are an important determinant of the balance between insulin's direct and indirect effects on HGP, with glucagon likely potentiating the direct hepatic effect of insulin.

Predominant Role of Gluconeogenesis in Increased Hepatic Glucose Production in NIDDM

Diabetes ◽  
1989 ◽  
Vol 38 (5) ◽  
pp. 550-557 ◽  
Author(s):  
A. Consoli ◽  
N. Nurjhan ◽  
F. Capani ◽  
J. Gerich
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Predominant Role ◽  
Hepatic Glucose

THE ROLE OF iNOS FOR HEPATIC GLUCOSE PRODUCTION IN MURINE SEPTIC SHOCK

Shock ◽  
2006 ◽  
Vol 26 (Supplement 1) ◽  
pp. 3-4
Author(s):  
G. Albuszies ◽  
J. Vogt ◽  
P. Radermacher ◽  
S. Weber ◽  
U. Wachter ◽  
...  
Keyword(s):  
Septic Shock ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose

scholarly journals Hepatocyte serine palmitoyl transferase 2 deficiency promotes liver C16:0-ceramide accumulation through sphingomyelin hydrolysis and leads to liver damage and dysfunction in mice

2021 ◽  
Author(s):  
Justine Lallement ◽  
Ilyès Raho ◽  
Gregory Merlen ◽  
Dominique Rainteau ◽  
Mikael Croyal ◽  
...  
Keyword(s):  
Bile Acid ◽  
Glucose Tolerance ◽  
Metabolic Disorders ◽  
De Novo ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Lipid Absorption ◽  
Compensatory Mechanism ◽  
Hepatic Glucose

Objectives: Ceramides have been shown as lipotoxic inducers, which can trigger apoptosis, inflammation and disturb numerous cell signalling pathways leading to metabolic disorders such as type 2 diabetes (T2D). In this study, we aimed to determine the role of de novo hepatic ceramide synthesis on energy and liver homeostasis in mice. Methods: In order to investigate hepatic role of de novo ceramides synthesis, we generated mice lacking serine palmitoyltransferase 2 (Sptlc2) in hepatocytes using the cre-lox system. SPTLC2 allows condensation of serine and palmitoylCoA and is the rate limiting-enzyme necessary for ceramide de novo synthesis. Sptlc2ΔHep and their littermate controls were fed with high fat diet (HFD) to induce metabolic disorders. Liver ceramides content and metabolic parameters as glucose tolerance, insulin sensitivity, and hepatic glucose production were assessed. As ceramides may have impact on bile acids (BA), we investigated BA pool composition, synthesis and transport. Finally, inflammation and apoptosis were measured in the liver using western blot analysis, pro-inflammatory cytokines expression level and immunohistochemistry. Results: Despite lower expression of hepatic Sptlc2, we observed an increased concentration of hepatic ceramides, especially C16:0-ceramide. Hepatic deletion of Sptlc2 in mice was also associated with an increased neutral sphingomyelinase 2 (nSmase2) expression, and a decreased sphingomyelin content in the liver. We showed that Sptlc2ΔHep mice are protected against body mass gain normally induced by HFD and displayed a decreased body fat mass. BA hydrophobicity was drastically decreased in Sptlc2ΔHep mice, and was associated with a defect in lipid absorption. In addition, an important increase of tauro-murocholic acid T-MCA in BA pool composition of Sptlc2ΔHep mice was associated with a downregulation of the nuclear bile acid receptor FXR target genes in ileum and liver. Sptlc2 deficiency also enhanced glucose tolerance and attenuated hepatic glucose production in an insulin-independent manner. Finally, Sptlc2 disruption promoted progressive development of hepatic fibrosis, apoptosis and inflammation in an age-related manner. Conclusion: Our data demonstrate for the first time a potential compensatory mechanism to regulate hepatic ceramides content from sphingomyelin hydrolysis. In addition, our results highlight the role of hepatic sphingolipid modulation on hepatic glucose production through bile acid composition changes.

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.

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