Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

1987 ◽  
Vol 252 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
G. Paolisso ◽  
A. J. Scheen ◽  
A. S. Luyckx ◽  
P. J. Lefebvre
Keyword(s):  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Metabolic Effects ◽  
Glucose Turnover ◽  
Continuous Administration ◽  
Hepatic Glucose ◽  
Normal Man

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin (100 micrograms X h-1), basal insulin secretion was replaced by a continuous insulin infusion (0.2 mU X kg-1 X min-1), and glucagon was infused intravenously in two conditions at random: either continuously (125 ng X min-1) or intermittently (812.5 ng X min-1, with a switching on/off length of 2/11 min). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3-3H]glucose infusion allowed us to study glucose turnover. While basal plasma glucagon levels were similar in both conditions (122 +/- 31 vs. 115 +/- 18 pg X ml-1), they plateaued at 189 +/- 38 pg X ml-1 during continuous infusion and varied between 95 and 501 pg X ml-1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, did not prevent the so-called “evanescent” effect of glucagon on blood glucose, and after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucagonemia in normal man fails to increase hepatic glucose production.

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.

In vivo deactivation of proinsulin action on glucose disposal and hepatic glucose production in normal man

Diabetes ◽  
1986 ◽  
Vol 35 (3) ◽  
pp. 311-317 ◽  
Author(s):  
H. S. Glauber ◽  
R. R. Revers ◽  
R. Henry ◽  
L. Schmeiser ◽  
P. Wallace ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Normal Man

In Vivo Deactivation of Proinsulin Action on Glucose Disposal and Hepatic Glucose Production in Normal Man

Diabetes ◽  
1986 ◽  
Vol 35 (3) ◽  
pp. 311-317 ◽  
Author(s):  
H. S. Glauber ◽  
R. R. Revers ◽  
R. Henry ◽  
L. Schmeiser ◽  
P. Wallace ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Normal Man

Regulation of glucose turnover and hormonal responses during electrical cycling in tetraplegic humans

1996 ◽  
Vol 271 (1) ◽  
pp. R191-R199 ◽  
Author(s):  
M. Kjaer ◽  
S. F. Pollack ◽  
T. Mohr ◽  
H. Weiss ◽  
G. W. Gleim ◽  
...  
Keyword(s):  
Heart Rate ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Hormonal Responses ◽  
Hepatic Glucose ◽  
Exercise Period ◽  
Exercise Activity ◽  
Beta Hydroxybutyrate

To examine the importance of blood-borne vs. neural mechanisms for hormonal responses and substrate mobilization during exercise, six spinal cord-injured tetraplegic (C5-T1) males (mean age: 35 yr, range: 24-55 yr) were recruited to perform involuntary, electrically induced cycling [functional electrical stimulation (FES)] to fatigue for 24.6 +/- 2.3 min (mean and SE), and heart rate rose from 67 +/- 7 (rest) to 107 +/- 5 (exercise) beats/min. Voluntary arm cranking in tetraplegics (ARM) and voluntary leg cycling in six matched, long-term immobilized (2-12 mo) males (Vol) served as control experiments. In FES, peripheral glucose uptake increased [12.4 +/- 1.1 (rest) to 19.5 +/- 4.3 (exercise) mumol.min-1.kg-1; P < 0.05], whereas hepatic glucose production did not change from basal values [12.4 +/- 1.4 (rest) vs. 13.0 +/- 3.4 (exercise) mumol.min-1.kg-1]. Accordingly, plasma glucose decreased [from 5.4 +/- 0.3 (rest) to 4.7 +/- 0.3 (exercise) mmol/l; P < 0.05]. Plasma glucose did not change in response to ARM or Vol. Plasma free fatty acids and beta-hydroxybutyrate decreased only in FES experiments (P < 0.05). During FES, increases in growth hormone (GH) and epinephrine and decreases in insulin concentrations were abolished. Although subnormal throughout the exercise period, norepinephrine concentrations increased during FES, and responses of heart rate, adrenocorticotropic hormone, beta-endorphin, renin, lactate, and potassium were marked. In conclusion, during exercise, activity in motor centers and afferent muscle nerves is important for normal responses of GH, catecholamines, insulin, glucose production, and lipolysis. Humoral feedback and spinal or simple autonomic nervous reflex mechanisms are not sufficient. However, such mechanisms are involved in redundant control of heart rate and neuroendocrine activity in exercise.

scholarly journals Hepatic functions of GLP-1 and its based drugs: current disputes and perspectives

2016 ◽  
Vol 311 (3) ◽  
pp. E620-E627 ◽  
Author(s):  
Tianru Jin ◽  
Jianping Weng
Keyword(s):  
Insulin Resistance ◽  
Degradation Products ◽  
Hepatic Glucose Production ◽  
Wnt Signaling Pathway ◽  
Glucose Production ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
Metabolic Functions ◽  
Pathway Activation ◽  
Hepatic Glucose

GLP-1 and its based drugs possess extrapancreatic metabolic functions, including that in the liver. These direct hepatic metabolic functions explain their therapeutic efficiency for subjects with insulin resistance. The direct hepatic functions could be mediated by previously assumed “degradation” products of GLP-1 without involving canonic GLP-1R. Although GLP-1 analogs were created as therapeutic incretins, extrapancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important. Postprandial GLP-1 release contributes to insulin secretion, which represses hepatic glucose production. This indirect effect of GLP-1 is known as the gut-pancreas-liver axis. Great efforts have been made to determine whether GLP-1 and its analogs possess direct metabolic effects on the liver, as the determination of the existence of direct hepatic effects may advance the therapeutic theory and clinical practice on subjects with insulin resistance. Furthermore, recent investigations on the metabolic beneficial effects of previously assumed “degradation” products of GLP-1 in the liver and elsewhere, including GLP-128–36 and GLP-132–36, have drawn intensive attention. Such investigations may further improve the development and the usage of GLP-1-based drugs. Here, we have reviewed the current advancement and the existing controversies on the exploration of direct hepatic functions of GLP-1 and presented our perspectives that the direct hepatic metabolic effects of GLP-1 could be a GLP-1 receptor-independent event involving Wnt signaling pathway activation.

scholarly journals Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver

2020 ◽  
Vol 117 (12) ◽  
pp. 6733-6740 ◽  
Author(s):  
Thiago M. Batista ◽  
Sezin Dagdeviren ◽  
Shannon H. Carroll ◽  
Weikang Cai ◽  
Veronika Y. Melnik ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Glycogen Accumulation ◽  
Hepatic Glucose ◽  
Glucose Output

Insulin action in the liver is critical for glucose homeostasis through regulation of glycogen synthesis and glucose output. Arrestin domain-containing 3 (Arrdc3) is a member of the α-arrestin family previously linked to human obesity. Here, we show thatArrdc3is differentially regulated by insulin in vivo in mice undergoing euglycemic-hyperinsulinemic clamps, being highly up-regulated in liver and down-regulated in muscle and fat. Mice with liver-specific knockout (KO) of the insulin receptor (IR) have a 50% reduction inArrdc3messenger RNA, while, conversely, mice with liver-specific KO ofArrdc3(L-Arrdc3KO) have increased IR protein in plasma membrane. This leads to increased hepatic insulin sensitivity with increased phosphorylation of FOXO1, reduced expression of PEPCK, and increased glucokinase expression resulting in reduced hepatic glucose production and increased hepatic glycogen accumulation. These effects are due to interaction of ARRDC3 with IR resulting in phosphorylation of ARRDC3 on a conserved tyrosine (Y382) in the carboxyl-terminal domain. Thus,Arrdc3is an insulin target gene, and ARRDC3 protein directly interacts with IR to serve as a feedback regulator of insulin action in control of liver metabolism.

scholarly journals P0950EFFECT OF THYROID HORMONE TREATMENT ON RENAL REABSORPTION OF GLUCOSE IN ALLOXAN-INDUCED DIABETIC RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gireesh Dayma
Keyword(s):  
Blood Glucose ◽  
Thyroid Hormone ◽  
Glucose Homeostasis ◽  
Hepatic Glucose Production ◽  
Liver Perfusion ◽  
Glucose Production ◽  
Diabetic Rats ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Renal Expression

Abstract Background and Aims The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Method Adult male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 ?g/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. Results After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Conclusion Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

Effects of norepinephrine infusion on in vivo insulin sensitivity and responsiveness

1990 ◽  
Vol 259 (2) ◽  
pp. E210-E215 ◽  
Author(s):  
J. R. Lupien ◽  
M. F. Hirshman ◽  
E. S. Horton
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Peripheral Tissues

The effect of a continuous infusion of norepinephrine (NE) on glucose disposal in vivo was examined in conscious restrained rats using the euglycemic-hyperinsulinemic clamp technique. NE, 1,000 micrograms.kg-1.day-1 (130 nmol.kg-1.h-1) or vehicle (CO) was infused for 10 days in adult male Sprague-Dawley rats using subcutaneously implanted osmotic minipumps. Body weight and food intake were similar in both groups of animals throughout the study. Fasting basal plasma glucose and insulin concentrations were similar in both groups. However, basal hepatic glucose production (HGP) was increased by NE treatment (9.03 +/- 0.63 vs. 13.20 +/- 1.15 mg.kg-1.min-1, P less than 0.05, CO vs. NE, respectively). Insulin infusions of 2, 6, and 200 mU.kg-1.min-1 suppressed HGP to the same degree in both groups. During 2, 6, and 200 mU.kg-1.h-1 insulin infusions the glucose disposal rate was 65, 60, and 13% greater in NE-treated animals than in controls. Acute beta-adrenergic blockade with propranolol infused at 405 nmol.kg-1.h-1 during the glucose clamps did not normalize glucose disposal. These results demonstrate that chronic NE infusion is associated with increased basal glucose turnover and increased insulin sensitivity of peripheral tissues.

scholarly journals Glucagon Deficiency Reduces Hepatic Glucose Production and Improves Glucose Tolerance In Adult Mice

2010 ◽  
Vol 31 (4) ◽  
pp. 606-606
Author(s):  
Aidan S. Hancock ◽  
Aiping Du ◽  
Jingxuan Liu ◽  
Mayumi Miller ◽  
Catherine L. May
Keyword(s):  
Glucose Homeostasis ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Postprandial Glucose ◽  
Glucagon Receptor ◽  
Glucose Levels ◽  
Adult Mice ◽  
Hepatic Glucose ◽  
Knockout Animals

Abstract The major role of glucagon is to promote hepatic gluconeogenesis and glycogenolysis to raise blood glucose levels during hypoglycemic conditions. Several animal models have been established to examine the in vivo function of glucagon in the liver through attenuation of glucagon via glucagon receptor knockout animals and pharmacological interventions. To investigate the consequences of glucagon loss to hepatic glucose production and glucose homeostasis, we derived mice with a pancreas specific ablation of the α-cell transcription factor, Arx, resulting in a complete loss of the glucagon-producing pancreatic α-cell. Using this model, we found that glucagon is not required for the general health of mice but is essential for total hepatic glucose production. Our data clarifies the importance of glucagon during the regulation of fasting and postprandial glucose homeostasis.

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.

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