Effect of Catecholamines and Dibutyryl-cyclic-AMP on Glucose Turnover, Plasma Free Fatty Acids, and Insulin in Dogs Treated with Methylprednisolone

1972 ◽  
Vol 50 (10) ◽  
pp. 999-1006 ◽  
Author(s):  
Bela Issekutz Jr. ◽  
Ingrid Borkow
Keyword(s):  
Cyclic Amp ◽  
Treated Group ◽  
Glucose Turnover ◽  
Immunoreactive Insulin ◽  
Metabolic Clearance ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Lactate Levels ◽  
Glucose Output ◽  
Hyperglycemic Effect

The turnover rate of glucose was measured in dogs with indwelling arterial and venous catheters, according to the primed constant rate infusion techniques, using 2-3H-glucose as tracer. The effects of adrenalin (A), noradrenalin (NA), and dibutyryl-cAMP (DBcAMP) infusions were tested on normal dogs and on dogs treated for 3 days with methylprednisolone (MP, 3–3.5 mg/kg day). MP potentiated the hyperglycemic effect of A (0.5 μg/kg min) six- to sevenfold, and the increase of hepatic glucose output (Ra) 11-fold. In addition, the free fatty acid (FFA) increasing and lactacidemic effects of A were significantly potentiated by MP. A prevented the rise of immunoreactive insulin even though plasma glucose reached values of 400–450 mg%. The metabolic clearance rate was significantly decreased by A. NA (0.5 μg/kg min) had no hyperglycemic effect in the controls, but it increased the blood sugar by 120 mg% in the treated group. This was caused by a more than twofold increase in the hepatic glucose output. MP treatment did not alter the NA induced rise of FFA and no effect was seen on plasma lactate levels. NA caused a transient rise of insulin in the controls and a greater and more sustained one in treated dogs. Following MP treatment, DBcAMP (0.1 or 0.2 mg/kg min) also caused a much greater hepatic glucose output and hyperglycemia than what had been obtained on the same animals prior to treatment. DBcAMP increased plasma insulin and decreased FFA. It is concluded that the cyclic-AMP sensitivity of hepatic enzyme systems involved in glucose output was greatly increased by MP treatment.

Effects of oxytocin upon the endocrine pancreas secretion and glucose turnover in normal man

1990 ◽  
Vol 123 (5) ◽  
pp. 504-510 ◽  
Author(s):  
Giuseppe Paolisso ◽  
Gennaro Pizza ◽  
Stefano De Riu ◽  
Giuseppe Marrazzo ◽  
Saverio Sgambato ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Infusion ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Hepatic Glucose Output ◽  
Glucose Levels ◽  
Glucose Disappearance ◽  
Hepatic Glucose ◽  
Normal Man ◽  
Glucose Output

Abstract. In normal man oxytocin infusion under basal conditions and at pharmacological doses evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin levels. Simultaneous [D-3H]glucose infusion indicated that oxytocin also produced a prompt and significant increase in hepatic glucose output with a secondary increase in glucose disappearance rate. Eight healthy volunteers were studied during euglycemic glucose clamp and simultaneous [D-3H]glucose infusion, during suppression of endogenous pancreatic secretion by cyclic somatostatin (250 μg/h) and during exogenous glucagon (67 ng/min) and insulin (0.15 mU · kg−1 · min−1 from 0 to 120 min and 0.40 mU · kg−1 · min−1 from 121 to 240 min) replacement. During the first 60 min oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels and hepatic glucose output with a simultaneous suppression of the glucose infusion rate. No difference in glucose disappearance and metabolic clearance rates were recorded throughout the clamp irrespective of whether oxytocin was infused or not. So we conclude that oxytocin exerts a hyperglycemic effect through an A-cell stimulation and a glycogenolytic action.

Effect of phentolamine on the insulin, glucagon, and glucose responses to exercise in adrenal-denervated sheep

1985 ◽  
Vol 63 (4) ◽  
pp. 346-349 ◽  
Author(s):  
Ronald P. Brockman
Keyword(s):  
Sympathetic Innervation ◽  
Adrenergic Innervation ◽  
Metabolic Responses ◽  
Metabolic Clearance ◽  
Adrenergic Stimulation ◽  
Hepatic Glucose Output ◽  
Optimal Response ◽  
Hepatic Glucose ◽  
Alpha Blockade ◽  
Glucose Output

Hyperglycemia and increased hepatic glucose output are characteristic responses to exercise in sheep. They appear to be due in part to α-adrenergic stimulation. To delineate the contributions of sympathetic innervation and adrenal catecholamines to the hormonal and metabolic responses to exercise, adrenal-denervated sheep were exercised with and without α-blockade (phentolamine treatment). Alpha blockade exaggerated the hyperinsulinemia during exercise (increment of 61 ± 8 vs. 34 ± 7 μU/mL for the control). This was associated with a reduction in glucose appearance (increments of 63 ± 8 vs. 236 ± 23 μmol/min, respectively). The metabolic clearance rates were not altered by α-blockade. It appears that both the adrenal catecholamines and adrenergic innervation to the pancreas contribute to the prevention of a rise in insulin concentrations during exercise in sheep. While this may not be essential for glucose appearance to rise during exercise, it appears necessary for an optimal response.

Selective suppression of hepatic glucose output by human proinsulin in the dog

1987 ◽  
Vol 252 (2) ◽  
pp. E230-E236 ◽  
Author(s):  
M. Lavelle-Jones ◽  
M. H. Scott ◽  
O. Kolterman ◽  
A. H. Rubenstein ◽  
J. M. Olefsky ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Hepatic Glucose Output ◽  
Glucose Clamp Technique ◽  
Hepatic Glucose ◽  
The Mean ◽  
Glucose Output

By using the euglycemic glucose-clamp technique we have observed the effects of comparable low dose proinsulin and insulin infusions on isotopically determined glucose turnover in 20 anesthetized dogs. In each animal somatostatin (SRIF) infusion was used to suppress endogenous pancreatic hormone secretion and basal glucagon was replaced. Peripheral proinsulin (0.083 micrograms X kg-1 X min-1) and insulin (350 microU X kg-1 X min-1) levels 15- to 20-fold higher than insulin on a molar basis, based on previous observations that proinsulin has only 5-10% the biologic potency of insulin. Three groups of infusion studies were performed: SRIF and glucagon (n = 5); SRIF, glucagon, and proinsulin (n = 10); and SRIF, glucagon, and insulin (n = 5). The mean serum proinsulin level of 2.43 +/- 0.36 pmol/ml achieved represented a 17-fold excess compared with the mean serum insulin level of 0.14 +/- 0.03 pmol (20 +/- 4 microU/ml). At these concentrations, both hormones reduced hepatic glucose production rates by approximately 50% to 2.0 +/- 0.2 mg X kg-1 X min-1 and 1.8 +/- 0.5 mg X kg-1 X min-1, respectively. In contrast, proinsulin failed to stimulate peripheral glucose utilization, whereas insulin led to a 2.0 +/- 0.3 mg X kg-1 X min-1 increment (approximately 50% increase) in glucose uptake (P less than 0.05). Thus at low infusion rates proinsulin exerts its effect predominantly by suppressing hepatic glucose production without measurable stimulation of peripheral glucose disposal. In contrast, for a comparable degree of hepatic glucose output suppression, insulin also significantly stimulates glucose disposal.

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 glycerol flux after E. coli endotoxin administration

1984 ◽  
Vol 247 (4) ◽  
pp. R687-R692 ◽  
Author(s):  
O. P. McGuinness ◽  
J. J. Spitzer
Keyword(s):  
Blood Flow ◽  
Clearance Rate ◽  
Arterial Blood Flow ◽  
Metabolic Clearance ◽  
Hepatic Glucose Output ◽  
Metabolic Clearance Rate ◽  
Endotoxin Administration ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Glucose Output

Hepatic glycerol flux was examined in dogs after the administration of Escherichia coli endotoxin (0.4 mg/kg) to determine the contribution of the liver to the previously observed decline in the metabolic clearance rate of glycerol. Hepatic glycerol flux was estimated by determining hepatic arterial and portal venous blood flows with electromagnetic flow probes and by measuring arteriovenous difference of glycerol across the liver. Administration of endotoxin significantly decreased total hepatic blood flow (by approximately 20%) but did not alter hepatic arterial blood flow. Hepatic glycerol clearance decreased by 25–30% after endotoxin administration. Hepatic glycerol extraction also decreased. Under control conditions, 60% of the metabolic clearance rate of glycerol was attributable to the liver, whereas in the postendotoxin state approximately 72% of the glycerol clearance could be accounted for by hepatic clearance. Thus changes in transhepatic glycerol flux are only partially responsible for the previously observed alterations in glycerol clearance after endotoxin administration. Although hepatic glycerol clearance decreased, net hepatic glycerol, as well as lactate and alanine, uptake did not decrease, indicating that gluconeogenic precursor availability to the hepatocytes was not diminished. Hepatic glucose output was elevated after endotoxin administration. Changes in hepatic glucose output and gluconeogenic precursor uptake help explain the endotoxin-induced alternations in the fluxes of these metabolites.

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

Lactate metabolism in resting and exercising dogs

1976 ◽  
Vol 40 (3) ◽  
pp. 312-319 ◽  
Author(s):  
B. Issekutz ◽  
W. A. Shaw ◽  
A. C. Issekutz
Keyword(s):  
Constant Infusion ◽  
Metabolic Clearance ◽  
Turnover Rates ◽  
Lactate Turnover ◽  
Hepatic Glucose ◽  
Lactate Levels ◽  
Glucose Output ◽  
Infusion Technique ◽  
Linear Manner

The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18–19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) “in vivo” the major factor which controls both ROX and gluconeogenesis is the substrate supply.

Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs

1983 ◽  
Vol 244 (2) ◽  
pp. E190-E195 ◽  
Author(s):  
R. W. Stevenson ◽  
J. A. Parsons ◽  
K. G. Alberti
Keyword(s):  
Insulin Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Hepatic Glucose Output ◽  
Normal Range ◽  
Hepatic Glucose ◽  
Diabetic Dogs ◽  
Glucose Output ◽  
Glucose Recycling

The effects of peripheral and portal intravenous infusions of insulin on hepatic glucose production and glucose recycling have been compared in conscious diabetic dogs. Glucose turnover (Ra) was estimated using a priming dose of [3-3H]glucose and [1-14C]-glucose followed by constant intravenous infusion. Glucose recycling was calculated from 3H-Ra - 14C-Ra. In eight normal dogs, mean 3H-Ra was 3.0 mg X kg-1 X min-1 and recycling 19%. When these dogs were made diabetic with alloxan and streptozotocin the 3H-Ra rose to 6.2 mg X kg-1 X min-1 (P less than 0.001) and recycling to 24% (P less than 0.05). Insulin infusion for 2.5 h at 0.006 U X kg-1 X h-1 intraportally decreased 3H-Ra to 4.0 mg X kg-1 X min-1 (P less than 0.01 compared with untreated diabetic), whereas peripheral infusion at this rate had no significant effect. Insulin infusion at 0.05 U X kg-1 X h-1 by the peripheral and portal circulations reduced 3H-Ra to the normal range: 3.1 and 2.8 mg X kg-1 X min-1, respectively. Glucose recycling was also normalized by portal insulin infusion (20%) but was significantly decreased by peripheral infusion (11%, P less than 0.01). Thus the liver responds to lower infusion rates of insulin by the intraportal route, and only this mode of administration normalizes both hepatic glucose output and glucose recycling.

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