Influence of nephrectomy on the glucoregulatory response to insulin administration in the rat

1980 ◽  
Vol 58 (3) ◽  
pp. 301-305 ◽  
Author(s):  
Gavino Perez ◽  
Giacomo Carteni ◽  
Biagio Ungaro ◽  
Luigi Saccà
Keyword(s):  
Plasma Concentrations ◽  
Insulin Injection ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
The Face ◽  
Plasma Insulin Levels ◽  
Glucagon And Insulin ◽  
Glucose Output

Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon and insulin, it was possible to assess the tissue sensitivity to physiologic and supraphysiologic levels of these two hormones and the site of insulin resistance. The effect of an intravenous injection of insulin (100 mU) on glucose turnover was studied in acutely uremic rats 15 h after bilateral nephrectomy and in sham-operated controls, in the postabsorptive state. Glucose output by the liver and uptake by tissues were determined by the primed constant infusion technique using [3-3H]glucose. Under basal conditions, no significant differences in Ra and Rd between the two groups were observed, while a significant hyperglycemia and a reduced glucose metabolic clearance rate in the face of hyperglucagonemia and normal plasma insulin levels were observed in nephrectomized rats. After insulin injection, the glycemic curves were similar in the two groups, while Ra, Rd, and MCR displayed significantly lower values in nephrectomized rats in the face of higher plasma concentrations of insulin and glucagon. It was concluded that acute uremia in the rat is characterized by a loss of the normal ability of insulin to promote peripheral glucose uptake with retention of hepatic sensitivity to insulin.

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.

Glucose and lactate kinetics after endotoxin administration in dogs.

1977 ◽  
Vol 232 (2) ◽  
pp. E180 ◽  
Author(s):  
R R Wolfe ◽  
D Elahi ◽  
J J Spitzer
Keyword(s):  
Lactate Concentration ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Plasma Lactate ◽  
Metabolic Clearance Rate ◽  
Metabolic Substrate ◽  
E Coli ◽  
Lactate Kinetics ◽  
Plasma Lactate Concentration

We studied the effects of E. coli endotoxin on the glucose and lactate kinetics in dogs by means of the primed constant infusion of [6(-3)H] glucose and Na-L-(+)-[U-14C] lactate. The infusion of endotoxin induced a transient hyperglycemic level, followed by a steady fall in plasma glucose to hypoglycemic levels. The rate of appearance (Ra) and the rate of disappearance (Rd) of glucose were both significantly elevated (P less than .05) for 150 min after endotoxin, after which neither differed from the preinfusion value. The metabolic clearance rate of glucose was significantly elevated at all times 30 min postendotoxin. By 30 min postendotoxin, Ra and Rd of lactate, plasma lactate concentration, and the percent of glucose turnover originating from lactate were significantly elevated and remained so for the duration of the experiment. We concluded that after endotoxin hypoglycemia developed because of an enhanced peripheral uptake of glucose and a failure of the liver to maintain an increased Ra of glucose. We also concluded that lactate became an important precursor for gluconeogenesis and an important metabolic substrate.

Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs

1984 ◽  
Vol 246 (1) ◽  
pp. E14-E20
Author(s):  
P. Vaitkus ◽  
A. Sirek ◽  
K. H. Norwich ◽  
O. V. Sirek ◽  
R. H. Unger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Venous Blood ◽  
Compartment Model ◽  
Glucose Turnover ◽  
Base Line ◽  
Indwelling Catheter ◽  
Two Compartment Model ◽  
Portal Venous Blood ◽  
Glucose Output

In response to a single intravenous injection of bovine growth hormone (GH, 100 micrograms/kg) the non-steady-state turnover of glucose, as well as portal levels of insulin (IRI), glucagon (IRG), somatostatin (SRIF), and glucose were determined in normal conscious dogs. Using the two-compartment model validated to calculate rapid turnover changes and tracer infusion methods, the rate of hepatic output of glucose [Ra(t)] was found to be increased, reaching a maximum of 224 mg/min, 7.4 times the basal rate, 4 min after injection of GH. Ra(t) returned to its basal level 35 min later in a damped oscillatory manner. Hormone determinations were carried out in portal venous blood drawn every 2 min for 2 h from an indwelling catheter. IRG peaked 2 min after GH injection and levels of IRI, SRIF, and glucose peaked between 4 and 8 min. Hormone concentrations returned to normal, i.e., were oscillating around base-line levels, about 30 min after GH. These experiments demonstrate for the first time in vivo that a pulse of GH causes transient changes of glucose turnover and measurable alterations of the hormonal homeostasis in the splanchnic area.

In vivo insulin sensitivity in the rat determined by euglycemic clamp

1983 ◽  
Vol 245 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
E. W. Kraegen ◽  
D. E. James ◽  
S. P. Bennett ◽  
D. J. Chisholm
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Porcine Insulin ◽  
Metabolic Clearance ◽  
Conscious Rat ◽  
Insulin Levels ◽  
In Vivo Measurement ◽  
Plasma Insulin Levels

Our aim was to develop the glucose clamp (GC) technique in the conscious rat for assessment of in vivo insulin sensitivity. A 2-h euglycemic GC could be performed in chronically cannulated rats using 625 microliter blood. Overnight-fasted rats were infused with porcine insulin (1.67 mU . kg-1 . h-1). Insulin levels of 41 +/- 2 (SE) mU/liter were produced in rats aged 91 +/- 4 days with a 60- to 120-min glucose infusion rate (GIR60-120) of 10.6 +/- 0.6 mg . kg-1 . min-1 (n = 9) during euglycemia. GIR60-120 was significantly (P less than 0.025) reduced in rats aged greater than 130 days (mean, 169 +/- 16 days) to 7.7 +/- 1.2 mg . kg-1 . min-1 (n = 7). Metabolic clearance rate of porcine insulin (46 +/- 3 ml . kg-1 . min-1) and GIR60-120 compared with plateau plasma insulin levels are higher than values reported in humans. The latter may be due to suppression of a higher basal hepatic glucose production or increased potency of porcine compared with native insulin. We conclude that the GC can be accomplished in the rat. When combined with tracer administration and subsequent killing, it should provide a quantitative in vivo measurement of insulin sensitivity in individual tissues.

Sepsis-induced changes in in vivo insulin action in diabetic rats

1989 ◽  
Vol 257 (3) ◽  
pp. E301-E308 ◽  
Author(s):  
C. H. Lang ◽  
C. Dobrescu
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Hepatic Insulin Resistance ◽  
Blood Levels ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Glucose Output

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.

Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion

2006 ◽  
Vol 291 (5) ◽  
pp. E1131-E1140 ◽  
Author(s):  
Michael Christopher ◽  
Christian Rantzau ◽  
Zhi-Ping Chen ◽  
Rodney Snow ◽  
Bruce Kemp ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Low Dose ◽  
Whole Body ◽  
Glucose Turnover ◽  
Acid Oxidation ◽  
Metabolic Clearance ◽  
The Impact

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-β-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FAOX) blockade by methylpalmoxirate (MP; 5 × 12 hourly 10 mg/kg doses). During the basal equilibrium period (0–150 min), fasting dogs ( n = 8) were infused with [3-3H]glucose followed by either 2-h saline or AICAR (1.5–2.0 mg·kg−1·min−1) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FAOX blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (Rd tissue), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCRg) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC∼pSer221) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and Rd tissue responses were markedly attenuated, but MCRg and GF increased significantly. SkM substrates were unchanged, but ACC∼pSer221 rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FAox blockade.

THE PANCREATIC ALPHA AND BETA CELLS RESPONSES TO 1-ARGININE AND INSULIN-INDUCED HYPOGLYCAEMIA IN HYPERTHYROIDISM

1976 ◽  
Vol 83 (1) ◽  
pp. 114-122 ◽  
Author(s):  
K. Shima ◽  
N. Sawazaki ◽  
R. Tanaka ◽  
S. Morishila ◽  
S. Tarui ◽  
...  
Keyword(s):  
Beta Cells ◽  
Normal Subjects ◽  
Insulin Injection ◽  
Plasma Glucagon ◽  
Arginine Infusion ◽  
Significant Difference ◽  
Functional Defect ◽  
Plasma Insulin Levels ◽  
Glucagon And Insulin ◽  
Insulin Responses

ABSTRACT In order to assess the secretory capacity of the pancreatic alpha and beta cells in patients with hyperthyroidism, the plasma glucagon and insulin responses to 1-arginine and insulin-induced hypoglycaemia in 12 patients were compared with those in 6 normal subjects. The response of beta cell to hypoglycaemia was evaluated by measuring the decrease in plasma C-peptide immunoreactivity (CPR) level. There was a negligible rise in blood glucose and plasma insulin levels in the patients, whereas a significant increase occurred in normal subjects during the arginine infusion. Although no difference in the fasting plasma glucagon concentration between the two groups was found, 30 min after the beginning of the arginine infusion, the plasma glucagon levels rose to a peak of 252 ± 35 pg/ml in the patients, a value significantly lower than 387 ± 53 pg/ml in the normal subjects. The insulin-induced hypoglycaemia caused no significant difference in the peak values of plasma glucagon between the two groups. There was a significant fall in plasma CPR after the insulin injection in both groups but the per cent decrement was rather greater in the patients than in the normal subjects. These results suggest that the pancreatic alpha and beta cells in hyperthyroidism have a functional defect in response to 1-arginine but not to insulin-induced hypoglycaemia. The mechanism involved in these disorders is discussed.

The effect of cold adaptation on kinetics of insulin and growth hormone in heifers

1993 ◽  
Vol 73 (1) ◽  
pp. 33-47 ◽  
Author(s):  
S. L. Scott ◽  
R. J. Christopherson
Keyword(s):  
Growth Hormone ◽  
Cold Adaptation ◽  
Slow Component ◽  
Plasma Concentrations ◽  
Endocrine System ◽  
Insulin Injection ◽  
Metabolic Clearance ◽  
Cold Environment ◽  
Cold Adapted ◽  
Total Turnover

Ten Holstein heifers 1 yr of age were housed in groups of five in temperature-controlled environmental chambers maintained at either 20 °C (warm environment) or − 17 °C (cold environment). Each heifer received an injection of insulin or growth hormone followed by frequent blood sampling. Plasma samples were analyzed for insulin, insulin-like growth factor I (IGF-1), growth hormone, glucagon, triiodothyronine, thyroxine and glucose. Basal plasma concentrations of all hormones except growth hormone and IGF-1 were elevated (P < 0.05) in the cold environment. Kinetic parameters for growth hormone and insulin were calculated using a two-pool model. Both the zero-time intercept and the rate constant for the slow component of growth hormone were lower (P < 0.05) in cold-adapted animals. The total turnover rate of growth hormone in both pools also tended to be reduced by cold adaptation (P < 0.07). The reduction in growth-hormone turnover may be related to the reduced average daily gains that were observed in the cold (P < 0.05). Plasma glucose concentration following both the insulin and growth-hormone injections was higher in the cold-adapted heifers (P < 0.001 and P < 0.05, respectively). The response of glucagon to insulin injection was greater in the cold (P < 0.05), as was the response of IGF-I to growth-hormone injection (P < 0.10). These cold-induced alterations in the endocrine system appear to be directed toward providing substrates, including glucose, for use in thermogenesis rather than growth. Key words: Cold adaptation, growth hormone, insulin, metabolic clearance rate, hormone kinetics, cattle

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.

Effect of human pregnancy on metabolic clearance rate of oxytocin

1990 ◽  
Vol 259 (1) ◽  
pp. R21-R24
Author(s):  
S. Thornton ◽  
J. M. Davison ◽  
P. H. Baylis
Keyword(s):  
Clearance Rate ◽  
Late Pregnancy ◽  
High Plasma ◽  
Constant Infusion ◽  
Aminopeptidase Activity ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Human Pregnancy ◽  
In Pregnancy

The metabolic clearance rate (MCR) of oxytocin (OT) was determined by use of constant infusion techniques to achieve low and high plasma OT concentrations in 10 women in late pregnancy and again 8-10 wk postpartum (mean plasma oxytocinase activity was 2.1 IU/ml plasma at term and less than 0.1 IU/ml plasma 8-10 wk postpartum). At the lower plasma OT concentrations (5.0 and 5.2 pg/ml, pregnant and postpartum, respectively) produced by infusion of 17.9 ng/min in pregnancy and 4.3 ng/min postpartum, mean MCR of OT was increased fourfold during pregnancy (5.7 +/- 0.6 and 1.3 +/- 0.1 l/min, pregnant and postpartum, respectively; P less than 0.001). At the higher plasma OT concentrations (8.0 and 8.0 pg/ml, pregnant and postpartum, respectively) produced by infusion of 35.7 ng/min in pregnancy and 8.5 ng/min postpartum, mean MCR of OT was likewise markedly increased during pregnancy compared with postpartum values (7.1 +/- 1.9 and 1.4 +/- 0.1 l/min, respectively; P less than 0.01). The MCR of OT was independent of plasma concentration (between 5 and 8 pg/ml) during pregnancy and in the postpartum period. It is concluded that the MCR of OT is increased markedly during human pregnancy. This may be due to concomitant increases in in vivo cystine aminopeptidase activity or other less specific pregnancy-associated metabolic changes.

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