Glucose turnover and oxidation are increased in the iron-deficient anemic rat

1986 ◽  
Vol 250 (4) ◽  
pp. E414-E421 ◽  
Author(s):  
S. A. Henderson ◽  
P. R. Dallman ◽  
G. A. Brooks

To test the hypothesis that glucose metabolism is altered by iron deficiency, rates of glucose turnover and oxidation were assessed concurrently with the metabolic rate (VO2) in iron-deficient anemic rats and in normal rats at rest. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient control group) for 3-4 wk. After dietary treatment the iron-deficient group was anemic, with hemoglobin levels of 5.8 +/- 0.2 g/dl, compared with 13.8 +/- 0.4 g/dl for controls. To study glucose metabolism, rats received a 90 min primed-continuous infusion of [6-3H]-and [U-14C]glucose via an indwelling jugular catheter. Serial blood samples were removed from a carotid catheter for determination of glucose concentration and specific activity. Expired air was monitored for VO2, VCO2, and 14CO2. The VO2 (ml X kg-1 X min-1) of iron-deficient rats was 20% higher than controls. Iron-deficient rats had a greater rate of glucose turnover (94 +/- 4 vs. 52 +/- 3 mumol X kg-1 X min-1) and a greater glucose recycling rate, even when normalized to VO2. Despite a higher blood glucose concentration (5.5 +/- 0.6 vs. 4.1 +/- 0.1 mM), the metabolic clearance rate was greater in iron-deficient animals (18 +/- 1 vs. 13 +/- 1 ml X kg-1 X min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

1987 ◽  
Vol 253 (4) ◽  
pp. E461-E466 ◽  
Author(s):  
G. A. Brooks ◽  
S. A. Henderson ◽  
P. R. Dallman

Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 +/- 0.2 compared with 13.8 +/- 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6-3H]glucose and sodium L-[U-14C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly (P less than 0.05) higher blood glucose (7.1 +/- 0.3 vs. 6.1 +/- 0.2 mM) and lactate concentrations than controls (1.0 +/- 0.1 vs. 0.8 +/- 0.1 mM). The iron-deficient group had a significantly higher glucose turnover rate (67 +/- 2 vs. 58 +/- 4 mumol . kg-1 . min-1) than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14C (from infused [14C]-lactate) into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover (irreversible disposal) rates between deficient rats and controls (191 +/- 26 vs. 163 +/- 15 mumol . kg-1 . min-1) was attributed to 14C recycling.(ABSTRACT TRUNCATED AT 250 WORDS)


1976 ◽  
Vol 68 (2) ◽  
pp. 257-264 ◽  
Author(s):  
I. R. McDONALD ◽  
KHIN AYE THAN

SUMMARY Brush-tailed opossums were prepared surgically with indwelling hepatic and jugular venous catheters for blood sampling without disturbance in the conscious state. Hepatic extraction of [125I]Rose Bengal was 21 ± 3 (s.d.)% and hepatic clearance, used as a measure of hepatic blood flow, was 42·5 ± 7 ml/kg/min. Hepatic release of new glucose, calculated from the thoracic vena caval-hepatic venous difference in glucose specific activity at equilibrium during i.v. infusion of [14C]glucose and hepatic blood flow, was 3·5 ± 0·8 mg/ kg/min. This was not changed by i.v. infusion of 10% ethanolic saline or cortisol in ethanolic saline, at 1 mg/kg/h for 90 min, although the cortisol infusion caused the peripheral blood glucose concentration to rise from 56·5 ± 7·3 to 83·2 ± 10·3 mg/100 ml. The rate of metabolic clearance of glucose fell from 6·1 ± 1·1 to 4·2 ± 0·9 ml/kg/min during i.v. cortisol infusion. Daily i.m. injection of 1 mg cortisol acetate/kg for 5 days caused an increase in hepatic new glucose release to 8·0 ± 1·6 mg/kg/min. The findings support the proposition that, in this marsupial, the short-term effect of cortisol on plasma glucose concentration is due to inhibition of peripheral glucose utilization, whereas the long-term effect is due to increased hepatic glucose production.


2021 ◽  
Vol 25 (2) ◽  
pp. 24-32
Author(s):  
Trinh Thach Thi Nguyen ◽  
Duy Tuan Nguyen ◽  
Thanh Ha Tuan Nguyen ◽  
Thi Huong Lan Do ◽  
Hoang Ngan Nguyen

Objective: Evaluation the hypoglycemic effect of Gydenphy capsules on Streptozotocin-induced type 1 diabetic in Swiss mouse model. Methods: The type 1 diabetic model was established by intraperitoneal injections of Streptozocin 150mg/kg in Swiss mouse. Then, the Gydenphy were orally administered daily at a dose of 576 mg/kg/day or 1152 mg/kg/day in 10 days. Blood glucose concentration in the Gydenphy oral groups with that of water control group and the intraperitoneal insulin injection group was compared. Results: Blood glucose concentration in the groups using Gydenphy (dose576 mg/kg/24h and dose 1152 mg/kg/24h) significal decreased compared to the distilled water group at (p <0.05 at the time of 4 hours, 8 hours; p <0.01 at the time of 3, 10 days). The hypoglycemic effect of Gydenphy at 576mg/kg/day and 1152 mg/kg/day at 4 hours, 8 hours and 3 days were inferior to insulin 0.1 UI/kg/day for glycemic control. However, the hypoglycemic effect ofGydenphy were equivalent to insulin after 10 consecutive days on treatment. Conclusion: Gydenphy capsules have hypoglycemic effects onStreptozotocin-induced type 1 diabetes in Swiss mouse model.


2020 ◽  
Author(s):  
Miklós Molnár ◽  
Katalin Horváth ◽  
Tamás Dankó ◽  
Ildikó Somlyai ◽  
Bea Zs Kovács ◽  
...  

Abstract BackgroundDeuterium (D) is a stable isotope of hydrogen (H) with a mass number of 2. It is present in natural waters in the form of HDO, at a concentration of 16.8 mmol/L, equivalent to 150 ppm. In a phase II clinical study, deuterium depletion reduced the fasting glucose concentration and insulin resistance.MethodsIn the study, we tested the effect of subnormal D-concentration on glucose metabolism in streptozotocin (STZ)-induced diabetic rat model. Animals were randomly distributed into 9 groups to test the effect of D2O (in a range of 25-150 ppm) on glucose metabolism in diabetic animals with or without 2X1 unit/day insulin treatment. Serum glucose, -fructose amine-, -HbAIC, –insulin, and urine glucose were tested. After the 8-week treatment, membrane associated GLUT-4 from soleus muscle content was estimated by Western blot technique.ResultsOur results indicate, that deuterium depletion in the presence of insulin reduced the serum glucose, -fructose amine, and -HbAIC, level on dose dependent manner. The optimal concentration of deuterium was between 125-140 ppm. After 8-week period of deuterium depletion the highest membrane-associated GLUT-4 content was detected at 125 ppm.ConclusionsThese data suggest that deuterium depletion dose-dependently enhances insulin’s effect on GLUT-4 translocation and potentiates glucose uptake in diabetic rats, which explains the lower serum glucose, -fructose amine, and -HbAIC concentrations. Based on our experimental data, deuterium-depleted water could be used to treat patients with metabolic syndrome (MS) by increasing the insulin sensitivity. The experiment indicates that the naturally occurring deuterium has an impact on metabolic regulation.


2006 ◽  
Vol 291 (5) ◽  
pp. E1131-E1140 ◽  
Author(s):  
Michael Christopher ◽  
Christian Rantzau ◽  
Zhi-Ping Chen ◽  
Rodney Snow ◽  
Bruce Kemp ◽  
...  

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.


1996 ◽  
Vol 75 (4) ◽  
pp. 593-605 ◽  
Author(s):  
Hilary J. West

There is a paucity of information on the metabolic effects of undernutrition of the ewe carrying multiple fetuses in late pregnancy. In the present study the effects of induction of ketosis from 132 d gestation in ewes carrying twin fetuses were compared with a control group. The ewes were well fed up to 132 d. Ketotic ewes showed a loss of condition score from 3·7 (SE 0·11) at 130 d gestation to 3·0 (SE 0·15) 10 d later after clinical recovery, compared with control twin-pregnant ewes (P < 0·01). The weight loss during the same time period was from 70·6 (SE 2·7) kg at 130 d to 64·2 (SE 2·7) kg at 140 d gestation. As expected, both groups lost weight and condition score in the first 28 d of lactation. Induction of ketosis caused a significant shortening of the gestation period to 142·8 (SE 0·7) d compared with 150 (SE 0·4) d in normal twin-pregnant ewes (P < 0·001). Ewes with induced ketosis recovered clinically and showed a normal feed intake by 3·4 (SE 0·07) d; three required treatment. Induction of ketosis resulted in reduction of hepatic uptake of bromosulphthalein (P < 0·01) and its biliary excretion (P < 0·05), metabolic clearance rate (P < 0·001), fractional clearance (P < 0·001) and 15 and 30 min retention compared with control twin-pregnant ewes. Most values had returned to normal by the first week of lactation. It is thought that in human pregnancy similar changes in bromosulphthalein clearance may be related to reduced binding sites for bromosulphthalein in the liver caused by increased circulating oestrogens. Induction of ketosis resulted in a significant hypoglycaemic (P < 0·01), ketotic (P < 0·001) state compared with well-fed twin-pregnant ewes. These changes could be correlated with the severity of the clinical signs, together with a significant rise in plasma urea (P < 0·001) and NH3 (P < 0·05) concentrations. Again, the return of most of these values to normal by the first week of lactation lends support to the reversibility of hepatic lesions caused by fatty infiltration of the liver. The seventy of this condition in naturally occurring cases suggests that factors other than undernutrition may be contributory, such as the general body condition of the ewe and glucose metabolism by the liver, including the conversion of propionate to glucose.


1995 ◽  
Vol 82 (5) ◽  
pp. 1154-1159 ◽  
Author(s):  
Dounia Sbai ◽  
Philippe Jouvet ◽  
Anne Soulier ◽  
Luc Penicaud ◽  
Jacques Merckx ◽  
...  

Background It should be possible to avoid variations in plasma glucose concentration during anesthesia by adjusting glucose infusion rate to whole-body glucose uptake. To study this hypothesis, we measured glucose utilization and production, before and during halothane anesthesia. Methods After an overnight fast, six adolescents between 12 and 17 yr of age were infused with tracer doses of [6,6-2H2]glucose for 2 h before undergoing anesthesia, and the infusion was continued after induction, until the beginning of surgery. Plasma glucose concentration was monitored throughout, and free fatty acids, lactate, insulin, and glucagon concentrations were measured before and during anesthesia. Results Despite the use of a glucose-free maintenance solution, plasma glucose concentration increased slightly but significantly 5 min after induction (5.3 +/- 0.4 vs. 4.5 +/- 0.4 mmol.l-1, P &lt; 0.05). This early increase corresponded to a significant increase in endogenous glucose production over basal conditions (4.1 +/- 0.4 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P &lt; 0.05), with no concomitant change in peripheral glucose utilization. Fifteen minutes after induction, both glucose utilization and production rates decreased steadily and were 20% less than basal values by 35 min after induction (2.9 +/- 0.3 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P &lt; 0.05). Similarly, glucose metabolic clearance rate decreased by 25% after 35 min. Despite the increase in blood glucose concentration, anesthesia resulted in a significant decrease in plasma insulin concentration. Conclusions These data suggest that halothane anesthesia per se affects glucose metabolism. The decrease in peripheral glucose utilization and metabolic clearance rates and the blunted insulin release question the relevance of glucose infusion in these clinical settings.


1990 ◽  
Vol 258 (6) ◽  
pp. E1037-E1040 ◽  
Author(s):  
C. Cobelli ◽  
G. Toffolo

In vivo studies on the glucose system often require its perturbation by an exogenous input of glucose, whereas glucose turnover is assessed by infusing a glucose tracer. The constant infusion represents the usual format of tracer administration, but it has no clear advantage other than simplicity. Here we propose a different tracer infusion format. It consists of infusing the tracer in parallel with unlabeled glucose so as to maintain a constant specific activity in the infusate. This protocol does not increase experimental complexity and provides new information on the glucose system in non-steady state by allowing reconstruction of the endogenous component of glucose concentration. This reconstruction only requires very general assumptions, such as tracer-tracee indistinguishability and mass conservation; in particular it is independent of the glucose model structure, i.e., number of compartments and their interconnections. A proof of the result is given for a general nonlinear model of the glucose system. The constant specific activity input is also advantageous for non-steady-state calculations, because it reduces the variation in the measured plasma glucose specific activity. The glucose system has served as the prototype, but the protocol is applicable to other blood-borne substances. The radioactive tracer case has been considered, but the same results apply to stable isotope tracers as well; in this case they also become relevant in a somewhat different context, i.e., kinetic studies in steady state.


Author(s):  
Baker F. Mubideen ◽  
Ala-Aldeen Ahmad Al-Serhan ◽  
Justin Z. Amarin ◽  
Arwa Al-Dweikat ◽  
Ra'ad Z. Al-Muhaisen ◽  
...  

Background: Practitioners of traditional medicine use the decoction of Ononis natrix L. to treat hyperglycemia. The literature offers no evidence to support the use. Objective: To investigate the effect of the decoction of Ononis natrix L. on the blood glucose concentration in Wistar rats (Rattus norvegicus) with streptozotocin-induced diabetes mellitus. Methods: We obtained 35 Wistar rats from the animal colony of The University of Jordan School of Medicine. We induced diabetes by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and 23 rats (66%) survived to allocation. We randomly assigned the rats to one of four groups: negative control (1% Tween 80 in distilled water), positive control (100 mg/kg metformin), high-dose treatment (7.5 mL of the decoction), and low-dose treatment (3.5 mL of the decoc-tion). We administered the doses twice daily by oral gavage for two weeks and measured the tail-blood glucose concentration twice daily, once before the first dose and another time after the second dose. We used linear mixed-effects regression to model the change in blood glucose concentration as a function of the experimentation groups, with adjustments for pseu-doreplication and temporal variation. Results: The estimated mean change was 1 mmol/L (−30 to 31 mmol/L) for the negative control group, −26 mmol/L (−56 to 5 mmol/L) for the positive control group, −75 mmol/L (−108 to −42) for the low-dose treatment group, and −82 mmol/L (−111 to −53 mmol/L) for the high-dose treatment group. Conclusion: In conclusion, we demonstrate, for the first time, the hypoglycemic effect of Ononis natrix L. in an animal model of diabetes.


1988 ◽  
Vol 254 (2) ◽  
pp. E137-E143 ◽  
Author(s):  
S. Hulman ◽  
R. Kliegman ◽  
J. Heng ◽  
E. Crouser

Glucose turnover, clearance and response to insulin were determined in fasted newborn and adult dogs. Fasting levels of glucose and insulin and rates of glucose turnover and clearance were not different between the two groups. Blood glucose correlated with basal glucose turnover in newborn pups but not in adult dogs. Glucose turnover was not related to fasting plasma insulin levels. Glucose clearance was an inverse function of blood glucose levels among newborn but not adult dogs. Glucose clearance and blood glucose levels were not related to insulin concentrations. In response to euglycemic hyperinsulinemia, glucose metabolism increased 4-fold among adults but only 1.7-fold in pups. Hyperglycemic hyperinsulinemia increased glucose metabolism in both groups but to a much greater extent in the pups. Euglycemic hyperinsulinemia increased the metabolic clearance rate of glucose 4.2-fold among adults but only 1.8-fold in newborn dogs. In response to hyperglycemic hyperinsulinemia glucose clearance rates were now similar. Despite euglycemic hyperinsulinemia, the newborn dog had an attenuated response to insulin, demonstrating lower rates of glucose metabolism and glucose clearance. The response to the hyperglycemic stimuli suggests that maximal glucose uptake was not achieved during hyperinsulinemia alone. This response supports the concept of glucose-mediated regulation of glucose disposal in newborn animals.


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