Chronic glucose-lowering effects of rosiglitazone and bis(ethylmaltolato)oxovanadium(IV) in ZDF rats

2003 ◽  
Vol 81 (11) ◽  
pp. 1049-1055 ◽  
Author(s):  
Violet G Yuen ◽  
Sanjay Bhanot ◽  
Mary L Battell ◽  
Chris Orvig ◽  
John H McNeill
Keyword(s):  
Plasma Glucose ◽  
Additive Effect ◽  
Glucose Lowering ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Age Dependent ◽  
Plasma Insulin Levels ◽  
Zdf Rats ◽  
Glucose Lowering Effect ◽  
Food And Fluid Intake

The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1, 6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 µmol/kg) were selected to produce a glucose-lowering effect in 30% (ED30) of animals. Both drugs were administered daily by oral gavage as suspensions in 1% carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume administered to all rats was 5 mL/(kg·day). The combination of BEOV and ROS was effective in lowering plasma glucose levels to <9 mmol/L in 60% of fatty animals as compared with 30% for BEOV and 10% for ROS alone. The age-dependent decrease in plasma insulin levels associated with β-cell failure in the ZDF rats did not occur in the BEOV-treated fatty groups. There was no effect of any treatment on body weight; however, there was a significant reduction in both food and fluid intake in fatty groups treated with BEOV. There were no overt signs of toxicity and no mortality in this study. Both BEOV and ROS were effective in lowering plasma glucose levels, as stated above, and there was at least an additive effect when BEOV and ROS were used in combination.Key words: rosigitazone, bis(ethylmaltolato)oxovanadium(IV), diabetes, ZDF rats.

Insulin modulates glucose-dependent insulinotropic polypeptide (GIP) secretion from enteroendocrine K cells in rats

2011 ◽  
Vol 392 (10) ◽  
pp. 909-918 ◽  
Author(s):  
Nigel Irwin ◽  
Jacqueline M.E. Francis ◽  
Peter R. Flatt
Keyword(s):  
Plasma Glucose ◽  
Oral Glucose ◽  
Glucose Lowering ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Elevated Glucose ◽  
Plasma Insulin Levels ◽  
Glucose Plasma ◽  
And Control ◽  
Intestinal Weight

Abstract Effects of insulin excess and deficiency on glucose-dependent insulinotropic polypeptide (GIP) was examined in rats following insulinoma transplantation or streptozotocin (STZ) administration. Over 14 days, food intake was increased (p<0.001) in both groups of rats, with decreased body weight (p<0.01) in STZ rats. Non-fasting plasma glucose levels were decreased (p<0.01) and plasma insulin levels increased (p<0.001) in insulinoma-bearing rats, whereas STZ treatment elevated glucose (p<0.001) and decreased insulin (p<0.01). Circulating GIP concentrations were elevated (p<0.01) in both animal models. At 14 days, oral glucose resulted in a decreased glycaemic excursion (p<0.05) with concomitant elevations in insulin release (p<0.001) in insulinoma-bearing rats, whereas STZ-treated rats displayed similar glucose-lowering effects but reduced insulin levels (p<0.01). GIP concentrations were augmented in STZ rats (p<0.05) following oral glucose. Plasma glucose and insulin concentrations were not affected by oral fat, but fat-induced GIP secretion was particularly (p<0.05) increased in insulinoma-bearing rats. Exogenous GIP enhanced (p<0.05) glucose-lowering in all groups of rats accompanied by insulin releasing (p<0.001) effects in insulinoma-bearing and control rats. Both rat models exhibited increased (p<0.001) intestinal weight but decreased intestinal GIP concentrations. These data suggest that circulating insulin has direct and indirect effects on the synthesis and secretion of GIP.

Rapid translocation of hepatic glucokinase in response to intraduodenal glucose infusion and changes in plasma glucose and insulin in conscious rats

2004 ◽  
Vol 286 (4) ◽  
pp. G627-G634 ◽  
Author(s):  
Chang An Chu ◽  
Yuka Fujimoto ◽  
Kayano Igawa ◽  
Joseph Grimsby ◽  
Joseph F. Grippo ◽  
...  
Keyword(s):  
Portal Vein ◽  
Plasma Glucose ◽  
Regulatory Protein ◽  
Glucose Infusion ◽  
Insulin Levels ◽  
Conscious Rats ◽  
Glucose Levels ◽  
Glucose Ingestion ◽  
Plasma Insulin Levels

The rate of liver glucokinase (GK) translocation from the nucleus to the cytoplasm in response to intraduodenal glucose infusion and the effect of physiological rises of plasma glucose and/or insulin on GK translocation were examined in 6-h-fasted conscious rats. Intraduodenal glucose infusion (28 mg·kg-1·min-1 after a priming dose at 500 mg/kg) elevated blood glucose levels (mg/dl) in the artery and portal vein from 90 ± 3 and 87 ± 3 to 154 ± 4 and 185 ± 4, respectively, at 10 min. At 120 min, the levels had decreased to 133 ± 6 and 156 ± 5, respectively. Plasma insulin levels (ng/ml) in the artery and the portal vein rose from 0.7 ± 0.1 and 1.8 ± 0.3 to 11.8 ± 1.5 and 20.2 ± 2.0 at 10 min, respectively, and 12.4 ± 3.1 and 18.0 ± 4.8 at 30 min, respectively. GK was rapidly exported from the nucleus as determined by measuring the ratio of the nuclear to the cytoplasmic immunofluorescence (N/C) of GK (2.9 ± 0.3 at 0 min to 1.7 ± 0.2 at 10 min, 1.5 ± 0.1 at 20 min, 1.3 ± 0.1 at 30 min, and 1.3 ± 0.1 at 120 min). When plasma glucose (arterial; mg/dl) and insulin (arterial; ng/ml) levels were clamped for 30 min at 93 ± 7 and 0.7 ± 0.1, 81 ± 5 and 8.9 ± 1.3, 175 ± 5 and 0.7 ± 0.1, or 162 ± 5 and 9.2 ± 1.5, the N/C of GK was 3.0 ± 0.5, 1.8 ± 0.1, 1.5 ± 0.1, and 1.2 ± 0.1, respectively. The N/C of GK regulatory protein (GKRP) did not change in response to the intraduodenal glucose infusion or the rise in plasma glucose and/or insulin levels. The results suggest that GK but not GKRP translocates rapidly in a manner that corresponds with changes in the hepatic glucose balance in response to glucose ingestion in vivo. Additionally, the translocation of GK is induced by the postprandial rise in plasma glucose and insulin.

Swim training alters sympathoadrenal and endocrine responses to hemorrhage in borderline hypertensive rats

1995 ◽  
Vol 269 (1) ◽  
pp. R124-R130
Author(s):  
D. E. McCoy ◽  
J. E. Steele ◽  
R. H. Cox ◽  
R. L. Wiley
Keyword(s):  
Plasma Glucose ◽  
Plasma Insulin ◽  
Rest Period ◽  
Endocrine Function ◽  
Plasma Norepinephrine ◽  
Hypertensive Rats ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Plasma Insulin Levels ◽  
Positive Correlations

Swim training alters cardiovascular, sympathoadrenal, and endocrine responses to hemorrhage in borderline hypertensive rats (BHR). The effects of 10, 20, and 30% blood volume hemorrhages on cardiovascular, sympathoadrenal, and endocrine function in swim-trained (T; 2 h/day, 5 day/wk for 10-12 wk) and age-matched, untrained, sedentary, control (UT) borderline hypertensive rats (BHR) were assessed. Heart rate (HR) in UT BHR was significantly greater during the baseline (rest) period than T BHR. HR increased slightly from baseline in both groups after 10% hemorrhage but was significantly decreased in both groups after 20 and 30% hemorrhages. The decrease was eliminated by atropine (1 mg/kg iv). Systolic (SBP) and diastolic (DBP) blood pressures decreased significantly after 20 and 30% hemorrhages in both T and UT BHR but were not different between the groups at these times. Plasma norepinephrine levels were significantly increased above baseline after 20 and 30% hemorrhages in UT BHR and were significantly greater in UT BHR than T BHR after 30% hemorrhage. Plasma glucose levels increased significantly after 30% hemorrhage in both groups but were significantly greater in UT BHR than T BHR. Both plasma norepinephrine and plasma epinephrine levels showed strong positive correlations with plasma glucose. After 20 and 30% hemorrhages, plasma insulin levels were unchanged in T BHR but were significantly decreased in UT BHR. Plasma insulin levels were significantly less in UT than T BHR after 30% hemorrhage. These results suggest that swim training alters the effect that hemorrhage exerts on endocrine and sympathoadrenal function in BHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of adrenaline on insulin secretion in rats treated chronically with adrenaline

1976 ◽  
Vol 54 (6) ◽  
pp. 870-875 ◽  
Author(s):  
Suzanne Rousseau-Migneron ◽  
André Nadeau ◽  
Jacques LeBlanc
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Basal Insulin ◽  
Plasma Insulin ◽  
Intravenous Glucose ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Plasma Insulin Levels ◽  
Adrenaline Infusion

To determine whether rats could adapt to a chronic exogenous supply of adrenaline by a decrease in the well-known inhibitory effect of adrenaline on insulin secretion, plasma glucose and insulin levels were measured in unanesthetized control and adrenaline-treated rats (300 μg/kg twice a day for 28 days) during an adrenaline infusion (0.75 μg kg−1 min−1), after an acute glucose load (0.5 g/kg), and during the simultaneous administration of both agents. Chronic treatment with adrenaline did not modify the initial glucose levels but it greatly diminished the basal insulin values (21.57 ± 2.48 vs. 44.69 ± 3.3 μU/ml, p < 0.01). In the control rats, despite the elevated glucose concentrations, a significant drop in plasma insulin levels was observed within the first 15 min of adrenaline infusion, followed by a period of recovery. In the adrenaline-treated group, in which plasma glucose levels were lower than in control animals, plasma insulin levels did not drop as in control rats, but a significant increase was found after 30 min of infusion. During the intravenous glucose tolerance test, the plasma glucose and insulin responses showed similar patterns; however, during the concomitant adrenaline infusion, the treated rats showed a better glucose tolerance than their controls. These results indicate that rats chronically treated with adrenaline adapt to the diabetogenic effect of an infusion of adrenaline by having a lower inhibition of insulin release, although the lower basal insulin levels may indicate a greater sensitivity to endogenous insulin.

Pre- and postabsorptive insulin secretion in chronic decerebrate rats

1986 ◽  
Vol 250 (4) ◽  
pp. R539-R548 ◽  
Author(s):  
F. W. Flynn ◽  
K. C. Berridge ◽  
H. J. Grill
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Oral Glucose ◽  
Base Line ◽  
Intravenous Glucose ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Percent Change ◽  
Plasma Insulin Levels

Basal, taste-stimulated (preabsorptive), and postabsorptive insulin secretion and plasma glucose responses were studied in chronic decerebrate rats and their pair-fed neurologically intact controls. In experiment 1, preabsorptive insulin responses (PIR) elicited by oral infusions of glucose solution was measured in chronic decerebrate rats. Oral glucose was ingested and led to a significant short-latency elevation in plasma insulin levels. Plasma glucose levels remained constant during this time. These data show that caudal brain stem mechanisms, in isolation of the forebrain, are sufficient for the neurally mediated PIR elicited by oral glucose stimulation. In experiment 2, effects of decerebration on postabsorptive insulin secretion were measured. During the 3 h immediately after transection there was no effect of decerebration on peripheral plasma insulin or glucose levels. Thereafter, however, basal plasma insulin levels of decerebrate rats were at least twice that of control rats. Plasma glucose levels of both groups remained identical despite the hyperinsulinemia in decerebrate rats. Atropine treatment decreased, and phentolamine administration elicited a greater absolute and percent change increase in insulin levels of decerebrate rats. These data indicate that altered autonomic tone contributes to maintaining the basal hyperinsulinemia in the decerebrate rat. In response to intragastric meals and glucose and intravenous glucose administration, insulin secretion was greater in decerebrate than in control rats. Percent change in insulin levels from base line was similar in both groups after intragastric meals and intravenous glucose. In response to intragastric glucose, however, percent increase in insulin levels was greater in decerebrate rats. Decerebrate rats demonstrated mild glucose intolerance after intragastric and intravenous treatments. These results are contrasted with the known effects of ventromedial hypothalamic lesions on insulin secretion and glucose homeostasis.

Effect of adrenal demedullation and (or) physical training on glucose tolerance in the rat

1993 ◽  
Vol 71 (12) ◽  
pp. 931-937 ◽  
Author(s):  
Christine Jean ◽  
Gilles Tancrède ◽  
André Nadeau
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Physical Training ◽  
Plasma Insulin ◽  
Intravenous Glucose ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Basal Plasma ◽  
Plasma Insulin Levels

Physical training increases insulin sensitivity by mechanisms not yet fully understood. Because exercise also modulates adrenergic system activity, the present study was designed to ascertain whether the improved glucose homeostasis observed in trained rats is influenced by epinephrine secretion from the adrenal medullae. Male Wistar rats previously submitted to adrenal demedullation or sham operated were kept sedentary or trained on a treadmill over a 10-week period. An intravenous glucose tolerance test (IVGTT) was done 64 h after the last bout of exercise. Basal plasma glucose levels were reduced by physical training (p < 0.005) and by adrenal demedullation (p < 0.001). Adrenodemedullated rats had lower (p < 0.005) plasma glucose levels than sham-operated animals over the whole glucose tolerance curve. Trained animals had lower (p < 0.01) plasma glucose levels than sedentary rats throughout the IVGTT, except at 45 min. The glucose disappearance rate measured after the glucose bolus injection was increased by training (p < 0.05), whereas it was not modified by adrenal demedullation. Basal plasma insulin levels were reduced (p < 0.001) by physical training but unaffected by adrenal demedullation. During the IVGTT, adrenodemedullated rats had higher (p < 0.01) plasma insulin levels at 2, 4, and 6 min, whereas trained animals had lower (p < 0.05) plasma insulin levels throughout the test. Moreover, insulin in adrenodemedullated and trained rats had returned to basal levels at 30 min. The area under the curve for insulin was diminished by physical training (p < 0.001) but was not modified by adrenal demedullation. In the basal state and during the IVGTT, the sedentary adrenodemedullated rats had higher (p < 0.05) plasma glucagon levels compared with the other groups of animals. Pancreatic insulin content was not modified by adrenal demedullation but was diminished (p < 0.01) by physical training. The pancreatic glucagon content was not altered by adrenal demedullation or physical training. Because adrenal demedullation abolished the exercise-induced increase in epinephrine secretion, the results of the present study suggest that the enhanced insulin sensitivity induced by physical training is not caused by an increase in epinephrine secretion from the adrenal medullae.Key words: adrenal demedullation, physical training, glucose tolerance, insulin sensitivity, catecholamines.

scholarly journals Intestinal bile acid sequestration improves glucose control by stimulating hepatic miR-182-5p in type 2 diabetes

2018 ◽  
Vol 315 (5) ◽  
pp. G810-G823 ◽  
Author(s):  
Leslie R. Sedgeman ◽  
Carine Beysen ◽  
Ryan M. Allen ◽  
Marisol A. Ramirez Solano ◽  
Scott M. Turner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Glycemic Control ◽  
Mediator Complex ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Zdf Rats ◽  
Direct Target

Colesevelam is a bile acid sequestrant approved to treat both hyperlipidemia and type 2 diabetes, but the mechanism for its glucose-lowering effects is not fully understood. The aim of this study was to investigate the role of hepatic microRNAs (miRNAs) as regulators of metabolic disease and to investigate the link between the cholesterol and glucose-lowering effects of colesevelam. To quantify the impact of colesevelam treatment in rodent models of diabetes, metabolic studies were performed in Zucker diabetic fatty (ZDF) rats and db/db mice. Colesevelam treatments significantly decreased plasma glucose levels and increased glycolysis in the absence of changes to insulin levels in ZDF rats and db/db mice. High-throughput sequencing and real-time PCR were used to quantify hepatic miRNA and mRNA changes, and the cholesterol-sensitive miR-96/182/183 cluster was found to be significantly increased in livers from ZDF rats treated with colesevelam compared with vehicle controls. Inhibition of miR-182 in vivo attenuated colesevelam-mediated improvements to glycemic control in db/db mice. Hepatic expression of mediator complex subunit 1 (MED1), a nuclear receptor coactivator, was significantly decreased with colesevelam treatments in db/db mice, and MED1 was experimentally validated to be a direct target of miR-96/182/183 in humans and mice. In summary, these results support that colesevelam likely improves glycemic control through hepatic miR-182–5p, a mechanism that directly links cholesterol and glucose metabolism. NEW & NOTEWORTHY Colesevelam lowers systemic glucose levels in Zucker diabetic fatty rats and db/db mice and increases hepatic levels of the sterol response element binding protein 2-responsive microRNA cluster miR-96/182/183. Inhibition of miR-182 in vivo reverses the glucose-lowering effects of colesevelam in db/db mice. Mediator complex subunit 1 (MED1) is a novel, direct target of the miR-96/182/183 cluster in mice and humans.

Blood Glucose Lowering Effect by an Extract from Aronia (Aronia melanocarpa) – a pilot intervention study

2021 ◽  
Vol 02 ◽  
Author(s):  
Kirsten Berger ◽  
Johanna Josefine Ostberg-Potthoff ◽  
Tamara Bakuradze ◽  
Peter Winterhalter ◽  
Elke Richling
Keyword(s):  
Blood Glucose ◽  
Intervention Study ◽  
Grape Juice ◽  
Protective Effects ◽  
Glucose Lowering ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Red Grape ◽  
Pilot Intervention ◽  
Phenolic Extracts

Background: The polyphenols from red fruits exhibit protective effects against degenerative diseases, including diabetes mellitus type 2, cardiovascular disease, etc. Objective: In this small pilot intervention study with only ten volunteers, we investigated the influence of phenolic extracts prepared from an Aronia juice and a red grape juice concentrate on peripheral glucose, blood glucose, and insulin after the intake of a drink containing these extracts plus maltodextrin and water. Method: Maltodextrin in water served as control; additionally, phenolic extracts from Aronia or grape juice were added. Blood samples were taken before ingestion of the bolus drink and 30, 60, 90, 120, 180, 240, and 360 min after. Additionally, continuously the peripheral glucose was measured using a commercially available sensor system. Results: In all ten volunteers, the intake of Aronia extract (100 mg) reduced both the peripheral glucose and the blood glucose levels significantly (p ≤ 0.05) in comparison to the control. Blood insulin levels were not affected. Whereas the intake of red grape extract (120 mg) did not reduce the glucose levels but increased the insulin levels significantly. Conclusion: Our pilot study showed that even low amounts of a phenolic Aronia extract could lower glucose absorption. Thus, due to the blood glucose-lowering effects of Aronia phenolics in healthy volunteers, these preliminary results warrant further investigation in the frame of a follow-up study with a larger number of volunteers.

scholarly journals Decreased Skin-Mediated Detoxification Contributes to Oxidative Stress and Insulin Resistance

2012 ◽  
Vol 2012 ◽  
pp. 1-9
Author(s):  
Xing-Xing Liu ◽  
Chang-Bin Sun ◽  
Ting-Tong Yang ◽  
Da Li ◽  
Chun-Yan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Toxic Substances ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucose Injection ◽  
Plasma Insulin Levels ◽  
Induced Changes ◽  
The Relationship

The skin, the body's largest organ, plays an important role in the biotransformation/detoxification and elimination of xenobiotics and endogenous toxic substances, but its role in oxidative stress and insulin resistance is unclear. We investigated the relationship between skin detoxification and oxidative stress/insulin resistance by examining burn-induced changes in nicotinamide degradation. Rats were divided into four groups: sham-operated, sham-nicotinamide, burn, and burn-nicotinamide. Rats received an intraperitoneal glucose injection (2 g/kg) with (sham-nicotinamide and burn-nicotinamide groups) or without (sham-operated and burn groups) coadministration of nicotinamide (100 mg/kg). The results showed that the mRNA of all detoxification-related enzymes tested was detected in sham-operated skin but not in burned skin. The clearance of nicotinamide andN1-methylnicotinamide in burned rats was significantly decreased compared with that in sham-operated rats. After glucose loading, burn group showed significantly higher plasma insulin levels with a lower muscle glycogen level than that of sham-operated and sham-nicotinamide groups, although there were no significant differences in blood glucose levels over time between groups. More profound changes in plasma H2O2and insulin levels were observed in burn-nicotinamide group. It may be concluded that decreased skin detoxification may increase the risk for oxidative stress and insulin resistance.

Plasma glucose and insulin responses in growing rats fed a total parenteral nutrition diet either intravenously or intragastrically

1984 ◽  
Vol 62 (7) ◽  
pp. 775-780 ◽  
Author(s):  
Norman S. Track ◽  
Ernest Cutz ◽  
Barbara H. Witt
Keyword(s):  
Amino Acid ◽  
Parenteral Nutrition ◽  
Total Parenteral Nutrition ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Glucose Levels ◽  
Group I ◽  
Plasma Insulin Levels ◽  
Group Ii ◽  
Insulin Responses

The effect of administering either intravenously (group I) or intragastrically (group II) a glucose – amino acid total parenteral nutrition diet over a 12-day period upon plasma glucose and insulin responses was examined in adolescent rats. Infusion of the 25% glucose – 12.2% amino acid diet at a rate of 300 kCal∙kg body weight−1∙24 h−1 supported normal weight gain over the 12-day study period in both intravenously (group I) and intragastrically (group II) alimented rats. Mean plasma glucose levels rose dramatically in both groups by the end of day 1; group I had significantly higher mean plasma insulin levels. By day 3, the group I mean plasma glucose value decreased significantly while the group II mean glucose value remained virtually unchanged. Mean plasma insulin values more than doubled in both groups with the group I level still remaining significantly above the group II level. At days 6 and 12, group I mean plasma glucose levels were significantly below group II while both groups had similar plasma insulin levels. Data from this 12-day intravenous–intragastric alimentation study reveals quite different metabolic responses compared with acute (120–180 min) studies of the enteroinsular axis.

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