Development of Decreased Insulin-Induced Glucose Transport in Skeletal Muscle of Glucose-Intolerant Hybrids of Diabetic GK Rats

1995 ◽  
Vol 88 (3) ◽  
pp. 301-306 ◽  
Author(s):  
Lorraine A. Nolte ◽  
Samy M. Abdel-Halim ◽  
Iva K. Martin ◽  
Amel Guenifi ◽  
Juleen R. Zierath ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucose Transport ◽  
Glucose Intolerance ◽  
Dose Response ◽  
Insulin Dose ◽  
Age Groups ◽  
Plasma Free Fatty Acid ◽  
Response Curves ◽  
And Control

1. The effect of glucose intolerance on insulin-stimulated glucose transport in isolated skeletal muscles was investigated in male F, hybrids of spontaneously diabetic GK (Goto—Kakizaki) and control Wistar rats at 1 and 2 months of age. 2. Hybrid rats are characterized by markedly impaired glucose-induced insulin secretion. The area under the blood glucose curve was significantly higher following an intraperitoneal glucose injection (2 g/kg) in hybrid rats in both age groups than in the control rats (P < 0.001). In 2-month-old hybrid rats the incremental area under the insulin curve during the intraperitoneal glucose tolerance test was not different from that of control rats. Serum cholesterol, triacylglycerol or plasma free fatty acid levels did not differ between the groups. Fasting and post-prandial plasma glucose concentrations were elevated in 2-month-old hybrid rats compared with control rats (54%, P < 0.05, and 27%, P < 0.05, respectively), but were not differerent in 1-month-old rats. Plasma insulin did not differ between the hybrid and control rats in the fasting or post-prandial state at either age studied. 3. The insulin dose—response curves for 3-O-methylglucose transport did not differ between 1-month-old hybrid and control rats for either the soleus or epitrochlearis muscle. The insulin dose—response curve for the epitrochlearis, but not for the soleus, muscle from 2-month-old hybrid rats was shifted to the right compared with the curve from the control animals (P < 0.05). 4. In conclusion, the hybrid rat is a non-obese, non-hyperinsulinaemic animal model, which at a young age is characterized by impaired insulin secretion and moderate glucose intolerance. In this glucose-intolerant rat model, mild peripheral insulin resistance gradually develops, as reflected by the decreased insulin-induced glucose transport in the fast-twitch epitrochlearis muscle. It is suggested that the elevated blood glucose per se may have contributed to the slight decrease in peripheral insulin action.

Dissociation of effects of insulin and contraction on glucose transport in rat epitrochlearis muscle

1985 ◽  
Vol 249 (3) ◽  
pp. C226-C232 ◽  
Author(s):  
R. Nesher ◽  
I. E. Karl ◽  
D. M. Kipnis
Keyword(s):  
Glucose Transport ◽  
Dose Response ◽  
Isometric Contraction ◽  
Insulin Dose ◽  
Diabetic Rats ◽  
Maximal Rate ◽  
Minimal Effect ◽  
Hexose Transport ◽  
Response Curves

The effects of insulin and contraction on glucose transport and metabolism were investigated in rat epitrochlearis muscles in vitro. Insulin dose-response curves showed a threshold (approximately 50 microunits/ml) and saturation-type (approximately 1 mU/ml) kinetics, whereas isometric contraction activated glucose transport and metabolism in a linear fashion with no evidence of a threshold. Insulin and contraction increased the apparent maximal rate of uptake of the hexose transport system with minimal effect on its apparent Km. The stimulatory effects of insulin and contraction were additive; similar results were obtained with 2-deoxy-D-glucose. Contraction stimulated glucose transport in three different preparations of muscles depleted of insulin: 1) exhaustively washed for 2 h, 2) rats infused with anti-insulin serum, and 3) chronically (streptozotocin-induced) diabetic rats. Prostaglandin E2 augmented the effect of a submaximal concentration of insulin on glucose transport without exerting any effect by itself but had no effect on contraction-augmented glucose transport. It is concluded that insulin and contraction activate glucose transport and metabolism via independent mechanisms.

scholarly journals Bioindicator demonstrates high persistence of sulfentrazone in dry soil1

2015 ◽  
Vol 45 (3) ◽  
pp. 326-332 ◽  
Author(s):  
Renato Coradello Lourenço ◽  
Saul Jorge Pinto de Carvalho
Keyword(s):  
Dose Response ◽  
Residual Effect ◽  
Second Phase ◽  
Response Curves ◽  
Sugarcane Crop ◽  
Phytotoxic Activity ◽  
Dry Soil ◽  
Two Phases ◽  
Preemergence Herbicides ◽  
And Control

ABSTRACTIn sugarcane crop areas, the application of preemergence herbicides with long residual effect in the soil has been frequently necessary. The herbicide persistence in the soil must be high especially because of applications during the dry season of the year, after sugarcane harvest. This study aimed at estimating the sulfentrazone persistence and dissipation in dry soil using bioindicator. Five experiments were carried out, divided into two phases. In the first phase, three dose-response curves were adjusted to select the best bioindicator to be adopted in the second phase. Niger was adopted due to its lower sensibility to sulfentrazone. In the second phase, a new dose-response curve was carried out, with six doses of sulfentrazone, in order to standardize the bioindicator sensibility to sulfentrazone. At the end, another experiment with six periods of sulfentrazone persistence in dry clay soil was developed. Persistence periods were: 182, 154, 125, 98 and 30 days. The bioindicator was seeded at the application day in treated plots and control. In this experiment, the sulfentrazone dose applied was 800 g ha-1. Niger was considered a good species to estimate the sulfentrazone persistence in dry soil. The sulfentrazone phytotoxic activity was identified up to 182 days after application, and its average dissipation rate was 2.15 g ha-1 day-1, with half-life higher than 182 days.

The effect of prostaglandin E1 upon the pressor and hormonal response to exogenous angiotensin II in human pregnancy

1987 ◽  
Vol 72 (3) ◽  
pp. 351-357 ◽  
Author(s):  
F. Broughton Pipkin ◽  
R. Morrison ◽  
P. M. S. O'Brien
Keyword(s):  
Blood Pressure ◽  
Dose Response ◽  
Prostaglandin E1 ◽  
Age Groups ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Hormonal Response ◽  
Response Curves ◽  
Basal Blood Pressure ◽  
Dose Response Curves

1. The effect of prostaglandin E1 (PGE1) on the pressor and hormonal response to angiotensin (ANG) II has been studied in 22 women in second trimester pregnancy. Three-point dose–response curves were initially determined for all women. Eleven then received an infusion of PGE1 while the remainder received an infusion of normal saline as controls. The dose–response curves to ANG II were re-studied after a period of stabilization. 2. Although assignation to treatment group was random, differences were found in age and basal blood pressure between the control group and those given PGE1. The pressor data from the PGE1 group were thus split by age for analysis. 3. The administration of ANG II alone was associated with significant (P<0.001 at all doses) pressor effects without accompanying bradycardia. Plasma renin concentration (PRC) was suppressed (P<0.001). Plasma aldosterone concentration rose (P<0.001), the magnitude of the rise being directly associated with the plasma ANG II concentrations achieved (P<0.05). 4. The infusion of PGE, had no significant effect on basal blood pressure, but evoked a sustained tachycardia in both age groups (P<0.001). Basal hormone concentrations were unchanged. 5. The pressor response to ANG II was blunted in the presence of PGE1, in both age groups, the overall effect being greatest when the initial response had been large (P<0.05). Measured plasma concentrations of ANG II were lower under these circumstances (P<0.02). PRC fell (P<0.05 for both groups) and plasma aldosterone concentrations rose (P<0.005 for the treated and P<0.001 for the control groups), but the magnitude of these changes did not differ significantly in the two groups. 6. These data support the hypothesis of a for the vasodilator prostaglandins in minimizing the potential pressor effects of the raised ANG II concentrations seen in pregnancy.

Improvement in Glycemic Control in Mice of Different Age Groups

2019 ◽  
Author(s):  
Suhadinie Gamage ◽  
Swetha Peddibhotla ◽  
P. Hemachandra Reddy ◽  
Nikhil V. Dhurandhar ◽  
Vijay Hegde
Keyword(s):  
Blood Glucose ◽  
Glycemic Control ◽  
Glucose Intolerance ◽  
Serum Insulin ◽  
Age Groups ◽  
Tolerance Test ◽  
Chow Diet ◽  
Control Blood Glucose ◽  
Beneficial Effects ◽  
Old Mice

Abstract Aims and Methods The declining ability to control blood glucose with advancement of age is an important health risk factor and may lead to insulin resistance, type-2-diabetes and Alzheimer’s disease. Adenovirus 36(Ad36) improves glycemic control independent of insulin signaling(insulin sparing effect) as evidenced by cell, animal and observational human studies. This property of Ad36 may be useful in correcting aging-related glucose intolerance and related health conditions. Therefore, we determined the effect of Ad36 on glycemic control in older mice, to identify the age group that best responds to Ad36. Six, 12 or 20-month old C57Bl/6 mice on chow diet were each divided into weight-matched groups(mock-infected or Ad36-infected). Body weight was recorded weekly post infection (p.i.) and fasting glucose measured(week 0, 4, 8 and 20 p.i.). Blood glucose and serum insulin were measured during glucose tolerance test(week 0 and 16 p.i.). At week 20 p.i., animals were sacrificed, blood and tissues collected. Results Mice from all age groups showed improvement in glucose clearance post Ad36 infection, but a more profound effect was observed in 6-month old mice compared with mock-infected mice. Under fed conditions though there was no difference in blood glucose at 20 wk p.i., interestingly, Ad36 reduced serum insulin in age groups old mice, compared with control mice. Conclusions These findings suggest Ad36 infected animals improve glycemic control and clear post-prandial gluco00000se increase without increasing insulin secretion in an insulin sparing manner. These beneficial effects provide strong evidence for developing Ad36-based approaches as a novel tool to attenuate age associated glucose intolerance.

GLUCOSE TOLERANCE AND IMMUNOREACTIVE INSULIN IN PATIENTS WITH PHEOCHROMOCYTOMA: THE EFFECT OF α-RECEPTOR BLOCKING AGENTS

1971 ◽  
Vol 66 (2) ◽  
pp. 368-378 ◽  
Author(s):  
Ruth Illig ◽  
W. H. Ziegler
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Metastatic Tumour ◽  
Oral Glucose ◽  
Surgical Removal ◽  
Receptor Blockade ◽  
Receptor Blocking ◽  
Control Subjects ◽  
And Control

ABSTRACT Blood glucose, plasma insulin, free fatty acids and urinary noradrenaline were investigated in 5 patients with noradrenaline producing pheochromocytoma (4 adenomas, 1 metastatic tumour) and in 3 control subjects. Oral glucose tolerance tests were performed before therapy, during treatment with the α-receptor blocking agent phenoxybenzamine, and in 4 patients after surgical removal of the tumour. In the untreated pheochromocytoma patients, glucose curves were pathologically high; insulin secretion was low in relation to blood glucose levels or almost completely suppressed depending on the plasma noradrenaline concentrations. During phenoxybenzamine treatment glucose curves remained abnormal; insulin concentrations increased both in patients and control subjects. Six to 26 days after operation, glucose curves and insulin secretion became normal. Fractionated urine collections revealed a fall in noradrenaline excretion after oral glucose load. The urinary excretion of noradrenaline increased when α-receptor blockade was effective. The increased release of insulin under α-receptor blockade in patients and control subjects suggests that noradrenaline plays a role in the regulation of insulin secretion in normal conditions as well as in patients with pheochromocytoma.

DIMINISHED SENSITIVITY OF THE INSULIN RESPONSE TO GLUCOSE FOLLOWING GROWTH HORMONE INFUSION IN MAN

1976 ◽  
Vol 81 (4) ◽  
pp. 735-742 ◽  
Author(s):  
Ulf Adamson ◽  
Erol Cerasi
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Insulin Release ◽  
Dose Response ◽  
Plasma Insulin ◽  
Insulin Dose ◽  
Insulin Response ◽  
Insulinogenic Index ◽  
K Value ◽  
Insulin Response To Glucose

ABSTRACT The acute effect of growth hormone (GH) administration on the dose-kinetics of glucose-stimulated insulin release was investigated in eight healthy, non-obese male subjects. The glucose-insulin dose-response relationship in these subjects was established by performing glucose infusions at three different dose levels. In a second series of experiments, the glucose infusions were preceded by a 30 min infusion of GH (40 μg/kg body weight), terminated 60 min before administration of glucose. GH induced small but significant reductions in the basal levels of blood glucose and plasma insulin. The glucose tolerance (k-value) was diminished after GH at all glucose doses. Both the initial late phases of insulin response to glucose were impaired following GH treatment. This effect was most pronounced when the intermediary glucose dose (eliciting a blood glucose level around 300 mg/100 ml) was used. Thus, the insulinogenic index (whole period of stimulation) was reduced by GH to 88.9 ± 7.6, 60.4 ± 7.1 and 74.3 ± 11.0% of the respective controls when the smallest, the intermediate, and the largest glucose loads, respectively, were given. The blood glucose-plasma insulin dose-response curves were shifted to the right of the control ones when glucose infusion was preceded by GH. These findings suggest that GH diminishes the sensitivity of the islet for the insulin releasing action of glucose. Some possible mechanisms by which GH may modify insulin release are discussed.

Fat metabolism in human obesity

1994 ◽  
Vol 266 (4) ◽  
pp. E600-E605 ◽  
Author(s):  
P. J. Campbell ◽  
M. G. Carlson ◽  
N. Nurjhan
Keyword(s):  
Insulin Resistance ◽  
Fat Mass ◽  
Dose Response ◽  
Insulin Dose ◽  
Fat Free Mass ◽  
Maximal Response ◽  
Response Curves ◽  
Ffa Metabolism ◽  
Obese Subjects ◽  
The Right

Excessive fat turnover and oxidation might cause the insulin resistance of carbohydrate metabolism in obese humans. We studied the response of free fatty acid (FFA) metabolism in lean and obese volunteers to sequential insulin infusions of 4, 8, 25, and 400 mU.m-2.min-1. The insulin dose-response curves for suppression of FFA concentration, FFA turnover ([1-14C]palmitate), and lipolysis ([2H5]glycerol) were shifted to the right in the obese subjects (insulin concentrations that produced a half-maximal response, lean vs. obese: 103 +/- 21 vs. 273 +/- 41, 96 +/- 11 vs. 264 +/- 44, and 101 +/- 23 vs. 266 +/- 44 pM, all P < 0.05), consistent with insulin resistance of FFA metabolism in obesity. After the overnight fast, FFA turnover per fat mass was decreased in obese subjects (37 +/- 4 vs. 20 +/- 3 mumol.kg fat mass-1.min-1, P < 0.01) as the result of suppression of lipolysis by the hyperinsulinemia of obesity and an increased fractional reesterification of FFA before leaving the adipocyte (primary FFA reesterification; 0.14 +/- 0.03 vs. 0.35 +/- 0.06, P < 0.05). Nevertheless, FFA turnover per fat-free mass (FFM) was also greater in the obese volunteers (8.5 +/- 0.7 vs. 11.0 +/- 1.0 mumol.kg FFM-1.min-1, P < 0.05) but only as the result of increased reesterification of intravascular FFA (secondary reesterification; 1.8 +/- 0.5 vs. 4.8 +/- 1.1 mumol.kg FFM-1.min-1, P < 0.01), since FFA oxidation was the same in the two groups throughout the insulin dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of the febrile responses of rats to endogenous pyrogen occurs within the OVLT region

1989 ◽  
Vol 67 (5) ◽  
pp. 1740-1746 ◽  
Author(s):  
J. T. Stitt ◽  
S. G. Shimada
Keyword(s):  
Dose Response ◽  
Standard Dose ◽  
Muramyl Dipeptide ◽  
The Body ◽  
Prostaglandin E ◽  
Sprague Dawley ◽  
Endogenous Pyrogen ◽  
Response Curves ◽  
Hypothalamic Area ◽  
And Control

The febrile responses of male Sprague-Dawley rats to a semi-purified endogenous pyrogen (EP) derived from human monocytes are markedly enhanced 3 days after the animals are intravenously injected with a variety of immunoadjuvants. The present study was designed to investigate the site within the body at which these substances act to produce this febrile-enhancing phenomenon. Stainless steel microinjection cannula guide tubes were implanted within the region of the organum vasculosum lamina terminalis (OVLT) of the rats and control febrile dose-response curves to EP were established. Minute quantities of the immunoadjuvants zymosan, lipopolysaccharide endotoxin, and the synthetic adjuvant peptide, muramyl dipeptide, were microinjected into the OVLT region and 3 days later, the febrile responses of the animals were retested. In each case the febrile response elicited by a standard dose of EP was more than doubled, the slope of the fever dose-response curve was tripled, and the dose threshold was lowered by a factor of four to five. These responses are identical with those produced when much larger amounts of these immunoadjuvants are injected intravenously, and, thus, we conclude that the site of action of these substances in enhancing fever in response to EP resides in or near the OVLT region. It is proposed that EP stimulates a type of reticuloendothelial cell residing within the OVLT to release prostaglandin E, which in turn crosses the blood-brain barrier to effect the changes in the thermoregulatory neurons of the preoptic anterior hypothalamic area that result in fever.

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