scholarly journals Characterization and Comparison of Insulin Resistance Induced by Cushing Syndrome or Diestrus against Healthy Control Dogs as Determined by Euglycemic- Hyperinsulinemic Glucose Clamp Profile Glucose Infusion Rate Using an Artificial Pancreas Apparatus

2012 ◽  
Vol 74 (11) ◽  
pp. 1527-1530 ◽  
Author(s):  
Hiroko FUKUTA ◽  
Akihiro MORI ◽  
Nazarbek URUMUHAN ◽  
Peter LEE ◽  
Hitomi ODA ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Infusion Rate ◽  
Cushing Syndrome ◽  
Artificial Pancreas ◽  
Glucose Clamp ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Healthy Control

A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents

2007 ◽  
Vol 292 (5) ◽  
pp. E1358-E1363 ◽  
Author(s):  
Arvinder K. Dhalla ◽  
Mei Yee Wong ◽  
Peter J. Voshol ◽  
Luiz Belardinelli ◽  
Gerald M. Reaven
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Adenosine Receptor ◽  
Infusion Rate ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Oral Glucose ◽  
Acute Administration ◽  
High Fat ◽  
Adenosine Receptor Agonist

There is substantial evidence in the literature that elevated plasma free fatty acids (FFA) play a role in the pathogenesis of type 2 diabetes. CVT-3619 is a selective partial A1 adenosine receptor agonist that inhibits lipolysis and lowers circulating FFA. The present study was undertaken to determine the effect of CVT-3619 on insulin resistance induced by high-fat (HF) diet in rodents. HF diet feeding to rats for 2 wk caused a significant increase in insulin, FFA, and triglyceride (TG) concentrations compared with rats fed chow. CVT-3619 (1 mg/kg) caused a time-dependent decrease in fasting insulin, FFA, and TG concentrations. Acute administration of CVT-3619 significantly lowered the insulin response, whereas glucose response was not different with an oral glucose tolerance test. Treatment with CVT-3619 for 2 wk resulted in significant lowering of FFA, TG, and insulin concentrations in rats on HF diet. To determine the effect of CVT-3619 on insulin sensitivity, hyperinsulinemic euglycemic clamp studies were performed in C57BL/J6 mice fed HF diet for 12 wk. Glucose infusion rate was decreased significantly in HF mice compared with chow-fed mice. CVT-3619 treatment 15 min prior to the clamp study significantly ( P < 0.01) increased glucose infusion rate to values similar to that for chow-fed mice. In conclusion, CVT-3619 treatment lowers FFA and TG concentrations and improves insulin sensitivity in rodent models of insulin resistance.

scholarly journals Ginsenoside Re Reduces Insulin Resistance through Inhibition of c-Jun NH2-Terminal Kinase and Nuclear Factor-κB

2008 ◽  
Vol 22 (1) ◽  
pp. 186-195 ◽  
Author(s):  
Zhiguo Zhang ◽  
Xiaoying Li ◽  
Wenshan Lv ◽  
Yisheng Yang ◽  
Hong Gao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Infusion Rate ◽  
Glucose Infusion ◽  
Signaling Cascades ◽  
Glucose Infusion Rate ◽  
Nuclear Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Ginsenoside Re

Abstract Ginsenoside Re (Re), a compound derived from Panax ginseng, shows an antidiabetic effect. However, the molecular basis of its action remains unknown. We investigated insulin signaling and the antiinflammatory effect by Re in 3T3-L1 adipocytes and in high-fat diet (HFD) rats to dissect its anti-hyperglycemic mechanism. Glucose uptake was measured in 3T3-L1 cells and glucose infusion rate determined by clamp in HFD rats. The insulin signaling cascade, including insulin receptor (IR) β-subunit, IR substrate-1, phosphatidylinositol 3-kinase, Akt and Akt substrate of 160 kDa, and glucose transporter-4 translocation are examined. Furthermore, c-Jun NH2-terminal kinase (JNK), MAPK, and nuclear factor (NF)-κB signaling cascades were also assessed. The results show Re increases glucose uptake in 3T3-L1 cells and glucose infusion rate in HFD rats. The activation of insulin signaling by Re is initiated at IR substrate-1 and further passes on through phosphatidylinositol 3-kinase and downstream signaling cascades. Moreover, Re demonstrates an impressive suppression of JNK and NF-κB activation and inhibitor of NF-κBα degradation. In conclusion, Re reduces insulin resistance in 3T3-L1 adipocytes and HFD rats through inhibition of JNK and NF-κB activation.

scholarly journals Oxidative Stress Is Associated with Adiposity and Insulin Resistance in Men

2003 ◽  
Vol 88 (10) ◽  
pp. 4673-4676 ◽  
Author(s):  
Hideki Urakawa ◽  
Akira Katsuki ◽  
Yasuhiro Sumida ◽  
Esteban C. Gabazza ◽  
Shuichi Murashima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Body Mass Index ◽  
Body Mass ◽  
Body Fat ◽  
Plasma Levels ◽  
Infusion Rate ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Total Fat

Abstract To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2α (PGF2α) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2α than nonobese men (P &lt; 0.05). The plasma levels of 8-epi-PGF2α were significantly correlated with body mass index (r = 0.408; P &lt; 0.05), body fat weight (r = 0.467; P &lt; 0.05), visceral (r = 0.387; P &lt; 0.05) and total fat area (r = 0.359; P &lt; 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2α and glucose infusion rate in obese men (r = −0.552; P &lt; 0.05) and all men (r = −0.668; P &lt; 0.01). In all subjects, the plasma levels of 8-epi-PGF2α were significantly correlated with fasting serum levels of insulin (r = 0.487; P &lt; 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2α are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.

Insulin responsiveness, action and sensitivity in growing lambs and mature rams

1996 ◽  
Vol 76 (2) ◽  
pp. 203-208 ◽  
Author(s):  
H. Sano ◽  
K. Asanos ◽  
Y. Noguchi ◽  
K. Yoshimura ◽  
T. Senshu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Infusion Rate ◽  
Plasma Insulin ◽  
Glucose Clamp ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Clamp Technique ◽  
Glucose Clamp Technique ◽  
Insulin Responsiveness ◽  
Blood Glucose Concentrations

Insulin responsiveness, action and sensitivity, using the glucose clamp technique, were measured in ruminating growing lambs (5 and 9 mo old) and mature rams (3 yr old). In the hyperglycemic clamp experiment, blood glucose concentrations were designed to remain 50 mg dL−1 above basal concentrations for more than 1 h. Plasma insulin concentrations during glucose infusion were lower (P < 0.05) for 5 mo-old lambs than for 9 mo-old lambs and mature rams and were higher (P < 0.05) for 9 mo-old lambs than for 5 mo-old lambs and mature rams. In the hyperinsulinemic euglycemic clamp experiment, insulin was infused over five sequential 1-h periods at rates from 0.64 to 25 mU kg−1 min−1 with concomitant glucose infusion to maintain preinfusion blood glucose concentrations. Glucose infusion rates during insulin infusion were lower (P < 0.05) for 5 mo-old lambs than for 9 mo-old lambs and plasma insulin concentration at half-maximal glucose infusion rate was numerically lower for 5 mo-old lambs, whereas maximal glucose infusion rate did not differ among growth stages. It is likely that in ruminating sheep insulin responsiveness, action and sensitivity may change with growth stage. Key words: Development, insulin response, insulin sensitivity, sheep, glucose clamp technique

Quantity of sucrose alters the tissue pattern and time course of insulin resistance in young rats

1995 ◽  
Vol 269 (3) ◽  
pp. R641-R646 ◽  
Author(s):  
M. J. Pagliassotti ◽  
P. A. Prach
Keyword(s):  
Insulin Resistance ◽  
Total Energy ◽  
Infusion Rate ◽  
Time Course ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Young Rats ◽  
Sucrose Diet

To determine the effects of the amount of sucrose in the diet on insulin-stimulated glucose metabolism, euglycemic hyperinsulinemic clamps were performed on male Wistar rats after one of the following dietary treatments (n = 6-8/treatment): 1) high-starch diet (68% of total energy) for 8 wk (ST8), 16 wk (ST16), or 30 wk (ST30); 2) high-sucrose diet (68% of total energy) for 8 wk (SU8), 16 wk (SU16), or 30 wk (SU30); or 3) low-sucrose diet (18% of total energy) for 8 wk (SUL8), 16 wk (SUL16), or 30 wk (SUL30). Body weights were similar in starch- and sucrose-fed rats at 8 wk (502 +/- 9 g), 16 wk (563 +/- 10 g), and 30 wk (607 +/- 26 g). The glucose infusion rate (mumol.g-1.min-1) required to maintain similar glycemia during clamps was 73.1 +/- 8.8 in ST8, 29.7 +/- 4.9 in SU8 (P < 0.05 vs. ST8 and SUL8), and 76.4 +/- 8.2 in SUL8; 69.9 +/- 8.1 in ST16, 35.1 +/- 5.1 in SU16 (P < 0.05 vs. ST16 and SUL16), and 63.2 +/- 6.5 in SUL16; and 65.4 +/- 7.7 in ST30, 26.0 +/- 5.3 (P < 0.05 vs. ST30), and 36.3 +/- 6.0 in SUL30 (P < 0.05 vs. ST30). Impaired suppression of hepatic glucose production accounted for 43, 39, and 34% of the decrease in the glucose infusion rate in SU8 compared with ST8, SU16 compared with ST16, and SU30 compared with ST30, respectively, but 78% in SUL30 compared with ST30. These results suggest that both high- and low-sucrose diets can produce insulin resistance in young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma glucose concentration determines direct versus indirect liver glycogen synthesis

1986 ◽  
Vol 251 (5) ◽  
pp. E584-E590 ◽  
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
H. L. Blakesley ◽  
J. L. Johnson ◽  
J. J. Spitzer
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Infusion Rate ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Hepatic Glycogen ◽  
Glucose Load ◽  
Indirect Pathway

In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.

scholarly journals Effects of supplemental chromium and heat exposure on glucose metabolism and insulin action in sheep

2000 ◽  
Vol 134 (3) ◽  
pp. 319-325 ◽  
Author(s):  
H. SANO ◽  
S. KONNO ◽  
A. SHIGA
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Infusion Rate ◽  
Insulin Action ◽  
Heat Exposure ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Isotope Dilution Method ◽  
Glucose Turnover ◽  
Dilution Method

An isotope dilution method using [U-13C]glucose and a glucose clamp approach were applied to determine the effects of supplemental chromium (Cr) and heat exposure on blood glucose metabolism and tissue responsiveness and sensitivity to insulin in sheep. The sheep consumed diets with either 0 or 1 mg of Cr/kg (Control and +Cr diet, respectively) from high-Cr-yeast, and were exposed from a thermoneutral environment (20 °C) to a hot environment (30 °C) for 5 days. Blood glucose turnover rate did not differ between the diets, and was lower (P < 0·05) during heat exposure than in the thermoneutral environment. The maximal glucose infusion rate (tissue responsiveness to insulin) tended to be lower (P = 0·06) for the +Cr diet than for the Control diet, but did not change with heat exposure. The plasma insulin concentration at half maximal glucose infusion rate (tissue sensitivity to insulin) did not differ between the diets, and was greater (P < 0·05) during heat exposure than in the thermoneutral environment. No significant diet × environment interactions were observed. There was no significant evidence that Cr supplementation moderated heat stress in sheep from the measures of blood glucose metabolism and insulin action.

Effects of FFA on insulin-stimulated glucose fluxes and muscle glycogen synthase activity in rats

1998 ◽  
Vol 275 (2) ◽  
pp. E338-E344 ◽  
Author(s):  
Joong-Yeol Park ◽  
Chul-Hee Kim ◽  
Sung K. Hong ◽  
Kyo I. Suh ◽  
Ki-Up Lee
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Infusion Rate ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Whole Body ◽  
Heparin Infusion ◽  
Muscle Glycogen Synthesis

To examine effects of free fatty acids (FFA) on insulin-stimulated glucose fluxes, euglycemic hyperinsulinemic (86 pmol ⋅ kg−1 ⋅ min−1) clamps were performed for 5 h in conscious rats with ( n = 8) or without ( n = 8) lipid-heparin infusion. Glucose infusion rate required to maintain euglycemia was not different between the two groups during the first 2 h of clamps but became significantly lower with lipid-heparin infusion in the 3rd h and thereafter. To investigate changes in intracellular glucose metabolism during lipid-heparin infusion, additional clamps ( n = 8 each) were performed for 1, 2, 3, or 5 h with an infusion of [3-3H]glucose. Insulin-stimulated whole body glucose utilization (Rd), glycolysis, and glycogen synthesis were estimated on the basis of tracer concentrations in plasma during the final 40 min of each clamp. Similar to changes in glucose infusion rate, Rd was not different between the two groups in the 1st and 2nd h but was significantly lower with lipid-heparin infusion in the 3rd h and thereafter. Whole body glycolysis was significantly lower with lipid-heparin infusion in all time periods, i.e., 1st, 2nd, 3rd, and 5th h of clamps. In contrast, whole body glycogen synthesis was higher with lipid-heparin infusion in the 1st and 2nd h but lower in the 5th h. Similarly, accumulation of [3H]glycogen radioactivity in muscle glycogen was significantly higher with lipid-heparin during the 1st and 2nd h but lower during the 3rd and 5th h. Glucose 6-phosphate (G-6- P) concentrations in gastrocnemius muscles were significantly higher with lipid-heparin infusion throughout the clamps. Muscle glycogen synthase (GS) activity was not altered with lipid-heparin infusion at 1, 2, and 3 h but was significantly lower at 5 h. Thus increased availability of FFA significantly reduced whole body glycolysis, but compensatory increase in skeletal muscle glycogen synthesis in association with accumulation of G-6- P masked this effect, and Rd was not affected in the early phase (within 2 h) of lipid-heparin infusion. Rd was reduced in the later phase (>2 h) of lipid-heparin infusion, when glycogen synthesis was reduced in association with reduced skeletal muscle GS activity.

scholarly journals The Insulin-Sensitizing Effect of Rosiglitazone in Type 2 Diabetes Mellitus Patients Does Not Require Improved in Vivo Muscle Mitochondrial Function

2008 ◽  
Vol 93 (7) ◽  
pp. 2917-2921 ◽  
Author(s):  
Vera B. Schrauwen-Hinderling ◽  
Marco Mensink ◽  
Matthijs K. C. Hesselink ◽  
Jean-Pierre Sels ◽  
M. Eline Kooi ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Mitochondrial Function ◽  
Infusion Rate ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Diabetic Patients ◽  
Half Time ◽  
Sensitizing Effect

Abstract Aims: Our objective was to investigate whether improved in vivo mitochondrial function in skeletal muscle and intramyocellular lipids (IMCLs) contribute to the insulin-sensitizing effect of rosiglitazone. Methods: Eight overweight type 2 diabetic patients (body mass index = 29.3 ± 1.1 kg/m2) were treated with rosiglitazone for 8 wk. Before and after treatment, insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Muscular mitochondrial function (half-time of phosphocreatine recovery after exercise) and IMCL content were measured by magnetic resonance spectroscopy. Results: Insulin sensitivity improved after rosiglitazone (glucose infusion rate: 19.9 ± 2.8 to 24.8 ± 2.1 μmol/kg·min; P &lt; 0.05). In vivo mitochondrial function (phosphocreatine recovery half-time: 23.8 ± 3.5 to 20.0 ± 1.7 sec; P = 0.23) and IMCL content (0.93 ± 0.18% to 1.37 ± 0.40%; P = 0.34) did not change. Interestingly, the changes in PCr half-time correlated/tended to correlate with changes in fasting insulin (R2 = 0.50; P = 0.05) and glucose (R2 = 0.43; P = 0.08) levels. Changes in PCr half-time did not correlate with changes in glucose infusion rate (R2 = 0.08; P = 0.49). Conclusion: The rosiglitazone-enhanced insulin sensitivity does not require improved muscular mitochondrial function.

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