scholarly journals Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats

Diabetologia ◽  
1999 ◽  
Vol 42 (11) ◽  
pp. 1324-1331 ◽  
Author(s):  
B. Balkan ◽  
L. Kwasnik ◽  
R. Miserendino ◽  
J. J. Holst ◽  
X. Li
Keyword(s):  
Glucose Tolerance ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Obese Zucker Rats

scholarly journals Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats

2005 ◽  
Vol 153 (6) ◽  
pp. 963-969 ◽  
Author(s):  
Dorte X Gram ◽  
Anker J Hansen ◽  
Michael Wilken ◽  
Torben Elm ◽  
Ove Svendsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Nerve Activity ◽  
Calcitonin Gene ◽  
Obese Rats ◽  
Obese Zucker Rats

Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity – and therefore might be involved in the pathophysiology – is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1±3.4 pmol/l in pre-obese Zucker rats vs 6.9±1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3±0.2 mmol/l vs 5.1±0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8±0.3 mmol/l vs 8.6±0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.

Insulin resistance of obese Zucker rats exercise trained at two different intensities

1991 ◽  
Vol 261 (5) ◽  
pp. E613-E619 ◽  
Author(s):  
M. Y. Cortez ◽  
C. E. Torgan ◽  
J. T. Brozinick ◽  
J. L. Ivy
Keyword(s):  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Citrate Synthase ◽  
Exercise Group ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Equal Work ◽  
Obese Zucker Rats ◽  
Fast Twitch

The effect of exercise intensity on oral glucose tolerance and hindlimb glucose uptake and transport was studied in 26 female obese Zucker rats after a treadmill training program. The rats were randomly assigned to either a low-intensity (LI) or high-intensity (HI) exercise group, with equal work being performed by the two groups. A third group of rats served as sedentary controls (SED). The trained rats demonstrated a significant improvement in oral glucose tolerance while maintaining significantly lower plasma insulin concentrations when compared with the SED rats. However, no significant differences in plasma glucose or insulin concentrations were observed between the LI and HI exercise-trained groups. During hindlimb perfusion (500 microU/ml insulin, 8 mM glucose), the rate of muscle glucose uptake for the HI rats (13.5 +/- 0.8 mumol.h-1.g-1) was significantly faster than that of the LI rats (11.4 +/- 0.8 mumol.h-1.g-1), which was significantly faster than that of the SED rats (8.3 +/- 0.6 mumol.h-1.g-1). The rates of 3-O-methyl-D-glucose (3-MG) transport were substantially greater in the fast-twitch red fibers of the HI (10.11 +/- 0.49 mumol.h-1.g-1) and LI (9.08 +/- 0.46 mumol.h-1.g-1) rats when compared with those of the SED rats (6.15 +/- 0.41 mumol.h-1.g-1). However, only the HI training resulted in a significant increase in the 3-MG transport of the fast-twitch white fibers (HI, 2.37 +/- 0.27; LI, 1.48 +/- 0.11; SED, 1.31 +/- 0.15 mumol.h-1.g-1). Only muscles with an increased citrate synthase activity demonstrated an improved insulin-stimulated glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensory nerve inactivation by resiniferatoxin improves insulin sensitivity in male obese Zucker rats

2005 ◽  
Vol 288 (6) ◽  
pp. E1137-E1145 ◽  
Author(s):  
Sophia G. Moesgaard ◽  
Christian L. Brand ◽  
Jeppe Sturis ◽  
Bo Ahrén ◽  
Michael Wilken ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats

Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves (desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.05 mg/kg RTX sc given at ages 8, 10, and 12 wk), fasting plasma insulin was reduced ( P < 0.0005), and oral glucose tolerance was improved ( P < 0.005). Pancreas perfusion showed that baseline insulin secretion (7 mM glucose) was lower in RTX-treated rats ( P = 0.01). Insulin secretory responsiveness to 20 mM glucose was enhanced in the perfused pancreas of RTX-treated rats ( P < 0.005) but unaffected in stimulated, isolated pancreatic islets. At the peak of spontaneous insulin resistance in the obese Zucker rat, insulin sensitivity was substantially improved after RTX treatment, as evidenced by higher glucose infusion rates (GIR) required to maintain euglycemia during a hyperinsulinemic euglycemic (5 mU·kg−1·min−1) clamp (GIR60–120min: 5.97 ± 0.62 vs. 11.65 ± 0.83 mg·kg−1·min−1 in RTX-treated rats, P = 0.003). In conclusion, RTX treatment and, hence, sensory nerve desensitization of adult male obese Zucker rats improved oral glucose tolerance by enhancing insulin secretion, and, in particular, by improving insulin sensitivity.

Effects of exercise training and ACE inhibition on insulin action in rat skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 687-694 ◽  
Author(s):  
Kara R. Foianini ◽  
Michelle S. Steen ◽  
Tyson R. Kinnick ◽  
Melanie B. Schmit ◽  
Erik B. Youngblood ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Insulin Action ◽  
Ace Inhibitor ◽  
Interactive Effect ◽  
Ace Inhibition ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

Our laboratory has demonstrated (Steen MS, Foianini KR, Youngblood EB, Kinnick TR, Jacob S, and Henriksen EJ, J Appl Physiol 86: 2044–2051, 1999) that exercise training and treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril interact to improve insulin action in insulin-resistant obese Zucker rats. The present study was undertaken to determine whether a similar interactive effect of these interventions is manifest in an animal model of normal insulin sensitivity. Lean Zucker ( Fa/−) rats were assigned to either a sedentary, trandolapril-treated (1 mg · kg−1 · day−1 for 6 wk), exercise-trained (treadmill running for 6 wk), or combined trandolapril-treated and exercise-trained group. Exercise training alone or in combination with trandolapril significantly ( P < 0.05) increased peak oxygen consumption by 26–32%. Compared with sedentary controls, exercise training alone or in combination with ACE inhibitor caused smaller areas under the curve for glucose (27–37%) and insulin (41–44%) responses during an oral glucose tolerance test. Exercise training alone or in combination with trandolapril also improved insulin-stimulated glucose transport in isolated epitrochlearis (33–50%) and soleus (58–66%) muscles. The increases due to exercise training alone or in combination with trandolapril were associated with enhanced muscle GLUT-4 protein levels and total hexokinase activities. However, there was no interactive effect of exercise training and ACE inhibition observed on insulin action. These results indicate that, in rats with normal insulin sensitivity, exercise training improves oral glucose tolerance and insulin-stimulated muscle glucose transport, whereas ACE inhibition has no effect. Moreover, the beneficial interactive effects of exercise training and ACE inhibition on these parameters are not apparent in lean Zucker rats and, therefore, are restricted to conditions of insulin resistance.

Tesaglitazar, a dual PPARα/γ agonist, ameliorates glucose and lipid intolerance in obese Zucker rats

2005 ◽  
Vol 289 (4) ◽  
pp. R938-R946 ◽  
Author(s):  
Nicholas D. Oakes ◽  
Pia Thalén ◽  
Therese Hultstrand ◽  
Severina Jacinto ◽  
Germán Camejo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Glucose Tolerance ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Therapeutic Effects ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Mass Load ◽  
Obese Zucker Rats

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor α/γ agonist, tesaglitazar, 3 μmol·kg−1·day−1 for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

scholarly journals Improved functional vasodilation in obese Zucker rats following exercise training

2011 ◽  
Vol 301 (3) ◽  
pp. H1090-H1096 ◽  
Author(s):  
Mohamad Sebai ◽  
Silu Lu ◽  
Lusha Xiang ◽  
Robert L. Hester
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Tolerance Test ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Global Effect ◽  
Thromboxane Receptor ◽  
Improve Insulin Resistance ◽  
Obese Zucker Rats

Obese individuals exhibit impaired functional vasodilation and exercise performance. We have demonstrated in obese Zucker rats (OZ), a model of morbid obesity, that insulin resistance impairs functional vasodilation via an increased thromboxane receptor (TP)-mediated vasoconstriction. Chronic treadmill exercise training improves functional vasodilation in the spinotrapezius muscle of the OZ, but the mechanisms responsible for the improvement in functional vasodilation are not clear. Based on evidence that exercise training improves insulin resistance, we hypothesized that, in the OZ, exercise training increases functional vasodilation and exercise capability due to decreases TP-mediated vasoconstriction associated with improved insulin sensitivity. Six-week-old lean Zucker rats (LZ) and OZ were exercised on a treadmill (24 m/min, 30 min/day, 5 days/wk) for 6 wk. An oral glucose tolerance test was performed at the end of the training period. We measured functional vasodilation in both exercise trained (spinotrapezius) and nonexercise trained (cremaster) muscles to determine whether the improved functional vasodilation following exercise training in OZ is due to a systemic improved insulin resistance. Compared with LZ, the sedentary OZ exhibited impairments in glucose tolerance and functional vasodilation in both muscles. The TP antagonist SQ-29548 improved the vasodilator responses in the sedentary OZ with no effect in the LZ. Exercising training of the LZ increased the functional vasodilation in spinotrapezius muscle, with no effect in the cremaster muscle. Exercising training of the OZ improved glucose tolerance, along with increased functional vasodilation, in both the spinotrapezius and cremaster muscles. SQ-29548 treatment had no effect on the vasodilator responses in either cremaster or spinotrapezius muscles of the exercise-trained OZ. These results suggest that, in the OZ, there is a global effect of exercising training to improve insulin resistance and increase functional vasodilation via a decreased TP-mediated vasoconstriction.

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