Effect of troglitazone (CS-045) and bezafibrate on glucose tolerance, Liver Glycogen synthase activity, and β-oxidation in fructose-fed rats

Inoue, Ituro; Takahashi, Keiichi; Katayama, Shigehiro; Harada, Yumi; Negishi, Kiyohiko; Itabashi, Akira; Ishii, Jun

doi:10.1016/0026-0495(95)90085-3

Cited by 48 publications

(29 citation statements)

References 22 publications

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“…In contrast to insulin, troglitazone-induced glucose transport was accompanied by distinct inhibition of glycogen synthesis and marked stimulation of glycolysis resulting in a reduction of glycogen stores. Troglitazone stimulation of glycogen synthase activity observed in other experimental setups (Ciaraldi et al, 1990;Inoue et al, 1995) has not been substantiated in this study. Thus, acute troglitazone exposure exerts non-insulin-like and non-insulin-sensitizing actions on intracellular routing of glucosyl units and, hence, beyond glucose transport resembles the catabolic e ects of hypoxia (FuÈ rnsinn et al, 1996).…”

Section: Discussioncontrasting

confidence: 81%

Acute non‐insulin‐like stimulation of rat muscle glucose metabolism by troglitazone in vitro

Fürnsinn

Neschen

Noe

et al. 1997

British J Pharmacology

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1 The direct short-term e ects of troglitazone on parameters of glucose metabolism were investigated in rat soleus muscle strips. 2 In muscle strips from Sprague-Dawley rats, troglitazone (3.25 mmol l 71 ) increased basal and insulinstimulated glucose transport by 24% and 41%, respectively (P50.01 each). 3 In the presence of 5 nmol l 71 insulin, stimulation of glucose transport by 3.25 mmol l 71 troglitazone was accompanied by a 36% decrease in glycogen synthesis, while glycolysis was increased (112% increase in lactate production) suggesting a catabolic response of intracellular glucose handling. 4 Whereas insulin retained its stimulant e ect on [ 3 H]-2-deoxy-glucose transport in hypoxia-stimulated muscle (by 44%; c.p.m. mg 71 h 71 : 852+77 vs 1229+75, P50.01), 3.25 mmol l 71 troglitazone failed to increase glucose transport under hypoxic conditions (789+40 vs 815+28, NS) suggesting that hypoxia and troglitazone address a similar, non-insulin-like mechanism. 5 No di erences between troglitazone and hypoxia were identi®ed in respective interactions with insulin. 6 Troglitazone acutely stimulated muscle glucose metabolism in a hypoxia/contraction-like manner, but it remains to be elucidated whether this contributes to the long-term antidiabetic and insulin enhancing potential in vivo or is to be regarded as an independent pharmacological e ect.

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Section: Discussioncontrasting

confidence: 81%

Acute non‐insulin‐like stimulation of rat muscle glucose metabolism by troglitazone in vitro

Fürnsinn

Neschen

Noe

et al. 1997

British J Pharmacology

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“…Unfortunately, neither of these metabolites was measured in the present study, although a reduction of both in response to troglitazone treatment has been consistently documented in animal and human studies (17)(18)(19). The effects of free fatty acids on insulin secretion are complex (52,53).…”

Section: Discussionmentioning

confidence: 63%

“…It has been demonstrated previously that a number of therapeutic interventions can improve glucose tolerance in subjects with IGT, including weight loss (10,11), treatment with sulfonylureas (11,12), the biguanide drug metformin (13,14), and more recently the thiazolidinediones (15)(16)(17). Thiazolidinediones have been proposed to act primarily as insulin sensitizers since they improve hepatic and peripheral insulin resistance and lower triglycerides and free fatty acids (15,(17)(18)(19)(20). Although the thiazolidinediones do not appear to be insulin secretagogues (21), we have observed in the Zucker diabetic fatty rat, an animal model of non-insulin-dependent diabetes mellitus (NIDDM), that if administered before the onset of diabetes, these drugs can prevent the deterioration in ␤ cell function that is associated with overt disease (22,23).…”

Section: Impaired Glucose Tolerance (Igt)mentioning

confidence: 99%

Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance.

Cavaghan¹,

Ehrmann²,

Byrne³

et al. 1997

J. Clin. Invest.

195

128

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Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of ␤ cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone ( n ϭ 14) or placebo ( n ϭ 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (S I ) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and ␤ cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% ( P ϭ 0.03) and 39% ( P ϭ 0.003), respectively. S I increased from 1.3 Ϯ 0.3 to 2.6 Ϯ 0.4 ϫ 10 Ϫ 5 min Ϫ 1 pM Ϫ 1 ( P ϭ 0.005). Average insulin secretion rates adjusted for S I over the glucose interval 5-11 mmol/liter were increased by 52% ( P ϭ 0.02), and the ability of the ␤ cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% ( P ϭ 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced ␤ cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance. ( J. Clin. Invest. 1997. 100: 530-537.)

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“…Recently, Inoue et al [35] showed a decrease in liver mitochondrial palmitic j3-oxidation rate by troglitazone in fructose-fed rats. In this study, muscle 3-HADH activity, an enzyme in jS-oxidation, was almost identical in all groups, suggesting that troglitazone may not affect j3-oxidation in muscle, contrary to that in the liver as previously reported [7,35]. There was also no effect of troglitazone treatment on fasting insulin concentrations.…”

Section: Discussionmentioning

confidence: 98%

“…Troglitazone is also reported to reduce hepatic triglyceride production and enhance the rate of triglyceride removal [7]. Recently, Inoue et al [35] showed a decrease in liver mitochondrial palmitic j3-oxidation rate by troglitazone in fructose-fed rats. In this study, muscle 3-HADH activity, an enzyme in jS-oxidation, was almost identical in all groups, suggesting that troglitazone may not affect j3-oxidation in muscle, contrary to that in the liver as previously reported [7,35].…”

Section: Discussionmentioning

confidence: 99%

Troglitazone Improves Insulin-Stimulated Glucose Utilization Associated with an Increased Muscle Glycogen Content in Obese Zucker Rats.

et al. 1999

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Effect of troglitazone (CS-045) and bezafibrate on glucose tolerance, Liver Glycogen synthase activity, and β-oxidation in fructose-fed rats

Cited by 48 publications

References 22 publications

Acute non‐insulin‐like stimulation of rat muscle glucose metabolism by troglitazone in vitro

Acute non‐insulin‐like stimulation of rat muscle glucose metabolism by troglitazone in vitro

Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance.

Troglitazone Improves Insulin-Stimulated Glucose Utilization Associated with an Increased Muscle Glycogen Content in Obese Zucker Rats.

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