Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus

Kawamori, Ryuzo; Matsuhisa, Munehide; Kinoshita, Junichiro; Mochizuki, Kentaro; Niwa, Masataka; Arisaka, Tomoyuki; Ikeda, Masahiko; Kubota, Minoru; Wada, Masahiko; Kanda, Tsutomu; Ikebuchi, Motoyoshi; Tohdo, Ryohei; Yamasaki, Yoshimitsu

doi:10.1016/s0168-8227(98)00056-4

Cited by 60 publications

(42 citation statements)

References 21 publications

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“…These findings are in concordance with recent publications (35,36) in which a 12-77% improvement of the glucose infusion rate and an ϳ30% improvement of the insulinstimulated diaphragm or splanchnic glucose uptake rate have been reported. Since the steady-state insulin concentrations were lower during the second than first clamp examinations in both the metformin and the rosiglitazone groups, we may have actually underestimated the effect of treatment on whole-body insulin sensitivity.…”

supporting

confidence: 93%

Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects

et al. 2003

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We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n ‫؍‬ 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[18 F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ؎ 2.0 to 23.0 ؎ 2.6 mol ⅐ kg ؊1 ⅐ min

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supporting

confidence: 93%

Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects

et al. 2003

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“…Bezafibrates substantially reduced the hepatic steatosis in ArKO males (Toda et al 2001b, Yoshikawa et al 2002, and improved glucose tolerance during IPGTT and insulin sensitivity during ITT. Pioglitazone, a thiazolidinedione, interacts with PPAR to enhance the actions of insulin with resulting improvement in insulin-dependent glucose disposal and reduction in hepatic glucose output (Lehmann et al 1995, Kawamori et al 1998. Treatment with pioglitazone also improved the abnormality in carbohydrate metabolism in ArKO males and restored the insulin sensitivity in ITT.…”

Section: Discussionmentioning

confidence: 99%

Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency

Takeda

Toda²,

Saibara³

et al. 2003

Journal of Endocrinology

165

121

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Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO ( / ) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26·7 1·9 g vs 26·1 0·8 g and 28·8 1·4 g vs 26·9 1·0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P<0·05). The ArKO males showed significantly higher blood glucose levels during an intraperitoneal glucose tolerance test compared with wild-type littermates beginning at 18 weeks of age. By 24 weeks of age, they had higher fasting blood glucose levels compared with wild-type littermates (133·8 22·8 mg/dl vs 87·8 20·3 mg/dl respectively; P<0·01). An intraperitoneal injection of insulin (0·75 mU insulin/g) caused a continuous decline in blood glucose levels in wild-type mice whereas ArKO males at 18 weeks and older exhibited a rebound increase in glucose levels 30 min after insulin injection. Thus, ArKO male mice appear to develop glucose intolerance and insulin resistance in an age-dependent manner. There was no difference in fasting serum triglyceride and total cholesterol levels between ArKO male mice and wild-type littermates at 13 and 25 weeks of age. However, serum triglyceride and cholesterol levels were significantly elevated following a meal in ArKO mice at 36 weeks of age. Serum testosterone levels in ArKO male mice were continuously higher compared with wild-type littermates. Treatment of ArKO males with 17 -estradiol improved the glucose response as measured by intraperitoneal glucose and insulin tolerance tests. Treatment with fibrates and thiazolidinediones also led to an improvement in insulin resistance and reduced androgen levels. As complete aromatase deficiency in man is associated with insulin resistance, obesity and hyperlipidemia, the ArKO mouse may be a useful animal model for examining the role of estrogens in the control of glucose and lipid homeostasis.

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“…Moreover, in contrast to the insulin clamp, the whole-body ISI during OGTT is greatly influenced by 1) glucose-mediated glucose uptake and the combined effects of hyperinsulinemia plus hyperglycemia to augment glucose disposal, 2) less effective suppression of hepatic glucose production (21), and 3) splanchnic uptake of 30 -40% of the ingested glucose load (21). With regard to the latter, Kawamori et al (22) have suggested that pioglitazone augments splanchnic glucose uptake after glucose ingestion. These considerations suggest that mechanisms, in addition to improved insulin sensitivity in muscle, contribute to the improvement in whole-body insulin sensitivity during OGTT after pioglitazone therapy.…”

Section: Correlation Analysesmentioning

confidence: 99%

Dose-Response Effect of Pioglitazone on Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes

2002

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OBJECTIVE -To investigate the dose-response effects of pioglitazone on glycemic control, insulin sensitivity, and insulin secretion in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 58 diet-treated patients with type 2 diabetes (aged 54 Ϯ 1 years; 34 men and 24 women; BMI 31.5 Ϯ 0.6 kg/m 2 ) were randomly assigned to receive placebo (n ϭ 11) or 7.5 mg (n ϭ 13), 15 mg (n ϭ 12), 30 mg (n ϭ 11), or 45 mg (n ϭ 11) of pioglitazone per day for 26 weeks. Before and after 26 weeks, subjects underwent a 75-g oral glucose tolerance test (OGTT). RESULTS

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Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus

Cited by 60 publications

References 21 publications

Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects

Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects

Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency

Dose-Response Effect of Pioglitazone on Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes

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