Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats

Fujiwara, Toshihiko; Yoshioka, Shinji; Yoshioka, T.; Ushiyama, I.; Horikoshi, Hiroyoshi

doi:10.2337/diabetes.37.11.1549

Cited by 237 publications

(140 citation statements)

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“…The TGZ dose used in this study is equivalent to 130–140 mg/kg and has been frequently used in rat pharmacologic studies [4, 9, 17]. Treatment using TGZ in fa/fa rats reduced plasma TG and T-Chol levels in the present study; these plasma-lipid effects are consistent with previously reported data from both human and animal experiments [11, 18].…”

Section: Discussionsupporting

confidence: 90%

“…TGZ is a prototype thiazolidinedione derivative that is reported to improve insulin resistance through its action on peroxisome proliferator-activated receptor gamma (PPARγ) [4]. Previous studies have suggested that TGZ promotes the apoptosis of hypertrophic/large adipocytes and the differentiation of preadipocytes into small adipocytes [6, 13, 19].…”

Section: Discussionmentioning

confidence: 99%

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Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-Leprfa Rats

Okuno

Kaji

Takahashi

et al. 2013

The Journal of Veterinary Medical Science

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WBN/Kob-Leprfa (fa/fa) rats have been identified as a new animal model of type 2 diabetes (T2DM), as they are characterized by impaired pancreatic insulin secretion and severe insulin resistance. Our previous study demonstrated impaired insulin secretion and its involvement in hyperglycemia in fa/fa rats. The present study was aimed at elucidating the role of insulin resistance in the development and progression of diabetes in these animals. Troglitazone (TGZ) was used as an insulin sensitizer. Insulin resistance and insulin secretory capacity were measured by a homeostasis model assessment of insulin resistance and the area under the blood concentration–time curve for plasma insulin levels after intravenous glucose tolerance testing, respectively. The fa/fa rats exhibited marked insulin resistance between 5 and 11 weeks of age, compared with age-matched Wistar rats. The insulin secretory capacity of fa/fa rats was higher than that of Wistar rats at 5 weeks of age, but decreased by 50% between 9 and 11 weeks of age. The fa/fa rats were fed a standard diet, with or without 0.2% w/w TGZ, for 4 weeks. Treatment with TGZ significantly improved insulin resistance, hyperglycemia and hypertriglyceridemia in both prophylactic and therapeutic study groups. These results suggest that insulin resistance is markedly involved in the development and progression of T2DM in fa/fa rats.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-Leprfa Rats

Okuno

Kaji

Takahashi

et al. 2013

The Journal of Veterinary Medical Science

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“…Thiazolidinediones are high-affinity ligands for PPAR-γ [74] and have strong insulin-sensitising effects [75]. They enhance the expression of adiponectin mRNA within adipocytes [52] and increase the plasma concentration of adiponectin, with a specific increase in the HMW component [76].…”

Section: Adiponectin In Critical Illnessmentioning

confidence: 99%

Clinical review: Adiponectin biology and its role in inflammation and critical illness

2011

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Adiponectin is an adipokine first described just over a decade ago. Produced almost exclusively by adipocytes, adiponectin circulates in high concentrations in human plasma. Research into this hormone has revealed it to have insulin-sensitizing, anti-inflammatory and cardioprotective roles. This review discusses the history, biology and physiological role of adiponectin and explores its role in disease, with specific focus on adiponectin in inflammation and sepsis. It appears that an inverse relationship exists between adiponectin and inflammatory cytokines. Low levels of adiponectin have been found in critically ill patients, although data are limited in human subjects at this stage. The role of adiponectin in systemic inflammation and critical illness is not well defined. Early data suggest that plasma levels of adiponectin are decreased in critical illness. Whether this is a result of the disease process itself or whether patients with lower levels of this hormone are more susceptible to developing a critical illness is not known. This observation of lower adiponectin levels then raises the possibility of therapeutic options to increase circulating adiponectin levels. The various options for modulation of serum adiponectin (recombinant adiponectin, thiazolidinediones) are discussed.

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“…2 The thiazolidinediones are a class of compounds that reduce insulin resistance in animals with hyperglycemia and hyperinsulinemia. [4][5][6][7][8] These drugs have antihyperglycemic effects only in the presence of insulin 9 and do not cause hypoglycemia in nondiabetic animals. 9,10 In humans, administration of the thiazolidinedione troglitazone increased insulin-stimulated glucose disposal in obese subjects and patients with type II diabetes, demonstrating its ability to ameliorate insulin resistance.…”

mentioning

confidence: 99%

Effect of Troglitazone in Insulin-Treated Patients with Type II Diabetes Mellitus

et al. 1998

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Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats

Cited by 237 publications

References 0 publications

Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-<i>Lepr<sup>fa</sup></i> Rats

Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-<i>Lepr<sup>fa</sup></i> Rats

Clinical review: Adiponectin biology and its role in inflammation and critical illness

Effect of Troglitazone in Insulin-Treated Patients with Type II Diabetes Mellitus

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