Toxicologic and pharmacologic evaluation of phleomycin including special studies on its nephrotoxicity

Rakieten, Nathan; Nadkarni, Moreshwar V.; Rakieten, Morris L.; Gordon, Benjamin S.

doi:10.1016/0041-008x(69)90018-0

Cited by 39 publications

(35 citation statements)

References 8 publications

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“…To address these questions, we first studied the expressions of AdipoR1 and -R2 during fasting and refeeding. We also analyzed the expressions of AdipoR1/R2 in an insulin deficiency model by streptozotocin (STZ) treatment (18). Moreover, we studied these expressions in a hyperinsulinemia model because of obesity-linked insulin resistance.…”

mentioning

confidence: 99%

Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity

Tsuchida

Yamauchi

Ito

et al. 2004

Journal of Biological Chemistry

487

415

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Adiponectin/Acrp30 is a hormone secreted by adipocytes, which acts as an antidiabetic and antiatherogenic adipokine. We reported previously that AdipoR1 and -R2 serve as receptors for adiponectin and mediate increased fatty acid oxidation and glucose uptake by adiponectin. In the present study, we examined the expression levels and roles of AdipoR1/R2 in several physiological and pathophysiological states such as fasting/refeeding, obesity, and insulin resistance. Here we show that the expression of AdipoR1/R2 in insulin target organs, such as skeletal muscle and liver, is significantly increased in fasted mice and decreased in refed mice. Insulin deficiency induced by streptozotocin increased and insulin replenishment reduced the expression of AdipoR1/R2 in vivo. Thus, the expression of AdipoR1/R2 appears to be inversely correlated with plasma insulin levels in vivo. Interestingly, the incubation of hepatocytes or myocytes with insulin reduced the expression of AdipoR1/R2 via the phosphoinositide 3-kinase/Foxo1-dependent pathway in vitro. Moreover, the expressions of AdipoR1/R2 in ob/ob mice were significantly decreased in skeletal muscle and adipose tissue, which was correlated with decreased adiponectin binding to membrane fractions of skeletal muscle and decreased AMP kinase activation by adiponectin. This adiponectin resistance in turn may play a role in worsening insulin resistance in ob/ob mice. In conclusion, the expression of AdipoR1/R2 appears to be inversely regulated by insulin in physiological and pathophysiological states such as fasting/refeeding, insulin deficiency, and hyperinsulinemia models via the insulin/phosphoinositide 3-kinase/Foxo1 pathway and is correlated with adiponectin sensitivity.Adiponectin/Acrp30 (1-4) is a hormone secreted by adipocytes, which acts as an antidiabetic (5-12) and antiatherogenic (8, 12, 13) adipokine. This insulin-sensitizing effect of adiponectin appears to be mediated by an increase in fatty acid oxidation via activation of the 5Ј-AMP-activated protein kinase (AMPK) 1 (10, 11) and peroxisome proliferator-activated receptor-␣ (5, 6, 12). Very recently, we have reported the cloning of complementary DNAs encoding adiponectin receptors AdipoR1 and -R2 by expression cloning (14). AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. AdipoR1 and -R2 are predicted to contain seven transmembrane domains (14) but to be structurally and functionally distinct from G-protein-coupled receptors (15-17). AdipoR1 and -R2 serve as receptors for globular and full-length adiponectin and mediate increased AMPK (10, 11), peroxisome proliferator-activated receptor-␣ ligand activities (12), and fatty acid oxidation and glucose uptake by adiponectin (14).It has not yet been determined whether the expressions of AdipoR1 and -R2 are altered in physiological and pathophysiological states. To address these questions, we first studied the expressions of AdipoR1 and -R2 during fasting and refeeding. We also analyzed the expressions of Ad...

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mentioning

confidence: 99%

Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity

Tsuchida

Yamauchi

Ito

et al. 2004

Journal of Biological Chemistry

487

415

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“…STZ has been used as a diabetogenic agent in rats and other animals. 18,19 STZ causes DNA strand breaks in pancreatic islets and stimulates nuclear poly (ADP-ribose) synthetase, and thus depletes the intracellular NAD and NADP levels. NAD depletion by STZ inhibits proinsulin synthesis and thus induces diabetes.…”

Section: Discussionmentioning

confidence: 99%

Acetone Concentration in Gas Emanating from Tails of Diabetic Rats

et al. 2012

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“…The most commonly used drug for this induction is Streptozotocin (STZ) because of its toxic effects on islet beta cells (Fadillioglu et al, 2008). (Rakieten et al, 1963; Ar'Rajab and Ahrén 1993; Gu et al, 1997). Co-morbid diseases with hyperglycaemia include high cholesterol, loss of body weight, loss of appetite etc.…”

Section: Issn: 2320-5407mentioning

confidence: 99%

Hypoglycaemic and Hypolipidemic Effects of Polyherbal Formulation in Streptozotocin-Induced Diabetic Rats.

Oyindamola¹,

Nduka²,

Banji³

et al. 2017

IJAR

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This study evaluated the effects of a polyherbal formula on the plasma lipid profile and blood glucose in Streptozotocin-induced diabetic rats. A single dose of Streptozotocin (STZ), (60 mg/kg body weight) in sodium citrate buffer at pH 4.5 was used to induce diabetes intraperitoneally in 20 adult Albino Wistar Strain Rats. 25 rats were put into 5 groups: Normal, Standard, Control, Test I and Test II respectively and were sacrificed after 7days of treatment. The weight and glucose baseline were taken prior to: (1) STZ administration (2) after a week of inducing diabetes (3) after the first, third and fifth day of treatment and (4) at sacrificial time. The body weight and blood glucose level of all animals in different groups varied depending on treatment. Blood glucose test showed that there was a significant increase in blood glucose level after induction. After treatment, the normal group blood glucose level increased by 19.12 % but not diabetic, and a decrease of 10.61 %, 61.64 %, 48.19 % and 77.16 % for the Control, Standard, Test I and Test II respectively. The body weight for normal group increased by 6.29 % while the Control group, Standard group, Test I and Test II emaciated by 7.91 %, 3.35 %, 6.9 % and 5.1 % respectively. The lipid profile test showed that Test I and Test II groups have lower lipid values compare with other study groups. Results from this study clearly indicated that the polyherbal formula had hypoglycaemic and hypolipidemic effects on Streptozotocin-induced diabetic rats.

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Toxicologic and pharmacologic evaluation of phleomycin including special studies on its nephrotoxicity

Cited by 39 publications

References 8 publications

Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity

Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity

Acetone Concentration in Gas Emanating from Tails of Diabetic Rats

Hypoglycaemic and Hypolipidemic Effects of Polyherbal Formulation in Streptozotocin-Induced Diabetic Rats.

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