Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice

Kume, Eisuke; Fujimura, H.; Matsuki, Naoaki; Ito, Masahito; Aruga, Chinami; Toriumi, Wataru; Kitamura, Kazuyuki; Doi, Kunio

doi:10.1078/0940-2993-00351

Cited by 60 publications

(57 citation statements)

References 26 publications

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“…Further, robust hyperglycemic response was discernible among PP rats of both age groups, clearly suggesting extensive pancreatic b cell death after STZ treatment. Although earlier evidences indicate hypertriglyceridemia and hypercholesterolemia during overt diabetes among experimental animals, 43 we found significant reduction in serum triglyceride/cholesterol levels among PP diabetic rats, which is likely to be because of one or several interdependent factors, such as oxidative loss of membrane lipids, decreased lipid biosynthesis and/or poor nutritional status.…”

Section: Discussioncontrasting

confidence: 95%

Evidence of oxidative stress and mitochondrial dysfunctions in the testis of prepubertal diabetic rats

Chandrashekar

Muralidhara

2009

Int J Impot Res

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Earlier, we have shown the occurrence of oxidative impairments and their progression in the testis of diabetic adult rats. This study investigated the vulnerability of immature testis to oxidative stress and mitochondrial dysfunctions in a prepubertal (PP) diabetic rat model. PP male rats (4/6-weekold) rendered diabetic by an acute dose of streptozotocin were monitored for induction of oxidative stress in testis cytosol/mitochondria. Diabetic rats of both age groups showed severe hyperglycemia, testicular atrophy and marked oxidative damage as evidenced by enhanced generation of reactive oxygen species, hydroperoxide and malondialdehyde levels (4 week46 week). Mitochondrial dysfunctions manifested as reduction in the activities of aldehyde dehydrogenase, tricarboxylic acid cycle enzymes, enhanced activities of oxidative phosphorylation enzymes, perturbations in calcium homeostasis and membrane potential. These evidences suggest that an immature testis is vulnerable to oxidative stress under diabetes, which may play a significant role in the development of testicular degeneration, leading to impaired fertility in adulthood.

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Section: Discussioncontrasting

confidence: 95%

Evidence of oxidative stress and mitochondrial dysfunctions in the testis of prepubertal diabetic rats

Chandrashekar

Muralidhara

2009

Int J Impot Res

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“…STZ is often used to generate animal models of type cells (Weiss, 1982;Kume et al, 1994;Kume et al, 2004 ). Under our experimental conditions, a dose-dependent typical hyperglycemia (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…However, no change in serum ALT activity as shown in Fig. 2-D strongly indicated that 2 week-STZ treatment did not cause hepatitis with damage to hepatocellular membrane although STZ is known to exert acute hepatic changes including lipid peroxidation, mitochondrial swelling, and inhibition of hepatocyte proliferation before the elevation of the serum glucose levels (Kume et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…However, the pathophysiological roles of 3'-AMP and its forming enzyme have not yet been elucidated. Streptozotocin (STZ) is known to exert toxic effects not including liver (Weiss, 1982;Kume et al, 1994;Haluzík and Nedvídková, 2000;Kume et al, 2004 ). The liver is a major target of insulin action, and plays an important role in maintaining blood glucose levels (Dhahbi et al, 2003;Parker et al et al (1990) demonstrated that STZ-induced increase in 3'-AMP levels in rat liver could be largely reversed by insulin treatment.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic changes in adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in streptozotocin-induced diabetic mice

et al. 2008

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AMP) forming enzyme in mice, the effect of streptozotocin (STZ) on the enzyme activities and adenine nucleotide levels in the ICR mice (4-week-old) liver was examined. After 2 weeks, treatment with a single dosage of STZ (100, 150 or 200 mg/kg i.p.) induced a dose-dependent hyperglycemia and hypoinsulinemia but had no effect on serum alanine aminotransferase activity, indicating that STZ generated type 1 diabetes without hepatitis. In the diabetic liver, the activities of superoxide dismutase (SOD), catalase and ATP levels decreased, and the microsomal CYP2E1 activity increased. Changes of these biological activities might disrupt the cellular homeostatic balance of reactive oxygen species (ROS) production. The activities of 3'-AMP forming enzyme, one of the ribonucleases, in hepatic homogenates were not altered. However, in the STZ 200 mg/kg group, the cytosolic forming enzyme activities were in the mitochondrial activity may be accelerated by development of diabetes due to the decrease in the antioxidant defense system and/or increase in ROS production. With the decrease in the 3'-AMP forming enzyme activity, the levels of 3'-AMP, a P-site inhibitor of adenylate cyclase, in mitochondrial were -ment of diabetes. Our results also suggested that change in cytosolic enzyme activity might serve as a new 3'-AMP forming enzyme and SOD was found in the early stage of diabetes.

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“…By combining beta-cell-specific BLI and diphtheria receptor expression, we were able to manipulate beta-cell mass by rapid, selective, and complete beta-cell destruction (28) and noninvasively assay this alteration with BLI. Additionally, this approach avoids the pleiotropic effects of streptozotocin, a drug widely used to induce beta-cell destruction that is also toxic to several organs (31,32) and may affect radiotracer biodistribution and clearance. We used these alternative approaches and models to evaluate a family of PET radiotracers that bind VMAT2, a target predicted to be useful for noninvasive imaging of the pancreatic beta cell.…”

Section: Discussionmentioning

confidence: 99%

Multimodal image coregistration and inducible selective cell ablation to evaluate imaging ligands

Virostko

Henske

Vinet

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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We combined multimodal imaging (bioluminescence, X-ray computed tomography, and PET), tomographic reconstruction of bioluminescent sources, and two unique, complementary models to evaluate three previously synthesized PET radiotracers thought to target pancreatic beta cells. The three radiotracers {[ 18 F]fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]FP-DTBZ), [ 18 F](+)-2-oxiranyl-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinoline ( 18 F-AV-266), and (2S,3R, 11bR)-9-(3-fluoropropoxy)-2-(hydroxymethyl)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ( 18 F-AV-300)} bind vesicular monoamine transporter 2. Tomographic reconstruction of the bioluminescent signal in mice expressing luciferase only in pancreatic beta cells was used to delineate the pancreas and was coregistered with PET and X-ray computed tomography images. This strategy enabled unambiguous identification of the pancreas on PET images, permitting accurate quantification of the pancreatic PET signal. We show here that, after conditional, specific, and rapid mouse beta-cell ablation, beta-cell loss was detected by bioluminescence imaging but not by PET imaging, given that the pancreatic signal provided by three PET radiotracers was not altered. To determine whether these ligands bound human beta cells in vivo, we imaged mice transplanted with luciferase-expressing human islets. The human islets were imaged by bioluminescence but not with the PET ligands, indicating that these vesicular monoamine transporter 2-directed ligands did not specifically bind beta cells. These data demonstrate the utility of coregistered multimodal imaging as a platform for evaluation and validation of candidate ligands for imaging islets.diabetes | insulin | molecular imaging | pancreatic islet | bioluminescence tomography

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Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice

Cited by 60 publications

References 26 publications

Evidence of oxidative stress and mitochondrial dysfunctions in the testis of prepubertal diabetic rats

Evidence of oxidative stress and mitochondrial dysfunctions in the testis of prepubertal diabetic rats

Hepatic changes in adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in streptozotocin-induced diabetic mice

Multimodal image coregistration and inducible selective cell ablation to evaluate imaging ligands

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