Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats

Corsetti, James P.; Sparks, Janet D.; Peterson, Richard G.; Smith, Robert L.; Sparks, Charles E.

doi:10.1016/s0021-9150(99)00265-8

Cited by 154 publications

(152 citation statements)

References 43 publications

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“…2B and C). Taken together, this confirms previous reports on a sex-different development of T2D in this animal model (Clark et al 1983, Corsetti et al 2000, and suggests that 5 weeks of high-fat feeding in fZDF leads to a prediabetic state with enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and reduced glucose tolerance. Reduced insulin levels in 13-weekold mZDF have been described before (Orci et al 1990) and is indicative of diabetes development in the males.…”

Section: Resultssupporting

confidence: 92%

“…Discussion mZDF rats spontaneously develop insulin resistance, hyperglycaemia and diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (Corsetti et al 2000). This indicates that fZDF rats are protected against T2D development and that this protection is diminished in females fed this diet.…”

Section: Resultsmentioning

confidence: 91%

“…The obese Zucker diabetic fatty (ZDF/Gmi-fa) male rat has become a widely used animal model of type 2 diabetes (T2D), in contrast to the obese ZDF female that rarely develop the disease (Clark et al 1983). The males spontaneously develop insulin resistance and hyperglycaemia by 8 weeks and diabetes by 12 weeks of age, whereas the females only become diabetic when fed a diabetogenic high-fat diet (Corsetti et al 2000). Furthermore, a significant difference between males and females developing diabetes as a function of dietary fat content is accompanied by a difference in triglyceride/apolipoprotein B ratios (Corsetti et al 2000), with females secreting more triglyceride-enriched lipoprotein particles.…”

Section: Introductionmentioning

confidence: 99%

“…The males spontaneously develop insulin resistance and hyperglycaemia by 8 weeks and diabetes by 12 weeks of age, whereas the females only become diabetic when fed a diabetogenic high-fat diet (Corsetti et al 2000). Furthermore, a significant difference between males and females developing diabetes as a function of dietary fat content is accompanied by a difference in triglyceride/apolipoprotein B ratios (Corsetti et al 2000), with females secreting more triglyceride-enriched lipoprotein particles. This is in line with results obtained in healthy Sprague-Dawley (SD) rats, with females expressing higher levels of lipogenic genes in their livers (Gustavsson et al 2010) as well as having a greater capacity for hepatic uptake of long-chain fatty acids (FAs), synthesis of triglycerides and assembly of very-low-density lipoprotein (VLDL) particles (SolerArgilaga et al 1975, Soler-Argilaga & Heimberg 1976, Kushlan et al 1981.…”

Section: Introductionmentioning

confidence: 99%

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Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

Gustavsson

Soga²,

Wahlström

et al. 2011

Journal of Molecular Endocrinology

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Male Zucker diabetic fatty (mZDF) rats spontaneously develop type 2 diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (high-fat-fed female ZDF rat, HF-fZDF). The aim of this study was to investigate if differences in liver functions could provide clues to this sex difference. Non-diabetic obese fZDF rats were compared with either mZDF or HF-fZDF regarding hepatic molecular profiles, to single out those components that might be protective in the females. High-fat feeding in fZDF led to enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and a trend towards reduced glucose tolerance, indicative of a prediabetic state. mZDF rats were diabetic, with low levels of insulin, high levels of glucose, reduced insulin sensitivity and impaired glucose tolerance. Transcript profiling and capillary electrophoresis time-of-flight mass spectrometry were used to indentify hepatic transcripts and metabolites that might be related to this. Many diet-induced alterations in transcript and metabolite levels in female rats were towards a 'male-like' phenotype, including reduced lipogenesis, increased fatty acid (FA) oxidation and increased oxidative stress responses. Alterations detected at the level of hepatic metabolites, indicated lower capacity for glutathione (GSH) production in male rats, and higher GSH turnover in females. Taken together, this could be interpreted as if anabolic pathways involving lipogenesis and lipid output might limit the degree of FA oxidation and oxidative stress in female rats. Together with a greater capacity to produce GSH, these hepatic sex differences might contribute to the sex-different development of diabetes in ZDF rats.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

Gustavsson

Soga²,

Wahlström

et al. 2011

Journal of Molecular Endocrinology

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“…Zucker diabetic fatty (ZDF) rat is an excellent model of T2DM because it shows characteristics similar to T2DM in humans [8,30,38]. Overt T2DM in ZDF rats consists of severe hyperglycemia, polydipsia, and attenuated body weight gain [31,41].…”

mentioning

confidence: 99%

Differential Effects of Treadmill Exercise on Calretinin Immunoreactivity in Type 2 Diabetic Rats in Early and Chronic Diabetic Stages

Nam

Hwang

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. In this study, we investigated the effects of treadmill exercise on calretinin (CR), a marker of early postmitotic neurons, immunoreactivity in the dentate gyrus (DG) of Zucker diabetic fatty (ZDF) rats, before or after diabetes onset, and Zucker lean control (ZLC) rats. For this study, 6-week-old ZLC and prediabetic ZDF rats, and 22-week-old ZLC and ZDF rats were exercised on the treadmill. Sedentary ZLC and ZDF rats of the same age were used as exercise experiment controls. The exercised prediabetic ZDF rats did not show diabetes onset, while the sedentary prediabetic ZDF rats showed significantly increased blood glucose levels. The exercised diabetic ZDF rats exhibited a decrease in their blood glucose levels compared to the sedentary diabetic ZDF rats, but the levels were still above 20 mmol/l. ZLC rats of both ages were in the normoglycemic range. CR immunoreactivity was detected throughout the DG, including the subgranular zone and the polymorphic layer. Diabetic rats exhibited a significant decrease in the number of CR-immunoreactive cells and fibers in the DG. Exercise in the prediabetic ZDF rats significantly increased the number of CR-immunoreactive cells and fibers in the subgranular zone of the DG. In the ZLC and ZDF rats of chronic diabetic phase, exercise increased CR-immunoreactive neurons in the hilar region. These results suggest that diabetes significantly reduces the number of postmitotic CR-immunoreactive neurons and the intensity of immunoreactivity and that exercise increases these CR-related parameters in a diabetic stagedependent manner.

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Bridging Bench to Clinic: Roles of Animal Models for Post‐Genomics Drug Discovery on Metabolic Diseases

Wong

Chen

2006

Drug Discovery Research

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Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats

Cited by 154 publications

References 43 publications

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

Differential Effects of Treadmill Exercise on Calretinin Immunoreactivity in Type 2 Diabetic Rats in Early and Chronic Diabetic Stages

Bridging Bench to Clinic: Roles of Animal Models for Post‐Genomics Drug Discovery on Metabolic Diseases

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