Characterization of STZ-Induced Type 2 Diabetes in Zucker Fatty Rats

Okamoto, Takashi; Kanemoto, Naohide; Ohbuchi, Yutaka; Okano, M.; Fukui, Hirokazu; Sudo, Toshiki

doi:10.1538/expanim.57.335

Cited by 20 publications

(13 citation statements)

References 27 publications

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“…It has been reported that metformin has multiple activities, including suppression of hepatic glucose, production and improvement of peripheral insulin sensitivity, in type 2 diabetic patients. So, it reduces hyperglycemia (Tang and Reed, 2001;Saravanan and Pari, 2006;Okamoto et al, 2008;Anurag and Anuradha, 2002). In the present study, we observed that metformin rapidly decreased blood glucose levels.…”

Section: Discussionsupporting

confidence: 65%

The effect of metformin and exercise on serum lipids, nitric oxide synthase and liver nitric oxide levels in streptozotocin-nicotinamide induced diabetic rats

Akyüz¹,

Tekin²,

Aydn³

et al. 2012

Afr. J. Pharm. Pharmacol.

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The objective of this study was to determine the effects of metformin treatment and exercise intervention on lipid metabolism, nitric oxide (NO), nitric oxide synthase (NOS) and glucose levels in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats. Male wistar rats were used to conduct the study and they were divided into five groups of 8 rats in each. These groups are: Control group, diabetes group (STZ-NA), diabetes and metformin (DMet) group, diabetes and exercise (DE) group, and diabetes + exercise + metformin (DEMet) group. The STZ-NA induced diabetic rats were used as a model of type 2 diabetes. Metformin was orally administered to rats. For exercise intervention, rats were forced to run in a running wheel for 10 min each day (20 m/min/day). At the end of experimental period, blood glucose, glycated hemoglobin (HbA1c) levels, plasma lecithin:cholesterol acyltransferase (LCAT) levels, serum triglyceride (TG), cholesterol, high density lipoprotein (HDL), Apo A-I, NOS and liver NO levels were determined. Metformin caused beneficial changes in blood glucose, HbA1c levels, and HDL in type 2 diabetic rats. Both administration of metformin and exercise intervention independently caused beneficial changes in blood glucose. However, the surprising result found was that exercise intervention did not optimize the result of metformin treatment. The other finding of this study was that exercise intervention increased cholesterol and NOS level but exercise combined with metformin was not better than exercise alone. Thus, it appears from the present study that metformin and exercise combination has no effect.

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Section: Discussionsupporting

confidence: 65%

The effect of metformin and exercise on serum lipids, nitric oxide synthase and liver nitric oxide levels in streptozotocin-nicotinamide induced diabetic rats

Akyüz¹,

Tekin²,

Aydn³

et al. 2012

Afr. J. Pharm. Pharmacol.

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“…In the present study we used the obese diabetic animal model of B6 mouse fed HFD. Okamoto et al 19) reported that a single oral administration of metformin at 300 mg/kg reduced blood glucose levels of streptozotocin (30 mg/kg i.p. )-induced type 2 diabetes in Zucker fatty rats.…”

Section: Discussionmentioning

confidence: 99%

Metformin Reduces Body Weight Gain and Improves Glucose Intolerance in High-Fat Diet-Fed C57BL/6J Mice

Matsui

Hirasawa²,

Sugiura³

et al. 2010

Biological & Pharmaceutical Bulletin

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In developed countries including Japan, in recent years, the incidence of obesity has sharply increased by the overintake of calorie-rich diet and exercise-lacking lifestyles. 1)Metabolic syndrome caused by obesity with abdominal adiposity especially is a strong risk factor for type 2 diabetes 2) and cardiovascular diseases.3) Obesity in humans generally involves the interaction of multiple genes and environmental factors.Pioglitazone, a thiazolidinedione that improves insulin resistance, has been widely used for the treatment of type 2 diabetes with obesity and insulin resistance. However, body weight gain is frequently observed in patients during the administration of pioglitazone. 4)On the other hand, metformin, a biguanide that improves insulin resistance similarly to pioglitazone, has been also widely used for the treatment of type 2 diabetes. It has been reported that obese patients with type 2 diabetes treated with metformin do not gain body weight; indeed many patients on this agent lose body weight by decreasing food consumption.5-8) However, the mechanisms by which metformin treatment causes reduction of food consumption and body weight loss are not fully clarified. It has been indicated that metformin increases plasma active glucagon-like peptide-1 (GLP-1) in obese nondiabetic subjects.9) GLP-1 is an incretin released from L cells in the intestine after oral ingestion of nutrients. This incretin has several actions such as stimulation of insulin biosynthesis, inhibition of glucagon secretion, and inhibition of gastric emptying in addition to promotion of satiety and inhibition of food intake. 10)Both metformin and pioglitazone are currently used as first-choice agents for the treatment for type 2 diabetes with obesity in Japan, even though they have opposite effects against body weight. Therefore it may be useful to clarify the differences in the effects of metformin and pioglitazone for prevention and treatment of obese type 2 diabetes and cardiovascular diseases produced as the result of development of metabolic syndrome. To investigate the effects of metformin on food intake and body weight gain, genetically obese diabetic mice such as db/db 11) or rats such as fa/fa, 12) GotoKakizaki (GK), 13) Otsuka Long-Evans Tokusima Fatty (OLETF), 14) and Zucker 15) have been generally used. However, daily oral administration of metformin to these genetically obese diabetic animals does not strongly affect body weight gain. On the other hand, we have recognized that daily treatment with pioglitazone given as food mixture (0.01, 0.02%) causes marked increases in food intake and body weight, although treatment with this drug removed hyperglycemia and hyperlipidemia. 16) Dietary fats are considered one of the most important environmental factors in the pathophysiology of obesity, and dietary fats-induced obesity is strongly related to lifestyle. However, it is unknown whether metformin causes body weight loss, while pioglitazone causes body weight gain, when administered to animals with high-fat diet-induced obes...

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“…The serum leptin level of db/db mice is much higher and quite variable, ranging from ~100 ng/ml in 4-week-old mice [171] to ~4000 ng/ml in 6-week-old mice [172]. Marked variability has also been shown in rats: Zucker fatty rats have shown serum leptin levels ranging from 0.15 ng/ml [173] to 10-50 ng/ml [174] up to 700 ng/ml [175] at overlapping ages. Serum leptin levels of male ZDF rats are 20-40 ng/ml and variable at ages 10-36 weeks [176-178].…”

Section: Introductionmentioning

confidence: 99%

Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes

Wang¹,

Chandrasekera

Pippin

2014

CDR

433

348

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Among the most widely used animal models in obesity-induced type 2 diabetes mellitus (T2DM) research are the congenital leptin- and leptin receptor-deficient rodent models. These include the leptin-deficient ob/ob mice and the leptin receptor-deficient db/db mice, Zucker fatty rats, Zucker diabetic fatty rats, SHR/N-cp rats, and JCR:LA-cp rats. After decades of mechanistic and therapeutic research schemes with these animal models, many species differences have been uncovered, but researchers continue to overlook these differences, leading to untranslatable research. The purpose of this review is to analyze and comprehensively recapitulate the most common leptin/leptin receptor-based animal models with respect to their relevance and translatability to human T2DM. Our analysis revealed that, although these rodents develop obesity due to hyperphagia caused by abnormal leptin/leptin receptor signaling with the subsequent appearance of T2DM-like manifestations, these are in fact secondary to genetic mutations that do not reflect disease etiology in humans, for whom leptin or leptin receptor deficiency is not an important contributor to T2DM. A detailed comparison of the roles of genetic susceptibility, obesity, hyperglycemia, hyperinsulinemia, insulin resistance, and diabetic complications as well as leptin expression, signaling, and other factors that confound translation are presented here. There are substantial differences between these animal models and human T2DM that limit reliable, reproducible, and translatable insight into human T2DM. Therefore, it is imperative that researchers recognize and acknowledge the limitations of the leptin/leptin receptor-based rodent models and invest in research methods that would be directly and reliably applicable to humans in order to advance T2DM management.

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Characterization of STZ-Induced Type 2 Diabetes in Zucker Fatty Rats

Cited by 20 publications

References 27 publications

The effect of metformin and exercise on serum lipids, nitric oxide synthase and liver nitric oxide levels in streptozotocin-nicotinamide induced diabetic rats

The effect of metformin and exercise on serum lipids, nitric oxide synthase and liver nitric oxide levels in streptozotocin-nicotinamide induced diabetic rats

Metformin Reduces Body Weight Gain and Improves Glucose Intolerance in High-Fat Diet-Fed C57BL/6J Mice

Leptin- and Leptin Receptor-Deficient Rodent Models: Relevance for Human Type 2 Diabetes

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