Effect of dietary sucrose on the SHR/N-corpulent rat: a new model for insulin-independent diabetes

Michaelis, Otho E.; Ellwood, Kathleen C.; Judge, Joan M.; Schoene, Norberta W.; Hansen, Carl T.

doi:10.1093/ajcn/39.4.612

Cited by 93 publications

(58 citation statements)

References 33 publications

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“…In a recently established congenic strain of genetically obese rats (SHR/N-corpulent), blood pressure in the obese animals was found to be lower than that in the lean congenic controls. 20 Thus, in all of these genetically obese strains, increased blood pressure is not specifically associated with the obese genotype. Such strains would not seem to be suitable for investigating the pathogenetic relation between obesity and hypertension.…”

Section: *Statistically Significant Difference When Compared With Thementioning

confidence: 98%

The Zucker fatty rat as a genetic model of obesity and hypertension.

1989

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The association of hypertension with obesity has long been recognized; however, because of the lack of suitable animal models of obesity and hypertension, the pathogenesis of the high blood pressure associated with obesity remains poorly understood. We hypothesized that the Zucker fatty rat, a widely studied model of obesity and insulin resistance, might also be characterized by hypertension. Mean arterial pressure directly measured in the unanesthetized, unrestrained obese (fatty) Zucker rat was significantly greater than in two strains of nonobese control rats, the lean Zucker rat and the Lewis rat. The greater blood pressure in the obese rats was not dependent on hyperphagia or increased body weight per se since moderate caloric restriction, achieved by pair-feeding with lean rats, decreased weight gain but did not attenuate hypertension. Pair-fed obese rats retained less sodium than lean control rats, suggesting that greater blood pressure in the obese rats is not a consequence of increased renal retention of sodium. A unique feature of the Zucker strain is that the increased blood pressure appears to be specifically associated with the obese genotype. The findings suggest that the obese Zucker rat might provide a useful experimental model of obesity and hypertension. (Hypertension 1989;13:896-901) T he association of clinical hypertension (high blood pressure) with obesity is well recognized. In a recent survey in which body weight and blood pressure were measured in 1 million Americans, Stamler et al 1 found that hypertension was twice as prevalent in younger overweight subjects and 50% more prevalent in older obese individuals than in normal-weight control subjects. However, despite the well-established association between obesity and hypertension, the pathophysiological relation between obesity and hypertension remains poorly understood. Lack of information regarding the pathogenesis of the high blood pressure associated with obesity has been attributed, in part, to the lack of suitable animal models of obesity and hypertension.

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Section: *Statistically Significant Difference When Compared With Thementioning

confidence: 98%

The Zucker fatty rat as a genetic model of obesity and hypertension.

1989

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“…There are many animal -Original-models in which diabetes mellitus develops spontaneously, and its onset is usually secondary to hypoinsulinemia. In various strains of rat, obesity and insulin resistance secondary to leptin receptor deficiency induce diabetes [7,11,17,19]. Original WBN/Kob male rats spontaneously develop diabetes, although its onset is secondary to chronic pan-pancreatitis [2,13,20,22,24,29].…”

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confidence: 99%

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

et al. 2010

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Abstract:Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr fa ) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.

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“…These new models of obesity-diabetes should prove useful in dissecting the genetic control of beta-cell responses to hyperglycaemia and insulin resistance. [Diabetologia (2002) [6,7], SHR [8], and LA [9]. In rats, it seems that only obese males are subject to developing severe hyperglycaemia and contraction of beta-cell numbers.…”

mentioning

confidence: 99%

“…A similar degree of variant diabetes phenotypes have been observed in rats with a leptin receptor deficiency on various inbred Obesity is usually associated with abnormalities in carbohydrate metabolism. In rodents with genetic perturbations of the leptin/leptin receptor system, the obese phenotype is associated with glucose intoler-backgrounds: WKY [5], ZDF [6,7], SHR [8], and LA [9]. In rats, it seems that only obese males are subject to developing severe hyperglycaemia and contraction of beta-cell numbers.…”

mentioning

confidence: 99%

Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Lepr db ) and obese (DBA-Lep ob ) mice

Chua¹,

Liu

et al. 2002

Diabetologia

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Aims. Our goal was to identify genetic variants that determine the response to insulin resistance and hyperglycaemia. This report documents the diabetes syndrome of two new congenic strains of mice generated by the transfer of the Lepr db mutation to the FVB/NJ strain and the Lep ob mutation to the DBA/2J strain. Methods. Mice were characterised by measures of blood metabolites and hormones along with challenges with glucose and insulin injections. Histological examinations of the endocrine pancreas and the kidneys were also carried out. Results. Obese mice of the FVB-db congenic strain show long-term hyperglycaemia that is primarily due to severe insulin resistance. The hyperglycaemia in the fed state persists despite escalating secretion of insulin and massive increase of pancreatic beta cells. Obese FVB-db mice show evidence of mesangial matrix expansion, a hallmark of diabetic nephropathy.Leptin-deficient mice of the DBA-ob strain have variable obesity-diabetes. In mice with high insulin (>10 ng/ml), DBA-ob/ob mice maintain their increased adiposity and have a large increase in betacell number. In mice with low insulin (<1 ng/ml) DBA-ob/ob mice have greatly diminished adiposity. These mice have atrophied islets with evidence of increased beta-cell neogenesis from the ductal epithelium. Conclusions. The strain-specific responses suggest the existence of genetic variants that control insulin sensitivity and beta-cell responses in the strains described in this report. These new models of obesity-diabetes should prove useful in dissecting the genetic control of beta-cell responses to hyperglycaemia and insulin resistance. [Diabetologia (2002) [6,7], SHR [8], and LA [9]. In rats, it seems that only obese males are subject to developing severe hyperglycaemia and contraction of beta-cell numbers.The loss of beta cells in these obesity-diabetes models is not mediated by the immune system. Studies have shown that C57BLKS/J db/db (K-db) mice develop their characteristic diabetes phenotype independent of a functional immune system [10]. The response of the beta cell in these obese rodents is subject to dietary influences. When placed on a completely carbohydrate-free diet (CHO-free diet), obese C57BLKS/J db/db mice are able to maintain near-euglycaemia and preserve their pancreatic beta-cell mass [11].While these strain-specific phenotypes have been documented [4], some of the congenic strains have been lost. This report describes the generation and characterisation of several new congenic mouse strains carrying mutations of Lep or Lepr. The FVB congenic strains (FVB-db and FVB-ob) provide a new diabetes phenotype that has not been described previously. Obese FVB mice suffer a prolonged period of hyperglycaemia that produces massive expansion of beta-cell mass. We show data that the early onset of severe insulin resistance probably accounts for the hyperglycaemia of these strains. The islet hyperplasia of obese FVB mice suggests that prolonged hyperglycaemia does not eventually lead to complete betacell atro...

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Effect of dietary sucrose on the SHR/N-corpulent rat: a new model for insulin-independent diabetes

Cited by 93 publications

References 33 publications

The Zucker fatty rat as a genetic model of obesity and hypertension.

The Zucker fatty rat as a genetic model of obesity and hypertension.

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Lepr db ) and obese (DBA-Lep ob ) mice

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