Yucatan Miniature Swine as a Model for the Study of Human Diabetes Mellitus

Phillips, Roxanne; Panepinto, L M; Spangler, R. S.; Westmoreland, Nelson

doi:10.2337/diab.31.1.s30

Cited by 40 publications

(27 citation statements)

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“…Swine have been used extensively as a model of human in biomedical researches such as cardiovascular, metabolic and transplantation (Phillips et al, 1982;Larsen and Rolin, 2004;Imai et al, 2006;Groth, 2007). In the last decade, an increasing number of studies in the field of neuroscience has been reported (Lind et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The pig model in brain imaging and neurosurgery

Sauleau

Lapouble

Val‐Laillet

et al. 2009

Animal

212

178

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The pig model is increasingly used in the field of neuroscience because of the similarities of its brain with human. This review presents the peculiarities of the anatomy and functions of the pig brain with specific reference to its human counterpart. We propose an approximate mapping of the pig's cortical areas since a comprehensive description of the equivalent of Brodmann's areas is lacking. On the contrary, deep brain structures are received more consideration but a true three-dimensional (3D) atlas is still eagerly required. In the second section, we present an overview of former works describing the use of functional imaging and neuronavigation in the pig model. Recently, the pig has been increasingly used for molecular imaging studies using positron emission tomography (PET). Indeed, the large size of its brain is compatible with the limited spatial resolution of the PET scanner built to accommodate a human being. Similarly, neuronavigation is an absolute requirement to target deep brain areas in human and in pig since the surgeon cannot rely on external skull structures for zeroing the 3D reference frame. Therefore, a large body of methodological refinements has been dedicated to image guided surgery in the pig model. These refinements allow now a millimetre precision: an absolute requirement for basal nuclei targeting. In the third section, several examples of ongoing studies in our laboratory were presented to illustrate the intricacies of using the pig model. For both examples, after a brief description of the scientific context of the experiment, we present, in detail, the methodological steps required to achieve the experimental goals, which are specific to the porcine model. Finally, in the fourth section, the anatomical variations depending on the breed and age are discussed in relation with neuronavigation and brain surgery. The need for a digitized multimodality brain atlas is also highlighted.Keywords: pig, neuroimaging, single photon emission tomography, neuronavigation, deep brain stimulation ImplicationsThe pig model is increasingly used in the field of neuroscience because of the similarities of its brain with human. Indeed, aside from the rodent model there is a critical need for a large animal model ethically acceptable, i.e. excluding non-human primates. In this review we present some experiments dealing with the various procedures achievable in the pig model ranging from image-guided brain surgery to functional brain imaging studies. The recent advances in functional imaging data processing pointed out our partial knowledge of pig brain neuro-anatomy and the requirement for a digitalized atlas matching MRI (magnetic resonance imaging) and histological resources. IntroductionSwine have been used extensively as a model of human in biomedical researches such as cardiovascular, metabolic and transplantation (Phillips et al., 1982;Larsen and Rolin, 2004;Imai et al., 2006;Groth, 2007). In the last decade, an increasing number of studies in the field of neuroscience has been reported (Lind et ...

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Section: Introductionmentioning

confidence: 99%

The pig model in brain imaging and neurosurgery

Sauleau

Lapouble

Val‐Laillet

et al. 2009

Animal

212

178

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“…Indeed, pigs are, like man, recognised as an LDL species (Olsen et al 2002), and they transport a large part of their esterified cholesterol in this lipoprotein. Pigs are also omnivorous (Phillips et al 1982), their cardiovascular system is quite similar to that of man (Dixon et al 1999), and their human-like physiology (Moughan et al 1992) and physiopathology related to obesity, type 2 diabetes and CVD (Dixon et al 1999), as well as their large size, are very useful for mimicking the situation of obese people. The objective of the present study was to observe possible specific lipid -lipoprotein modulation in relation to the development of obesity induced during sexual maturation in a Yucatan mini-pig model of childhood obesity.…”

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confidence: 99%

“…Adult mini-pigs have already been used to study insulin resistance and lipid metabolism changes in relation to the Western lifestyle (Phillips et al 1982;Gerrity et al 2001). Even if pigs and mini-pigs, compared with man, have a very low activity of CETP and present low triacylglycerol plasma concentrations Olsen et al 2002), compared with mice and rats, pigs and mini-pigs represent one of the species most relevant for modelling lipoprotein metabolism in man.…”

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confidence: 99%

Obesity induced during sexual maturation is linked to LDL-triacylglycerols in Yucatan miniature swine

Sebért¹,

Lecannu²,

Sené³

et al. 2005

Br J Nutr

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The incidence of childhood obesity is rising dramatically throughout industrialised countries. To evaluate and study the impact of childhood obesity on lipoprotein metabolism, we developed a new animal model of premature obesity. Yucatan mini-pigs aged 4 months were studied over a 12-month period from childhood to adulthood. Animals were divided into two groups: the first group were overfed a Western misbalanced diet; the second group were normally fed a recommended human-type diet. Cholesterol and triacylglycerol concentrations in VLDL-, LDL-and HDL-lipoproteins were followed from baseline to adulthood by fast protein liquid chromatography. At 10 (the end of sexual maturation) and 16 months old (adulthood), liver, visceral and subcutaneous adipose tissues were sampled. Real-time RT-PCR was performed in order to compare apo AI, apo B, apo C-III, PPAR-a, insulin receptor and lipoprotein lipase gene expression between groups and ages. Differences between groups were observed only after sexual maturity. Adult overfed mini-pigs had a higher LDL-cholesterol:HDL-cholesterol ratio (P,0·05; 0·55 (SE 0·06) for overfed v. 0·42 (SE 0·04) for normally fed pigs at the tenth month of the study). In both groups, VLDL-triacylglycerol decreased (P,0·05). VLDL-triacylglycerol evolution in the overfed group was associated with an increase in LDL-triacylglycerol plasma concentrations (P,0·05) after sexual maturation. LDL-triacylglycerol concentration in overfed mini-pigs went from an average of 0·28 mmol/l before sexual maturation to reach an average concentration of 0·56 mmol/l afterwards. This phenomenon has never been observed in similar studies when obesity is induced in adult mini-pigs and may represent a specific hallmark of an obesity induced during sexual maturity.

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“…The mechanisms underlying the increased risk and greater acceleration and severity of atherosclerotic disease in diabetes remain an enigma due, at least in part, to the lack of suitable humanoid animal models (5,6). In this study, we chose to induce diabetes in an atherosclerotic swine model, which we have extensively characterized over the last two decades (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

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confidence: 99%

Diabetes-Induced Accelerated Atherosclerosis in Swine

et al. 2001

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Patients with diabetes are at higher risk for atherosclerotic disease than nondiabetic individuals with other comparable risk factors. Studies examining mechanisms underlying diabetes-accelerated atherosclerosis have been limited by the lack of suitable humanoid animal models. In this study, diabetes was superimposed on a well-characterized swine model of atherosclerosis by injection of the ␤-cell cytotoxin streptozotocin (STZ), resulting in a >80% reduction in ␤-cells and an increase in plasma glucose to diabetic levels. Animals were maintained without exogenous insulin for up to 48 weeks. Plasma glucose and cholesterol levels and lesion extent and severity were quantified in swine with diabetes and hyperlipemia alone and in combination compared with controls. Diabetes had no effect on plasma cholesterol levels, P atients with diabetes are at two-to sixfold greater risk of developing atherosclerosis than nondiabetic individuals (1,2), and the most common cause of death in adult diabetic patients is coronary heart disease (3). This excess risk occurs in both type 1 and type 2 diabetes (3). In contrast to nondiabetic subjects, heart disease in diabetic subjects appears earlier in life, affects women almost as often as men, and is more often fatal (3). As many as 80% of all type 2 diabetic patients will die of atherosclerotic macrovascular disease (4), and adult diabetic patients are more susceptible to developing other atherosclerotic risk factors, including hypertension and dyslipidemias (3). Furthermore, data on the efficacy of insulin control of diabetes in ameliorating atherosclerotic disease are inconsistent. Although improvement of glycemic control may reduce the risk of heart disease in type 1 diabetic patients (3), insulin-treated type 2 diabetic patients continue to have increased risk of cardiovascular events (3).The mechanisms underlying the increased risk and greater acceleration and severity of atherosclerotic disease in diabetes remain an enigma due, at least in part, to the lack of suitable humanoid animal models (5,6). In this study, we chose to induce diabetes in an atherosclerotic swine model, which we have extensively characterized over the last two decades (7-15). Swine has proven to be an excellent model for cardiovascular studies, in that the development, morphology, and function of the normal cardiovascular system in swine closely resembles that of humans (16). Swine are also, like humans, omnivores, develop spontaneous atherosclerosis with increased age (17), and have lipoprotein profiles and metabolism similar to humans (7,18 -20). When fed cholesterol-and lipidcontaining diets, they develop humanoid atherosclerosis in most arterial beds in time periods inversely proportional to cholesterol level (7)(8)(9)(10)(11)(12)(13)(14)21). Therefore, by use of streptozotocin (STZ) as a diabetes-inducing agent that we superimposed on the atherosclerotic swine model, we set out to determine the following: 1) whether diabetes could be reproducibly produced and maintained over prolonged time periods in...

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Yucatan Miniature Swine as a Model for the Study of Human Diabetes Mellitus

Cited by 40 publications

References 0 publications

The pig model in brain imaging and neurosurgery

The pig model in brain imaging and neurosurgery

Obesity induced during sexual maturation is linked to LDL-triacylglycerols in Yucatan miniature swine

Diabetes-Induced Accelerated Atherosclerosis in Swine

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