Genetic Selection for Diabetogenic Traits in Yucatan Miniature Swine

Phillips, Robert W.; Panepinto, L M; Will, D. H.

doi:10.2337/diab.28.12.1102

Cited by 16 publications

(10 citation statements)

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“…63 (2) Metabolism of foodstuffs, 63 specifically lipoprotein metabolism (References 24, 25, and 51 and the present report), is similar to that in humans. (3) Swine have a propensity toward sedentary habits and obesity; unlike dogs, which will pace in their cages if not adequately exercised, pigs are content to be sedentary.…”

Section: Need For a Suitable Animal Model: Advantages Of The Porcine supporting

confidence: 67%

Dyslipidemia and Vascular Dysfunction in Diabetic Pigs Fed an Atherogenic Diet

Dixon

Stoops

Parker

et al. 1999

ATVB

126

140

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Abstract-Diabetic patients typically have not only hyperglycemia but also dyslipidemia. Study of the pathogenic components of the diabetic milieu and mechanisms of accelerated atherosclerosis is hindered by inadequate animal models. A potentially suitable animal model for human diabetic dyslipidemia is the pig, because it carries a large fraction of total cholesterol in low-density lipoprotein (LDL), similar to humans. In this study, male Sinclair miniature pigs were made diabetic by destroying the insulin-producing cells of the pancreas with alloxan and then were fed a high fat and high cholesterol diet for comparison with pigs fed a nondiabetic high fat and high cholesterol diet and control pigs. Diabetic pigs exhibited hyperglycemia, but plasma urea nitrogen, creatinine, and transaminase levels were in the normal range, indicating no adverse effects on kidney and liver function. The lipoprotein profile in diabetic pigs was similar to that found in human diabetic patients and was characterized by hypertriglyceridemia (2.8-fold increase versus control and high fat-fed pigs) and a profound shift of cholesterol distribution into the LDL fraction (81%) versus the distribution in high fat-fed (64%) and control (57%) pigs. LDL particles were lipid-enriched and more heterogeneous in diabetic pigs. Apolipoprotein B was distributed among a much broader spectrum of LDL particles, and apolipoprotein E was partially redistributed from high-density lipoprotein to apolipoprotein B-containing lipoproteins in diabetic pigs. There was little change in apolipoprotein A-I distribution. Diabetic pigs showed several early signs of excess vascular disease. In diabetic pigs, 75% of the coronary artery segments showed contractile oscillations in response to prostaglandin F 2␣ compared with 25% in high fat-fed pigs and 10% in control pigs. Endothelium-dependent relaxation of brachial arteries was nearly abolished in diabetic pigs but unchanged in high fat-fed versus control pigs. Carotid artery Sudan IV staining for fatty streaks was significantly increased only in diabetic pigs. This porcine model should provide insights into the etiology of human diabetic dyslipidemia and facilitate study of peripheral vascular and coronary artery disease in diabetic patients.

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Section: Need For a Suitable Animal Model: Advantages Of The Porcine supporting

confidence: 67%

Dyslipidemia and Vascular Dysfunction in Diabetic Pigs Fed an Atherogenic Diet

Dixon

Stoops

Parker

et al. 1999

ATVB

126

140

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“…Attempts to genetically select a strain of diabetic pigs have been made (38,39,40) but have, so far, not been confirmed to be successful (19). The use of pancreatectomized animals as a model of diabetes (15,33,34,50) has the disadvantage of also removing the exocrine function of the pancreas and the non-␤-cell endocrine cells of the islets of Langerhans, and although performance of partial pancreatectomy might be useful for induction of mild diabetes, this method clearly is more invasive compared with the administration of STZ.…”

Section: Discussionmentioning

confidence: 99%

“…Of special interest for the study of diabetes is the similarities to humans found in the clinical chemistry (7,10,12,14,24,26,55), nutrition and gastrointestinal tract (4,8,11,20,35,40,51), pancreas development and morphology (21,36,37,44,49,54), and metabolism (3, 35). These characteristics make swine an interesting species for studies of metabolic abnormalities in diabetes.…”

mentioning

confidence: 99%

Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes

Larsen

Wilken

Gotfredsen

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

113

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Intermediate NIA doses induced moderate changes of glucose tolerance [glucose area under the curve increased from 940 Ϯ 175 to 1,598 Ϯ 462 mM ⅐ min, P Ͻ 0.001 (100 mg/kg) and from 890 Ϯ 109 to 1,669 Ϯ 691 mM ⅐ min, P ϭ 0.003 (67 mg/kg)] with reduced insulin secretion [1,248 Ϯ 602 pM ⅐ min after 16 days and 1,566 Ϯ 190 pM ⅐ min after 60 days vs. 3,251 Ϯ 804 pM ⅐ min in normal animals (P Ͻ 0.001)] and ␤-cell mass [5.5 Ϯ 1.4 mg/kg after 27 days and 7.9 Ϯ 4.1 mg/kg after 60 days vs. 17.7 Ϯ 4.7 mg/kg in normal animals (P ϭ 0.009)]. The combination of NIA and STZ provided a model characterized by fasting and especially postprandial hyperglycemia and reduced, but maintained, insulin secretion and ␤-cell mass. This model holds promise as an important tool for studying the pathophysiology of diabetes and development of new pharmacological agents for treatment of the disease.in vivo pharmacology; large-animal model; glucose tolerance; ␤-cell reduction; glucose-stimulated insulin secretion.THE STUDY OF THE PATHOPHYSIOLOGY and treatment of diabetes requires well characterized animal models that resemble aspects of the disease in humans. Various forms of diabetes occur spontaneously or can be induced in several species of animals. Most of the available models are based on rodents; however, nonrodent models of diabetes are urgently needed as a valuable supplement to rodents for both practical and physiological reasons.The pig is useful as a model for human physiology and pathophysiology, because many organ systems resemble those of the human. Of special interest for the study of diabetes is the similarities to humans found in the clinical chemistry (7,10,12,14,24,26,55), nutrition and gastrointestinal tract (4,8,11,20,35,40,51), pancreas development and morphology (21,36,37,44,49,54), and metabolism (3, 35). These characteristics make swine an interesting species for studies of metabolic abnormalities in diabetes. The Göttingen minipig is especially suitable for long-term studies because of its small size and ease of handling, even at full maturity (6).Pancreatectomy has been investigated as a method of inducing diabetes in pigs (33,34,50,55). However, high rates of mortality have been observed postoperatively (50, 55), meaning that this technique should be used with great caution, and alternatives should be considered because of welfare considerations. Chemical induction of diabetes offers the advantage of preservation of both exocrine and endocrine cell populations other than ␤-cells, thus resembling the situation in human diabetes (55). Several stable models have been established for overt type 1 diabetes in the pig by the use of pharmacological induction of ␤-cell damage with streptozotocin (STZ), either as single or repeated injections (2, 15, 16, 27-29, 46, 55). Substantially increased fasting plasma glucose (FPG) levels and decreased insulin secretion in response to glucose stimuli have been obtained as well as increases in plasma triglycerides and total cholesterol (27,29). Late complications typical of diabetes, such...

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“…Large animals with spontaneous diabetes include the monkeys (Macaca nigra, Saimiri sciureus, squirrel monkey, Macaca mulatta, and occasional others 9 ), dogs, [golden retrievers (G. A. Padgett, personal communication) and Keeshonds 10 ], Yucatan miniature pigs, 11 and certain rabbits. 12 this symposium).…”

Section: Availabilitymentioning

confidence: 99%

Metabolic and Underlying Causes of Diabetes Mellitus

Grodsky¹,

Anderson²,

Coleman³

et al. 1982

Diabetes

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It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements.Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines. DIABETES 31 (Suppl. 1):45-53, 1982.

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Genetic Selection for Diabetogenic Traits in Yucatan Miniature Swine

Cited by 16 publications

References 0 publications

Dyslipidemia and Vascular Dysfunction in Diabetic Pigs Fed an Atherogenic Diet

Dyslipidemia and Vascular Dysfunction in Diabetic Pigs Fed an Atherogenic Diet

Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes

Metabolic and Underlying Causes of Diabetes Mellitus

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