The effects of alloxan diabetes on Yucatan miniature swine and their progeny

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

doi:10.1016/0026-0495(80)90096-7

Cited by 11 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of action is similar to STZ (Yamamoto et al 1981), and their diabetogenic actions are very similar (Junod et al 1967;Rerup and Tarding 1969). ALX has also been used for induction of diabetes in Yucatan and Göttingen minipigs; doses around 100 to 200 mg/kg result in severe diabetes (Boullion et al 2003;Dixon et al 1999;Otis et al 2003;Phillips et al 1980). ALX in a dose of 80 mg/kg has been reported to induce diabetes with moderate hyperglycemia and partial loss of beta-cell mass in Göttingen minipigs (Kjems et al 2001).…”

Section: Chemical Induction Of Diabetesmentioning

confidence: 96%

Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

Larsen¹,

Rolin²

2004

ILAR Journal

168

115

View full text Add to dashboard Cite

Animal models of type 1 diabetes remain essential tools for investigation of the etiology and pathogenesis of the disease and, importantly, for the development of effective new treatments. Although a range of well-characterized and widely used models of type 1 diabetes in rodents are currently available, large animal models are a valuable complement to rodent models for both physiological and practical reasons. The pig is very useful in many aspects as a model for human physiology and pathophysiology because many organ systems of this species, as well as physiological and pathophysiological responses, resemble those of the human. The Göttingen minipig is particularly suitable for long-term studies because of its inherent small size and ease of handling, even at full maturity. Of particular relevance to the field of type 1 diabetes are the many similarities evident between humans and pigs with regard to pharmacokinetics of compounds after subcutaneous administration, structure and function of the gastrointestinal tract, morphology of the pancreas, and the overall metabolic status of the two species. Because spontaneous type 1-like diabetes is very rare in pigs, a model of the condition must be induced experimentally, either surgically or chemically. This process is discussed, and the use of the pig as a model in islet transplantation and diabetic complications is briefly summarized.

show abstract

Section: Chemical Induction Of Diabetesmentioning

confidence: 96%

Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

Larsen¹,

Rolin²

2004

ILAR Journal

168

115

View full text Add to dashboard Cite

show abstract

“…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 as capillary basement membrane thickening and cataracts, have also been shown in diabetic minipigs (28,41).In other studies, alloxan has been used for induction of diabetes in pigs (11,25,41). This compound, which has ␤-cell-toxic properties similar to those of STZ, in a dose of 200 mg/kg in Yucatan minipigs induced severe diabetes with high mortality due to hypoglycemia following acute hyperinsulinemia as a consequence of massive ␤-cell damage (41).…”

mentioning

confidence: 98%

“…In other studies, alloxan has been used for induction of diabetes in pigs (11,25,41). This compound, which has ␤-cell-toxic properties similar to those of STZ, in a dose of 200 mg/kg in Yucatan minipigs induced severe diabetes with high mortality due to hypoglycemia following acute hyperinsulinemia as a consequence of massive ␤-cell damage (41).…”

mentioning

confidence: 99%

“…This compound, which has ␤-cell-toxic properties similar to those of STZ, in a dose of 200 mg/kg in Yucatan minipigs induced severe diabetes with high mortality due to hypoglycemia following acute hyperinsulinemia as a consequence of massive ␤-cell damage (41). Doses of 80 mg/kg have been reported to induce mild diabetes with moderate hyperglycemia and partial loss of ␤-cell mass with impaired insulin secretion rates but normal fasting insulin levels in Göttingen minipigs (25).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

“…However, animal models are a valuable research tool for examining the relation between beta-cell mass, function and morphology on the one hand and insulin It is well documented that insulin concentrations show large amplitude oscillations in the peripheral circulation with a periodicity of 5 to 15 min [1,2,3], and it has been shown that these oscillations are of importance for insulin action in liver [4], muscle [5,6] and adipose tissues [7]. Since Type II (non-insulin-depenresistance on the other, because carefully controlled studies can involve surgical [10,11,12] or toxicological [10,13,14,15,16,17] induction of diabetes and long-term maintenance on experimental diets can induce insulin resistance and lipotoxicity [18,19,20,21]. An animal model should ideally allow peripheral sampling to assess pulsatility, so that invasive surgery to access portal sampling can be avoided.…”

mentioning

confidence: 99%

The conscious Göttingen minipig as a model for studying rapid pulsatile insulin secretion in vivo

Elander

Sturis

et al. 2002

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. Pulsatile secretion is important for insulin action and suitable animal models are important tools for examining the role of impaired pulsatile insulin secretion as a possible link between beta-cell mass, function and morphology and insulin resistance. This study examines the vascular sampling site, insulin kinetics, pulsatility and the response to glucose pulse entrainment to evaluate the Göttingen minipig as a model for studying pulsatile insulin secretion. Methods. Basal and glucose entrained insulin secretion was examined in normal minipigs and evaluated by autocorrelation, cross correlation and deconvolution. Results. Cross correlation showed a relation between oscillations in insulin concentrations in the portal and jugular vein in anaesthetised animals (p<0.001 in all animals), confirming the usefulness of jugular vein sampling for pulse detection. Jugular vein sampling in conscious animals showed obvious oscillations allowing estimates of burst shape and insulin kinetics. Glucose entrainment improved the pulsatile pattern (autocorrelation: 0.555±0.148 entrained vs 0. 350±0.197 basal, p=0.054). Deconvolution analysis resolved almost all insulin release as secretory bursts (69±20 basal vs 99.5±1.2% entrained, p<0.01) with a pulse interval (min) of 6.6±2.2 (basal) and 9.4±1.5 (entrained) (p<0.05) and a pulse mass (pmol/l per pulse) which was higher after entrainment (228±117 vs 41.2±18.6 basal, p<0.001). Conclusion/interpretation. The ability to fit kinetic parameters directly by deconvolution of peripheral endogenous insulin concentration time series in combination with the suitability of jugular vein sampling, rapid kinetics and entrainability makes the Göttingen minipig ideal for mechanistic studies of insulin pulsatility and its effects on insulin action. [Diabetologia (2002[Diabetologia ( ) 45:1389[Diabetologia ( -1396 Keywords Pulsatile insulin secretion, insulin kinetics, deconvolution, in vivo model, insulin action. dent) diabetes mellitus is characterized by defects in both insulin secretion and action, impaired pulsatile secretion could be an important link between beta-cell malfunction and impaired insulin action [8]. When addressing the cause of these impairments in humans, studies are often influenced by long-term impaired metabolism, and therefore demonstrate that defects could be secondary. This problem can, to some extent, be circumvented by studying first degree relatives of diabetic patients who are at risk of the disease but are still not affected by the effects of hyperglycaemia [9]. However, animal models are a valuable research tool for examining the relation between beta-cell mass, function and morphology on the one hand and insulin It is well documented that insulin concentrations show large amplitude oscillations in the peripheral circulation with a periodicity of 5 to 15 min [1,2,3], and it has been shown that these oscillations are of importance for insulin action in liver [4], muscle [5,6] and adipose tissues [7]. Since Type II (non-insulin-depen-

show abstract

The effects of alloxan diabetes on Yucatan miniature swine and their progeny

Cited by 11 publications

References 12 publications

Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

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

The conscious Göttingen minipig as a model for studying rapid pulsatile insulin secretion in vivo

Contact Info

Product

Resources

About