Streptozotocin Diabetes in Juvenile Pigs. Evaluation of an Experimental Model

Gäbel, H; Bitter-Suermann, H; Henriksson, Christen; Säve-Söderbergh, J; Lundholm, Kent; Brynger, H

doi:10.1055/s-2007-1013518

Cited by 43 publications

(38 citation statements)

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“…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%

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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Section: Discussionmentioning

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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“…Early attempts to induce insulin-dependent diabetes in pigs were not paricularly successful (O'Hea et al, 1971). However, recently reported attempts by Gabel et al (1985) using intravenous streptozotocin have been more successful. In this study we have examined two different methods of inducing diabetes in outbred pigs: total pancreatectomy and intravenous streptozotocin.…”

Section: Introductionmentioning

confidence: 99%

Induction and Management of Diabetes Mellitus in the Pig

Wilson

Dhall

Simeonovic

et al. 1986

Aust J Exp Biol Med

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Summary. Insulin-dependent diabetes mellitus was induced in the pig by pancreatectomy or by administration of intravenous streptozotocin (150 mg/kg). High post-operative morbidity and mortality in the panereatectomised animals made this method of inducing diabetes unsuitable for animals to be used in long term studies. By contrast, the good clinical state of animals after streptozotocin and the permanence of their diabetes indicated that these animals were suitable for long term studies such as those involving transplantation of pancreatic islet tissue. Techniques designed to facilitate the assessment and management of these animals included placement of an indwelling jugular venous catheter to enable blood samples to be obtained for metabolic studies, denervation of an area on the flank of the animal to enable insulin administration with minimum discomfort and denervation of an ear to enable blood samples to be obtained from the animal for glucose estimation in long term studies.

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“…injection of a single dose of 100-150 mg streptozotocin (STZ) has been shown to be a safe procedure for inducing type 1 diabetes. 3 Diabetic illness not only affects the carbohydrate and lipid metabolism (reviewed by Taylor and Agius 6 ) but also alters the metabolism of protein. In rats, STZ-induced diabetes has been found to result in a decrease in the rate of protein synthesis and an increase in its degradation.…”

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confidence: 99%

Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism

et al. 2009

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Streptozotocin (STZ) given intravenously destroys pancreatic beta cells and is widely used in animal models to mimic type 1 diabetes. The effects of STZ on the clinical state of health and metabolism were studied in six high health certified domestic pigs weighing 19 + 1.3 kg at the start of the experiment. A single STZ dose of 150 mg/kg of body weight successfully induced hyperglycaemia and alterations in amino acid metabolism. Within 9 h after STZ administration, the blood glucose values fell from 5.4 -7.5 mmol/L to 0.8 -2.2 mmol/L. Hypoglycaemia was treated with 0.5 g glucose/kg body weight. In all pigs, hyperglycaemia was produced 24 h after STZ treatment, and 3 days after STZ injection, the glucose concentration was .25 mmol/L. Mean C-peptide concentration was 0.25 + 0.16 mg/L since 2 days after STZ injection until the end of the study. The serum concentration of the branched-chain amino acids (BCAA) increased four-fold, and alanine and taurine decreased by approximately 70% and 50%, respectively, after STZ treatment. All but one pig remained brisk and the physical examination was normal except for a retarded growth rate and a reduction of the skeletal muscle. At the end of the study, the pigs were moderately emaciated. Postmortem examination confirmed muscle wasting and a reduction of abdominal and subcutaneous fat. In conclusion, STZ-induced diabetes in pigs fulfils the requirements for a good animal model for type 1 diabetes with respect to clinical signs of the disease and alterations in the carbohydrate and amino acid metabolism. Reliable and reproducible animal models are of great importance in diabetes research. Rodent models are widely used, 1 and pigs are suitable when large animal models are required. 2 A pig model can be valuable when repeated biopsies and blood samples are required, and in studies concerning possible therapeutic perspectives such as transplantation of islets.Since spontaneous diabetes is extremely rare in pigs, the disease has to be induced either surgically by pancreatectomy 3,4 or chemically. 5 In Swedish Landrace pigs, i.v. injection of a single dose of 100-150 mg streptozotocin (STZ) has been shown to be a safe procedure for inducing type 1 diabetes. 3Diabetic illness not only affects the carbohydrate and lipid metabolism (reviewed by Taylor and Agius 6 ) but also alters the metabolism of protein. In rats, STZ-induced diabetes has been found to result in a decrease in the rate of protein synthesis and an increase in its degradation. Further, elevations of branched-chain amino acids (BCAAs, i.e. leucine, isoleucine and valine) and decreases in the concentrations of glutamate, glutamine, alanine, glycine, proline, serine and threonine were observed in the blood.

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Streptozotocin Diabetes in Juvenile Pigs. Evaluation of an Experimental Model

Cited by 43 publications

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

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

Induction and Management of Diabetes Mellitus in the Pig

Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism

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