Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism.
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 microg/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.
Jensen-Waern
M
M
Department of Clinical Sciences, Section for Comparative Physiology and Medicine, SLU, PO Box 7054, 750 07 Uppsala, Sweden. Marianne.Jensen-Waern@kv.slu.se
Andersson
M
M
Kruse
R
R
Nilsson
B
B
Larsson
R
R
Korsgren
O
O
Essén-Gustavsson
B
B
D000409:Alanine / Q000097:blood; D000596:Amino Acids / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006943:Hyperglycemia; D007328:Insulin / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013552:Swine; D013654:Taurine / Q000097:blood
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D013654:Taurine; D000409:Alanine