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

Abstract

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.

Insulin treatment of streptozotocin-induced diabetes re-establishes the patterns in carbohydrate, fat and amino acid metabolisms in growing pigs

“…After STZ injection the pigs showed polyuria/polydipsia, which was resolved by insulin treatment. Non-insulintreated STZ-diabetic pigs in the present study showed low DWG, in accordance with previous observations by Jensen-Waern et al 6 However, after the onset of insulin treatment, the DWG was at least as good as that of conventional high-health pigs.…”

“…After acclimatization, the pigs underwent surgery and an indwelling silicon catheter (SIL-C70 with round tip; Instec Solomon, Plymouth Meeting, PA, USA) was inserted into their vena jugularis dexter under aseptic conditions. STZ was given intravenously according to Jensen-Waern et al 6 In brief, anaesthesia was induced with a combination of medetomidine (Domitor Õ vet, 1 mg/mL; Orion Pharma Animal Health, Sollentuna, Sweden) at a dose of 0.05 mg/kg BW, and tiletamine and zolazepam (Zoletil Õ , 250 mg/mL; Virbac, Reading, Carros, France) at a dose of 5 mg/kg BW intramuscularly.…”

Type 2 diabetes affects postextraction socket healing and influences first‐stage implant surgery: A study based on clinical and animal evidence

“…The average blood glucose value of the T2DM group remained stable during the four‐month study period. We believe that the dosage (150 mg/kg) of the STZ injection was safe and could achieve balance in the damaged pancreatic β‐cells …”

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

“…27 To meet the criteria set by the World Health Organization for diabetes and to define diabetes, the fasting blood glucose level was measured, and an intravenous glucose tolerance test (IvGTT) was performed.…”