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

Abstract

The effects of streptozotocin (STZ) were studied in eight high-health herd-certified Yorkshire × Swedish Landrace pigs (32.5 ± 2.6 kg initial body weight [BW]), and an insulin treatment protocol was developed to re-establish their metabolisms. A single intravenous dose of 150 mg STZ/kg BW successfully induced hyperglycaemia and alterations in their fat and protein metabolisms. Within 13 h post-STZ treatment blood glucose concentration had fallen to a range of 1.3 to 4.7 mmol/L. Hypoglycaemia was promptly treated with 0.5 g glucose/kg BW intravenously. All the pigs became hyperglycaemic with blood glucose concentrations >23 mmol/L within 48 h post-STZ. Two days post-STZ serum C-peptide concentrations fell below 60 ρmol/L in all the pigs and remained below 96 ρmol/L for five weeks until the end of the study. The pigs were left untreated for one week after STZ injection. At the end of this week 13-fold and nine-fold increases in serum concentrations of triglycerides and non-esterified fatty acids, respectively, were observed. Also, at this time-point a three-fold increase in the concentration of branched-chain amino acids (BCAA) was observed, and alanine and taurine were decreased by approximately 70% and 40%, respectively. During the week when the pigs were untreated, a reduced weight gain was observed, but after the onset of insulin treatment the daily weight gain was at least as good as that of conventional high-health pigs. Then a subcutaneous treatment with short-acting insulin was initiated. The initial dose of 2/3 IU/kg BW daily, divided between two doses, was gradually increased to 1 IU/kg BW. Within three weeks, the insulin treatment restored the metabolic changes in carbohydrate, fat and protein metabolisms produced by the STZ. In conclusion, the results underscore the usefulness of this animal model in translational research as insulin treatment re-establishes the changes in carbohydrate, fat and amino acid metabolisms observed in STZ-diabetic pigs and resolves clinical signs of disease similar to those in humans.