Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs: effects of metformin at isoenergetic feeding in a type 2-like diabetic pig model.

Insulin-mediated glucose metabolism was investigated in streptozotocin (STZ)-treated diabetic pigs to explore if the STZ-diabetic pig can be a suitable model for insulin-resistant, type 2 diabetes mellitus. Pigs (approximately 40 kg) were meal-fed with a low-fat (5%) diet. Hyperinsulinemic (1, 2, and 8 mU kg(-1) min(-1)) clamps and/or 6,6-(2)H-glucose infusion studies were performed in 36 pigs. Diabetic (slow, 30-minute infusion of 130 mg STZ/kg) vs normal pigs were nonketotic, showed fasting hyperglycemia (21.7 +/- 1.1 vs 5.3 +/- 0.2 mmol/L), comparable plasma insulin (9 +/- 7 vs 5 +/- 1 mU/L), and elevated triglyceride concentrations (1.0 +/- 0.3 vs 0.2 +/- 0.1 mmol/L). After a standard meal, plasma triglycerides, cholesterol, and nonesterified fatty acid concentrations were significantly higher in diabetic vs normal pigs (1.2 +/- 0.3 vs 0.3 +/- 0.1, 2.3 +/- 0.2 vs 1.7 +/- 0.1, and 1.5 +/- 0.5 vs 0.2 +/- 0.1 mmol/L, respectively, P < .05). Fasting whole-body glucose uptake, hepatic glucose production, and urinary glucose excretion were increased (P < .01) in diabetic vs normal pigs (9.1 +/- 0.6 vs 4.8 +/- 0.4, 11.4 +/- 0.6 vs 4.8 +/- 0.4, and 2.3 +/- 0.2 vs 0.0 +/- 0.0 mg kg(-1) min(-1)). During hyperinsulinemic euglycemia (approximately 6 mmol/L), whole-body glucose uptake was severely reduced (P < .01) and hepatic glucose production was moderately increased (P < .05) in diabetic vs normal pigs (6.7 +/- 1.3 vs 21.1 +/- 2.2 and 1.7 +/- 0.5 vs 0.8 +/- 0.3 mg kg(-1) min(-1)) despite plasma insulin concentrations of 45 +/- 5 vs 24 +/- 5 mU/L, respectively. Metformin vs placebo treatment of diabetic pigs (twice 1.5 g/d) for 2 weeks during isoenergetic feeding (1045 kJ/kg body weight(0.75)) resulted in a reduction in both fasting and postprandial hyperglycemia (14.7 +/- 1.5 vs 19.4 +/- 0.6 and 24.9 +/- 2.2 vs 35.5 +/- 4.9 mmol/L), a reduction in daily urinary glucose excretion (approximately 250 vs approximately 350 g/kg food), and an increase in insulin-stimulated glucose disposal (9.4 +/- 2.2 vs 5.8 +/- 1.7 mg kg(-1) min(-1); P < .05), respectively. In conclusion, a slow infusion of STZ (130 mg/kg) in pigs on a low-fat diet induces the characteristic metabolic abnormalities of type 2 diabetes mellitus and its sensitivity to oral metformin therapy. It is therefore a suitable humanoid animal model for studying different aspects of metabolic changes in type 2 diabetes mellitus. Insulin resistance in STZ-diabetic pigs is most likely secondary to hyperglycemia and/or hyperlipidemia and therefore of metabolic origin.

Surplus dietary tryptophan reduces plasma cortisol and noradrenaline concentrations and enhances recovery after social stress in pigs.

Social stress occurs in intensive pig farming due to aggressive behavior. This stress may be reduced at elevated dietary levels of tryptophan (TRP). In this study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to large neutral amino acid (LNAA) ratios on behavior and stress hormones in catheterized pigs ( approximately 50 kg BW), which were exposed to social stress by placing them twice into the territory of a dominant pig ( approximately 60 kg) for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6 micromol/l (p<0.01) in pigs on the high vs. normal TRP diets, respectively. Pre-stress plasma cortisol and noradrenaline concentrations were twofold (p<0.01) and 1.4-fold (p<0.05) lower but plasma adrenaline concentration was similar in pigs on the high vs. normal TRP diets, respectively. During the social confrontations, pigs on the high vs. normal TRP diets show a tendency towards reduced active avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, p<0.1) but their physical activity (8.5+/-0.6 vs. 10.2+/-0.8 min) and aggressive attitude towards the dominant pig (11+/-3 vs. 7+/-2 times biting) were similar. Immediate (+5 min) post-stress plasma cortisol, noradrenaline and adrenaline responses were similar among dietary groups. After the social confrontations, the post-stress plasma cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min to 2 h) were lower/steeper (p<0.05) in pigs on the high vs. normal TRP diets. In summary, surplus TRP in diets for pigs (1) does not significantly affect behavior when exposed to social stress, (2) reduces basal plasma cortisol and noradrenaline concentrations, (3) does not affect the immediate hormonal response to stress, and (4) reduces the long-term hormonal response to stress. In general, pigs receiving high dietary TRP were found to be less affected by stress.

Diurnal rhythms in plasma cortisol, insulin, glucose, lactate and urea in pigs fed identical meals at 12-hourly intervals.

Diurnal rhythms in plasma cortisol, insulin, glucose, lactate and urea concentrations were investigated in eight catheterized pigs of approximately 35 kg BW. Pigs were fed isoenergetic/isoproteinic diets at a restricted level (2.5 x maintenance requirement for energy) in two daily rations (06:00 and 18:00 hours) in order to obtain equal intervals between feed intake. Preprandial plasma cortisol concentration was 22+/-3 ng/mL in the morning and 14+/-2 ng/mL in the evening (p<0.025), whereas the concentrations of insulin, glucose, lactate, and urea were similar. In the postprandial period in the morning (06:00-09:00 hours) plasma cortisol, insulin and lactate concentrations (expressed as the total area under the curve) were greater (p<0.001) compared to the evening (18:00-21:00 hours) by 100%, 42%, and 24%, respectively, while postprandial plasma glucose and urea concentrations were not affected by time of the meal. When postprandial plasma concentrations were expressed as a response over preprandial concentrations (decremental or incremental area under the curve), the diurnal rhythm was not observed for cortisol and glucose, persisted for insulin and lactate, and appeared for urea with a smaller postprandial urea response (p<0.05) in the morning compared to the evening. We conclude that the diurnal rhythm in plasma cortisol is independent of feeding whereas the diurnal rhythms in plasma insulin, lactate and urea are unveiled by the morning/evening meals in pigs. At equal 12-h intervals between meals, the postprandial responses of lactate and urea show diurnal variations, each in a specific manner, which suggest decreased postprandial efficiency of carbohydrate metabolism and increased postprandial efficiency of protein metabolism in the morning compared to the evening.

Parameters and techniques to determine intestinal health of poultry as constituted by immunity, integrity, and functionality.

The intestinal microflora lives in intimate contact with its surrounding intestinal wall and the bacteria can exert beneficial or deleterious effects on the host, depending on whether they are classified as probiotics or as pathogens. The interaction is determined on one hand by characteristics of the microorganisms, and on the other hand by characteristics of the intestinal wall. Together they determine the health status of the intestine. This review describes parameters and techniques (with advantages and disadvantages) available for poultry to identify the characteristics of the intestinal health, as constituted by three components: immunity, integrity, and functionality. To investigate intestinal immunity, in situ detection of various cell populations of the immune system with specific monoclonal antibodies using immunocytochemical staining is a reliable, semi-quantitative method. In vitro assays to measure functional aspects of T lymphocytes, B lymphocytes, plasma cells, natural killer cells, macrophages, and phagocytes are applicable to intestinal wall tissue. For investigation of intestinal integrity, in situ detection of villous height and crypt depth and their ratio, and villus arrangement is still an easy, routine histological method. In addition, expression levels of specific molecules, such as E-cadherin, different growth factors, and trefoil factor, seem promising parameters. To investigate functionality of the intestine, the permeability can be measured as the rate of transport of tracer molecules across the epithelial surface. Furthermore, determination of the level of mucus secretion and its composition are a valuable tool. These parameters for immunity, integrity and functionality, or a combination thereof, are indispensable to investigate the influence of intestinal microorganisms on intestinal health.