Insulin resistance is a state in which the biological effect of insulin is reduced when its concentration decreases or when a compensatory mechanism increases its concentration. Insulin resistance is characterized by reduced insulin response to glucose, i.e. decreased pancreatic beta cell function (insulin hyporesponsiveness) and/or reduced sensitivity of glucose to insulin (reduced intake of glucose by peripheral tissues under the influence of insulin-eng. insulin sensitivity). Methods for estimating insulin resistance include direct methods (hyperinsulinaemic-euglycaemic clamp, golden standard), indirect methods (intravenous glucose tolerance test) and surrogate methods (indices calculated from basal concentrations of insulin, glucose, NEFA and BHB-HOMA, QUICKI, RQUICKI and RQUICKI-BHB). Surrogate indices show correlations with direct and indirect test results but they are inconsistent. Inconsistency occurs because the dependence of glucose concentrations on the degree of hepatic gluconeogenesis should be kept in mind when evaluating insulin resistance in ruminants. Therefore, the hyperinsulinaemic-euglicaemic clamp method is particularly suitable as it excludes gluconeogenesis in hepatocytes from analysis. Our results have shown a correlation between HOMA, QUICKI and RQUICKI indices and metabolic profile parameters. The correlation between dynamic and basal responses of NEFA, BHB, insulin, glucose and inorganic phosphorus is significantly dependent on RQUICKI-BHB index values in

Background: Early lactation is period followed by changed metabolism in organism of the cow. This is the consequence of negativ energy balance, metabolic stress and milk production. Early lactation is characterised by high lipide catabolism (high NEFA) and low anabolic capacity (low insulin and IGF-I concentration). The aim of this study is to examine differences in metabolic adaptation of cows in early lactation (eight weeks after calving) in accordance to anabolic (insulin, IGF-I) and catabolic (NEFA) indicators in first week after calving.Materials, Methods & Results: The experiment included 50 Holstein-Friesian cows. Blood samples were collected in first, second, fourth and eight week after calving by venepunction of v.coccigea. Based on median value of indicator, cows were significantly (P < 0.001) classified in two groups: cows under metabolic stress (indicators of anabolism below the median Me-: indicators of catabolism above the medianMe+) and cows in control group (indicators of anabolism above the median Me+: indicators of catabolism under median Me-). Following criteria for comparison were given: based on classification of cows according to one indicator of metabolic load (insulinMe-:insulinMe+; IGF-IMe-:IGF-IMe+ and NEFAMe-:NEFA Me+); based on classification of cows according to combination of two indicators (insulinMe-+NEFAMe+: insulinMe++NEFAMe- and IGF-IMe-+NEFAMe+:IGF-IMe++NEFAMe-). Cows loaded with metabolic stress showed significan difference in metabolic adaptation in relation to control group (P < 0.05 or P < 0.01): higher values of STH, BHB (criteria were insulin, IGF-I, NEFA, insulin+NEFA, IGF-I+NEFA), higher values of bilirubin, AST, ALT, GGT, AP (criteria NEFA and IGF-I+NEFA) and MDA (criteria NEFA) and lower levels of glucose, total proteins, albumin (criteria IGF-I, NEFA, IGF-I+NEFA and body condition (criteria insulin, IGF-I, NEFA, insulin+ NEFA, IGF-I+ NEFA) were noted. Differences were expressed the most in first two weeks after calving. Differences in the body condition were the most notable later in weeks. Usage of NEFA indicator in first week after calving allows the most quality recognition of cows with metabolic parameters in extreme quartiles (ROC AUC= 0.87, P < 0.01) in first eight week of lactation.Discussion: Inverse relation betwen NEFA with insulin and IGF-I is consequence of next phisiological concept: plasma insulin and IGF-I decrease in same mannure after calvig and insulin aplication increase IGF-I; low insulin concentration leads cow to lipolysis and low IGF-I leads to STH resistance with increase concentration of STH and high lipolysis. Catabolism of adipose tissue and high NEFA concentration is most important for metabolic adaptation in periparturient period. Cows with insulin resistance, ketosis and fatty liver with many problems in metabolic adaptation showed high NEFA concentration. Atenuation of NEFA by niacin or anti-inflammatory drug decreases metabolic change due to high lipide mobilisation in early lactation. Low antepartal IGF-I showed significant effect on postpartum health, but our measuremens are in first week postpartum. In addition, increase catabolism of lipide viewed in NEFA value contributes to metabolic variation and adaptation in the first eight weeks of lactation much more than decrease of anabolic indicators such as insulin and IGF-I. The combination of the indicators does not lead to better recognition of cows with extreme metabolic change in relation to classification only to the value of NEFA.

The aim of this study was to determine to relationship between glucose, insulin, non-esterified fatty acid (NEFA) and indices of insulin resistance in the dry period (DP) and early lactation (EL). The importance of this study was in determining the relation between insulin sensitivity in DP and insulin resistance in EL. A total of 30 normally fed Holstein-Friesian cows with a high body condition score (> 3.75) were included in the study. Blood samples were collected in DP (weeks 5-7 ante partum) and EL (weeks 1-2 post partum). Cows in EL showed higher insulin resistance in comparison to DP due to a lower concentration of glucose and insulin, higher concentration of NEFA, lower value of revised quantitative insulin sensitivity check index and higher values of glucose:insulin and NEFA:insulin ratios (lower pancreas responsivnes to glucose and antilipolytic effect of insulin). Higher concentrations of insulin and glucose in the DP lead to a decrease in their concentrations and an increase in glucose:insulin and NEFA:insulin ratios in the EL. The revised quantitative insulin sensitivity check index in DP negatively correlates with the same index in EL, while positively correlating with the NEFA and NEFA:insulin ratio in EL. The EL revised quantitative insulin sensitivity check index value was influenced by dynamic changes (DP minus EL) in the insulin, NEFA, and glucose concentrations. The relationship between the indicators shows that higher insulin sensitivity in the DP increases resistance in EL in normally fed obese dairy cows.

Abstract:The aim of this study is to determine correlation between change in milk production and metabolic adaptation of cows during heat-stress. Experiment included 30 Holstein-Frisian cows. Cows exposed to heat-stress, which is expressed in high THI index, have lower milk production, higher concentration of insulin and lover concentrations of glucose and NEFA. Indexes of insulin resistance-RQUICKI, insulin: glucose and insulin: NEFA relations are higher in cows under heat stress. Grouping cows in accordance to reduced milk yield have showed that trend of reduction of glucose and NEFA levels, followed by increased insulin level, higher RQUICKI, greater insulin: glucose and insulin: NEFA ratios, started and increased during the reduction in milk production. Among this, significant correlation was founded between these parameters and milk yield. Significant correlation was also noted between those parameters. Change in metabolic value is of great importance for prediction of cows that would have decreased milk yield (above 18%). With almost 90% certainty cows with great reduction in milk yield can be detected. These cows have had following relative changes in values of metabolic parameters during heat-stress compared to thermo-neutral period: insulin increased for ≥12.5%, reduction in NEFA values for ≤14.1%, reduction in glucose for 21.5%, RQUICKI index increased for ≥9.6%, insulin: NEFA ratio increased for ≥20.1% and insulin: glucose for ≥20.3%. Dynamical changes in metabolites and insulin resistance Received 12 October 2017 Accepted 19 October 2017Acta Agriculturae Serbica, Vol. XXII, 44(2017); 123-131 124 values have great influence on milk yield in cows under heat stress. Decreasing in glucoses followed by increased insulin level and increased insulin sensitivity indicate that glucose is transferred from udder to other tissues which can cause decreased milk production.

Background: Insulin resistance is a state that is characterized with reduced sensitivity of peripheral tissues to insulin. It can be related with increased level of tumor necrosis factor alpha (TNF-α) in dogs. Insulin resistance can be evaluated by homeostasis model assessment (HOMA-IR, HOMA-β). The aim of this study was to determine correlation of circulating TNF-α level with insulin production and insulin resistance indexes in euglycaemic dogs. Materials, Methods & Results: Seventydogs of normal body score were included in this study. After blood sampling levels of glucose, insulin and TNF-α were determined and indexes HOMA-IR and HOMA-β were calculated. Three groups in accordance to TNF-α levels were formed: the first-TNF-α 0-2.0 pg/mL, the second-TNF-α below median (2.1-17.0 pg/mL) and the third-TNF-α above median (17.1-51.8 pg/mL). Differences in insulin and glucose levels, HOMA-IR and HOMA-β were determined in all three groups. ANOVA and posthock LSD analyses were used. Correlation between HOMA-IR and HOMA-β was determined. Linear regression between HOMA-β/HOMA-IR ratio and glucose concentration was calculated. SPSS statistical program was used (IBM). Highest insulin level was detected in the second group and the lowest was detected in the third group. The lowest glucose level was detected in the first group. The highest value of HOMA-β index was noted in the first group and it decreases with TNF-α increase. The highest HOMA-IR value was detected in the second group and the lowest was in the third group. Positive correlation was noted between HOMA-IR and HOMA-β. Significant linear correlation was noted between glucose levels in function of HOMA-β/HOMA-IR (R2= 0.51-0.78, P = 0.0007). The first group showed the minor change of glucose level (b= 0.29 mmol/L). In the third group the greatest change of glucose level in function of HOMA-β/HOMA-IR was noted (b= 0.52 mmol/L). In the third group the highest increase of glucose level followed by decrease in HOMA-β/HOMA-IR ratio was noted.  Discussion: Increase of TNF-α followed by increase of insulin was noted in the second group. That indicates reduced insulin action and compensatory increase in his concentrations in order to achieve the same effect. TNF-α induces reduction in expression of glucose transporter 4 that is insulin-regulating hormone. Serine phosphorylation of insulin receptor substrate-1 that is induced by TNF-α causes inhibition of insulin receptors. These actions cause insulin resistance and compensatory increase in insulin secretion. Increased tissue resistance is reflected in increased HOMA-IR index which is directly associated with insulin and glucose level. Increase of insulin value and HOMA-IR index were noted in second group. This indicates the influence of TNF-α on insulin resistance. The lowest insulin level was noted in the third group of dogs. Decrease in production and secretion leads to reduction in circulating insulin and can be evaluated by HOMA-β index. The highest value of this index was noted in first group and decreases with TNF-α increase. This can be related with apoptotic effect that TNF-α has on beta- pancreatic cells. Increase of HOMA-β index causes increase of HOMA-IR. This is indication of increased peripheral resistance. Compensatory mechanism for that state is increased insulin secretion. Glucose level will increase more during increase of HOMA-IR and decrease of HOMA-β. This indicates that TNF-α regulates glucose level directly and explains differences in glucose concentrations in dogs with different concentrations of TNF-α showed. Values of insulin resistance indexes, glucose and insulin were affected by circulating concentration of TNF-α. The most unfavorable change in glucose concentration based on insulin production and tissue resistance was founded in dogs with the highest circulating TNF-α concentration in blood.