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New Mexico State University New Mexico State University Background –Land in New Mexico • Small fraction urban or cultivated • Mostly rangelands – grasslands, shrublands, – woodlands, and forests • Rural community – depend on land use economic sustainability New Mexico State University Land in New Mexico • Invasive native shrubs – Crowds out other herbaceous plants – Control water & nutrient balance – Reduces habitat – Catastrophic fires – Restricts sustainability of communities Range one-seed juniper New Mexico State University New Mexico State University Insulin Resistance in Range Cows M.K. Petersen, S. Cox, D. Hawkins, C. Löest, S. Soto, S. Ivey, T. Mulliniks, R. Endecott, R. Waterman and J. Sawyer New Mexico State University Background • Real life problems • Corona Range & Livestock Research Center (CRLRC) CRLRC New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center Year d to first estrus 24-h milk prod kg Adj. 205-d WW, kg Pregnancy rate % 1995 93 6.7 240 97 1996 86 4.8 211 98 1997 101 6.1 232 81 1998 97 5.2 220 59 1999 63 7.5 229 93 2000 107 5.6 160 80 2001 121 6.4 194 86 2003 58 7.6 241 96 2004 77 8.5 241 95 2005 70 -- 219 89 2006 70 5.6 159 94 2007 81 6.4 220 96 New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center Year d to first estrus 24-h milk prod Adj. 205-d WW Pregnancy rate % 1995 93 6.7 240 97 1996 86 4.8 211 98 1997 101 6.1 232 81 1998 97 5.2 220 59 1999 63 7.5 229 93 2000 107 5.6 160 80 2001 121 6.4 194 86 Average 95 6.0 212 84 New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center Year d to first estrus 24-h milk prod kg Adj. 205-d WW,kg Pregnancy rate % 2003 58 7.6 241 96 2004 77 8.5 241 95 2005 70 -- 219 89 2006 70 5.6 159 94 2007 81 6.4 220 96 Avg 71 7.1 217 94 233 New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center • Before 2003 (7 years); – 95 days to first estrus – 84% pregnant – Weaning wt. 218 kg ( minus drought yr) • After 2003 (5 years): – 71 days to first estrus – 94% pregnant – Weaning wt. 233 kg ( minus drought yr) New Mexico State University Nutrient Partitioning • Regulated by changing tissue sensitivity to insulin – Insulin facilitates glucose uptake into tissues • Cow naturally alters insulin sensitivity prepostpartum – Growth hormone antagonistic to insulin New Mexico State University Nutrient Partitioning • Regulated by changing tissue sensitivity to insulin • Diet quality • Lactation New Mexico State University Measurements – Insulin Sensitivity • Intravenous glucose tolerance test (GTT) – 53 d postpartum – Subsample of cows (n = 46) – Day after supplementation • Glucose half-life – Time required for 50% decrease in peak serum glucose concentration New Mexico State University Example GTT Curves Glucose (mg/dl) 270 220 170 Half concentration 120 70 -10 10 30 50 70 90 110 130 150 170 Min (relative to infusion) New Mexico State University Lactation Influences Insulin Sensitivity • Compared cows that calved to cows that calved and lost their calves – 55 days postpartum – Lactating cows more insulin sensitive than nonlactating counterparts – 53 vs 100 ± 12 min glucose half-life New Mexico State University Diet Quality Influences Insulin Sensitivity • Drier spring and wetter summer – Improved diet quality from spring to summer – 87 vs 45 ± 6 min glucose half-life New Mexico et State University Endecott al., 2003, 2004 Diet Quality Influences Insulin Sensitivity • Increased diet quality spring to summer – 87 vs 45 ± 6 min glucose half-life – or • Wetter spring drier summer – Decreased diet quality spring to summer – 58 vs 94 ± 12 min glucose half-life New Mexico et State University Endecott al., 2003, 2004 Insulin Sensitivity May Influence Reproduction • If insulin resistance results in poor tissue uptake of nutrients then, – creates poor animal performance New Mexico State University 2000 1800 1600 Breeding Dec Nov Oct Sep Aug Jul Jun May Apr Mar Weaning Feb 1400 1200 1000 800 600 400 200 0 Calving Jan Glucose Need (g/d) Cow Glucose Demand Versus Production Cycle Month New Mexico State University EXAMPLE UNDERNUTRITIONlactating range beef cow • Cow’s daily glucose 610g lactose 462g fat (58g glycerol) daily catabolism • Glucose carbon 257 g 23 g 176 g 456 g C (1140 g) • Cow glucose sources 34g N urine (213g prot) 360g (900g glucose-from propionate?) 96 g 360 g 456 g New Mexico State University UNDERNUTRITION • What are responses to declining glucose? – Glucagon stimulates glycogenolysis, gluconeogenesis from AA etc. – glucocorticoids initiate mobilization of protein and lipids – growth hormone promotes AA uptake – insulin concentration drops New Mexico State University STRATEGIES to alleviate metabolic limitations • Supply glucogenic precursors – grain (shift ruminal VFA production) – bypass (UIP) protein (glucogenic amino acids) – ionophores – propionate • Supply hormones – insulin New Mexico State University STRATEGIES to alleviate metabolic limitations LH hypothalmus + FSH + ovary insulin + + glucose fat + OVULATION body condition nutrition trend protein tissue insulin, LGF1 glucose GNRH growth hormone anterior pituitary New Mexico State University - Rumen Fermentation of Carbohydrates Cellulose Hemicellulose Pectin Starch Sugars GLUCOSE Volatile Fatty Acids Acetate, Propionate, Butyrate New Mexico State University Metabolic Fate of Volatile Fatty Acids Acetate Propionate Butyrate energy source for tissues liver for glucose production energy source for rumen wall New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) Glycolysis Phosphoenolpyruvate Pyruvate In cell New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) Glycolysis Phosphoenolpyruvate Pyruvate In cell Acetyl CoA Oxaloacetate New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) Phosphoenolpyruvate Ruminal acetate Pyruvate & FAs In cell Acetyl CoA Oxaloacetate New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) Phosphoenolpyruvate Ruminal acetate Pyruvate & In cell Acetyl CoA Oxaloacetate TCA Cycle Succinyl CoA Citrate ATP New Mexico State University FAs Glucose and Acetate Metabolism Ruminal acetate & FAs Glucose Phosphoenolpyruvate Pyruvate Acetyl CoA Oxaloacetate TCA Cycle Succinyl CoA Citrate KETONES ATP New Mexico State University PROPOSED CAUSE OF INSULIN RESISTANCE IN RANGE COWS STIMULATION OF GLUCOSE TRANSPORT INSULIN Fatty acids Glut-4 INSULIN RECEPTOR B-hydroxy Butyrate PROTEIN KINASE B Insulin responsive Glut-4 containing vesicle Fatty acids PHOSPHORYLATION IRS PI-3 dependent Phosphoinositide-3 Kinase New Mexico State University Glucose and Acetate Metabolism Ruminal acetate & FAs Glucose Phosphoenolpyruvate Pyruvate Acetyl CoA Oxaloacetate TCA Cycle Succinyl CoA Citrate KETONES ATP New Mexico State University Effect of Supplement on Acetate Tolerance Test 40 35 35 29 Acetate half-life (min) 30 27 25 20 15 10 5 0 0 40 80 New Mexico State University Effects of Supplement on Blood Ketone Concentrations 0.45 0.4 0.38 0.35 0.29 0.3 0.3 0.25 0.2 0.15 0.1 0.05 0 0 40 80 New Mexico State University Insulin Sensitivity May Influence Reproduction • Supplements enhance acetate oxidation • glucose precursors to provide oxaloacetate • Then amelioration of insulin resistance from supplementation of glucose precursors could result in improved reproductive performance New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center • Before 2003 (7 years); – 95 days to first estrus – 84% pregnant – Weaning wt. 218 kg ( minus drought yr) • After 2003 (5 years): – 71 days to first estrus – 94% pregnant – Weaning wt. 233 kg ( minus drought yr) New Mexico State University New Mexico State University