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

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 Yeard to first estrus24-h milk prod kgAdj. 205-d WW, kg Pregnancy rate %

New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center Yeard to first estrus24-h milk prodAdj. 205-d WW Pregnancy rate % Average

New Mexico State University Comparison of reproductive performance, milk production, and weaning weight for young range cows at Corona Range & Livestock Research Center Yeard to first estrus24-h milk prod kg Adj. 205-d WW,kg Pregnancy rate % Avg

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 pre- postpartum –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) Min (relative to infusion) Half concentration

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 non- lactating 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 Endecott et al., 2003, 2004

New Mexico State University 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 Endecott et al., 2003, 2004

New Mexico State University Insulin Sensitivity May Influence Reproduction If insulin resistance results in poor tissue uptake of nutrients then, –creates poor animal performance

New Mexico State University Cow Glucose Demand Versus Production Cycle Glucose Need (g/d) Month Calving Breeding Weaning

New Mexico State University EXAMPLE UNDERNUTRITION- lactating range beef cow Cow’s daily glucose 610g lactose 462g fat (58g glycerol) daily catabolism Cow glucose sources 34g N urine (213g prot) 360g (900g glucose-from propionate?) Glucose carbon 257 g 23 g 176 g 456 g C (1140 g) 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 ovary ovary hypothalmus anteriorpituitary body condition nutrition trend protein tissue insulin, LGF1 glucose + GNRH + LH FSH + + insulinglucosefat + OVULATION growthhormone -

New Mexico State University Acetate, Propionate, Butyrate Volatile Fatty Acids GLUCOSE SugarsStarchPectinHemicelluloseCellulose Rumen Fermentation of Carbohydrates

New Mexico State University Metabolic Fate of Volatile Fatty Acids Acetate energy source for tissues Propionate liver for glucose production Butyrate energy source for rumen wall

New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) Glycolysis PhosphoenolpyruvatePyruvate In cell

New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) Glycolysis PhosphoenolpyruvatePyruvate Oxaloacetate Acetyl CoA In cell

New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) PhosphoenolpyruvatePyruvate Oxaloacetate Acetyl CoA Ruminal acetate & FAs In cell

New Mexico State University Glucose and Acetate Metabolism Glucose (from liver via blood) PhosphoenolpyruvatePyruvate Oxaloacetate Acetyl CoA Ruminal acetate & FAs TCA Cycle Citrate Succinyl CoA ATP In cell

New Mexico State University Glucose and Acetate Metabolism PhosphoenolpyruvatePyruvate Oxaloacetate Acetyl CoA TCA Cycle Citrate Succinyl CoA ATP Glucose Ruminal acetate & FAs KETONES

New Mexico State University PROPOSED CAUSE OF INSULIN RESISTANCE IN RANGE COWS INSULIN INSULIN RECEPTOR IRS PHOSPHORYLATION Phosphoinositide-3 Kinase PI-3 dependent Glut-4 STIMULATION OF GLUCOSE TRANSPORT PROTEINKINASEB Insulin responsive Glut-4 containing vesicle B-hydroxyButyrate Fattyacids Fatty acids

New Mexico State University Glucose and Acetate Metabolism PhosphoenolpyruvatePyruvate Oxaloacetate Acetyl CoA TCA Cycle Citrate Succinyl CoA ATP Glucose Ruminal acetate & FAs KETONES

New Mexico State University Effect of Supplement on Acetate Tolerance Test

New Mexico State University Effects of Supplement on Blood Ketone Concentrations

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