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New Mexico State University

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New Mexico State University

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. M.K. Petersen, S. Cox, D. Hawkins, C. LLööest, S. Soto, S. Ivey, T. Mulliniks, R. est, S. Soto, S. Ivey, T. Mulliniks, R. Endecott, R. Waterman and J. SawyerEndecott, 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

WWPregnancy

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

AveragAveragee

9595 6.06.0 212212 8484

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

kgAdj. 205-d

WW,kgPregnancy

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 94233

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

70

120

170

220

270

-10 10 30 50 70 90 110 130 150 170

Glu

cose

(m

g/d

l)

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

0

200

400

600

800

1000

1200

1400

1600

1800

2000

Jan

Feb

Mar

Apr

May

Jun

Jul

Aug

Sep

Oct

Nov

DecGlu

cose

Need

(g

/d)

Month

Calving

Breeding

Weaning

New Mexico State University

EXAMPLE UNDERNUTRITION-lactating range beef cow

• Cow’s daily glucose610g lactose

462g fat (58g glycerol)

daily catabolism

• Cow glucose sources34g 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

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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

ovaryovary

hypothalmushypothalmus

anterioranteriorpituitarypituitary

body conditionbody conditionnutrition trendnutrition trendprotein tissueprotein tissueinsulin, LGF1insulin, LGF1glucoseglucose

++GNRHGNRH

++

LHLH

FSHFSH++

++

insuliinsulinnglucosglucoseefatfat

++

OVULATIONOVULATION

growthgrowthhormonehormone

--

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Acetate, Propionate, ButyrateVolatile Fatty Acids

GLUCOSE

SugarsStarchPectinHemicelluloseCellulose

Rumen Fermentation of Carbohydrates

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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)

GlycolysisPhosphoenolpyruvate Pyruvate

In cell

New Mexico State University

Glucose and Acetate Metabolism

Glucose (from liver via blood)

GlycolysisPhosphoenolpyruvate Pyruvate

OxaloacetateAcetyl CoA

In cell

New Mexico State University

Glucose and Acetate Metabolism

Glucose (from liver via blood)

Phosphoenolpyruvate Pyruvate

OxaloacetateAcetyl CoA

Ruminal acetate & FAs

In cell

New Mexico State University

Glucose and Acetate Metabolism

Glucose (from liver via blood)

Phosphoenolpyruvate Pyruvate

OxaloacetateAcetyl CoA

Ruminal acetate & FAs

TCA CycleCitrate

Succinyl CoA ATP

In cell

New Mexico State University

Glucose and Acetate Metabolism

Phosphoenolpyruvate Pyruvate

OxaloacetateAcetyl CoA

TCA CycleCitrate

Succinyl CoA ATP

Glucose Ruminal acetate & FAs

KETONES

New Mexico State University

PROPOSED CAUSE OF INSULIN RESISTANCE IN RANGE COWS

INSULININSULIN

INSULINRECEPTOR

IRS

PHOSPHORYLATION

Phosphoinositide-3Kinase

PI-3 dependentPI-3 dependent

Glut-4

STIMULATION OF STIMULATION OF GLUCOSE TRANSPORTGLUCOSE TRANSPORT

PROTEINPROTEINKINASEKINASE

BB

Insulin responsiveGlut-4 containingvesicle

B-hydroxyB-hydroxy

ButyrateButyrate Fatty Fatty acidsacids

Fatty acids

New Mexico State University

Glucose and Acetate Metabolism

Phosphoenolpyruvate Pyruvate

OxaloacetateAcetyl CoA

TCA CycleCitrate

Succinyl CoA ATP

Glucose Ruminal acetate & FAs

KETONES

New Mexico State University

35

2927

0

5

10

15

20

25

30

35

40

Ace

tate

ha

lf-l

ife

(min

)

0 40 80

Effect of Supplement on Acetate Tolerance Test

New Mexico State University

0.38

0.29 0.3

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0 40 80

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