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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