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Department of Animal Science, Michigan State University, East Lansing, MI 48824 * Dairy and Swine R & D Center, Agriculture and Agri-Food Canada, Lennoxville, QC, Canada, J1M 1Z3
4To whom correspondence and reprint requests should be addressed.
| ABSTRACT |
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KEY WORDS: chromium glucose insulin C-peptide pigs
| INTRODUCTION |
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High Cr yeast contains a glucose tolerance factor (Mertz 1976
). Although the chemical composition and structure of the
glucose tolerance factor have not been identified completely, it is
considered to be a trivalent Cr nicotinic acid complex (Mertz 1993
, Mowat 1997
, NRC 1997
). High
Cr yeast supplementation (9 g Brewers yeast/d) improved glucose
tolerance in elderly subjects (Offenbacher and Pi-Sunyer 1980
), but this effect of high Cr yeast supplementation (160
µg Cr/d) was not repeated in elderly subjects with stable
impaired glucose tolerance (Uusitupa et al. 1992
).
Meanwhile, Cr picolinate (200 µg Cr/kg diet) increased
glucose clearance rate in pigs after an intravenous glucose tolerance
test (i.v.
GTT)5
(Amoikon et al. 1995
). Chromium (5 mg/kg) as
CrCl3 provided in the drinking water improved
insulin response to an i.v. GTT in rats with impaired glucose tolerance
due to dietary Cr deficiency (Striffler et al. 1995
).
High Cr yeast did not affect either plasma insulin or plasma
C-peptide response in elderly subjects (Uusitupa et al. 1992
). The inconsistent effects of dietary Cr supplementation
on glucose tolerance and insulin response may result from uncontrolled
factors, such as nutritional, metabolic and stress status.
Peripheral plasma insulin concentration does not precisely reflect
insulin secretion per se, although it has been used to indicate insulin
secretion in most Cr studies. Insulin and C-peptide are secreted in
equimolar amounts (Rubenstein et al. 1969
); however,
insulin, unlike C-peptide, is extracted from the portal blood by
the liver. Plasma C-peptide, with negligible hepatic extraction and
constant peripheral clearance, is considered to be a more reliable
indicator of insulin secretion than peripheral insulin concentration
(Polonsky et al. 1983
). Insulin secretion and hepatic
extraction can be estimated accurately from plasma C-peptide levels
by an appropriate compartmental modeling during an i.v. GTT
(Cobelli and Pacini 1988
, Polonsky et al. 1986
, Polonsky and Rubenstein 1984
, Van Cauter et al. 1992
, Watanabe et al. 1998
).
Chromium may affect the hepatic extraction of insulin from the portal
blood because chromium tripicolinate was shown to reduce
insulin-binding percentage by porcine hepatic plasma membranes
(Ward et al. 1994
). Increased peripheral insulin
concentration may increase glucose uptake by skeletal muscle and
adipose tissue. Improvement in glucose tolerance may benefit the
utilization of glucose and improve the long-term efficiency of
growth in pigs. The objective of this study was to evaluate the effects
of supplemental Cr from high Cr yeast on glucose tolerance and insulin
response in growing pigs.
| MATERIALS AND METHODS |
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Michigan State University All University Committee on Animal Use and Care approved the handling and blood sampling of pigs used in this experiment, and all animals were treated in an ethical manner. Twenty Landrace x Yorkshire barrows and gilts with an average initial body weight of 47.9 ± 2.9 kg were randomly assigned to one of two treatment diets with two pens each. Each pen, with a size of 15 m2 (2.74 m x 5.48 m), contained five pigs assigned on the basis of sex and body weight.
Pigs were fed a corn-soybean meal basal diet (Table 1
) formulated to exceed nutrient requirements for swine (NRC
1988
). The basal diet contained the following: Cr, 204
µg/kg; crude protein, 141 g/kg; lysine, 6.8 g/kg; and
metabolic energy, 13.78 kJ/kg. The dietary treatments consisted of the
basal diet supplemented with either 0 (C) or an additional 200
µg Cr/kg of diet (CR) from high Cr yeast (Lallemand
Distribution, Ontario, Canada). Pigs had ad libitum access to the
experimental diets for a minimum of 23 d and a maximum of 30 d. Growth performance and food intake were measured weekly and daily,
respectively. Average daily body weight gain (ADG) and average daily
food intake (ADFI) were not affected (P > 0.10) by
high Cr yeast supplementation during the 21-d feeding period
(Table 2
).
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Duplicate samples of the basal diet were ground by a Wiley hammer mill
(Thomas Scientific, Philadelphia, PA) with steel blades and
passed through a 1-mm brass screen. The samples were digested by the
nitric acid method (AOAC 1990
). Chromium concentration
in the digesta was determined using the Spectroflame ICP unit (Spectro,
Littleton, MA) by the inductively coupled plasma method (Eaton et al. 1995
). The intra- and interassay CV for this method were
7.6 and 4.6%, respectively. The Cr concentration in the basal diet was
204 µg/kg diet (as fed basis).
Cannulation.
A total of 12 pigs were selected for the glucose tolerance test from
the initial group of 20 pigs. This was done to ensure a precise
selection for the glucose tolerance test on the basis of equal body
weight and an ideal body condition index, thus minimizing variation
among individual pigs. On d 23 and 30, six barrows (C, n
= 3; CR, n = 3) and six gilts (C,
n = 3; CR, n = 3) were selected
on the basis of similar body weight and were fitted surgically with a
catheter in a jugular vein according to the method of Trottier (1995)
. Cannulated pigs were penned individually. Individual
pen size was 0.56 m2 (0.53 m x 1.06 m). Pigs
were fed an amount approximating their presurgical ad libitum intake.
Glucose challenges.
On d 4 postsurgery, an i.v.GTT was conducted after overnight food deprivation. Blood samples were obtained before the i.v. GTT to evaluate basal values of plasma glucose, insulin and C-peptide. Dextrose (500 g/L) was infused through the jugular vein catheter at a dose of 0.5 g/kg of body weight with an infusion rate of 10 g glucose/min within 6 min. Blood samples (10 mL) were collected at -6, -4, -2 and 0 min relative to the completion of dextrose infusion, and 5, 10, 15, 20, 30, 45, 60 and 90 min postinfusion.
Blood samples were collected into EDTA-coated monovettes and immediately placed on ice. Blood samples were centrifuged at 1500 x g for 15 min at 4°C within 30 min of collection to separate plasma. Plasma was stored at -80°C until analyzed for glucose, insulin and C-peptide.
Assays.
Plasma concentrations of glucose were determined in triplicate using a commercial kit (Sigma Procedure No. 315, St. Louis, MO) and read at 505 nm using a BU 7400 spectrophotometer (Beckman Instruments, Fullerton, CA). Plasma concentrations of insulin were assayed in triplicate using a commercial porcine insulin RIA kit (Linco Cat. No. PI-12K, St. Louis, MO) and quantified using a 1290 Gamma Trac (Tm Analytic, Tampa, FL). Plasma concentrations of C-peptide were assayed in duplicate using a commercial porcine C-peptide RIA kit (Linco Cat. No. PCP-20K) and counted using a Wallac Wizard counter (Fisher Scientific, Pittsburgh, PA); the intra- and interassay CV were 2.4 and 2.8%, respectively.
Plasma kinetics of glucose, insulin, and C-peptide.
The natural logarithm was calculated for plasma concentrations of
glucose, insulin or C-peptide at all time points. Time of sampling
from 0 to 20 min for glucose, or from 5 to 30 min for both insulin and
C-peptide, was regressed against the natural logarithm of their
corresponding plasma concentrations for each individual pig. The slope
of the regression line was considered the plasma clearance rate of
glucose [k, µmol/(L · min)],
insulin [k, fmol/(L · min)] and C-peptide
[k, fmol/(L · min)] (Kaneko 1997
).
Their plasma half-lives (T1/2, min) were calculated
using the constant -0.693 divided by the respective slopes
(loge 0.5 = k · T1/2,
where T1/2 = -0.693/k). Areas of
plasma concentrations of glucose, insulin or C-peptide within 30
min postinfusion were integrated for each individual pig.
Statistical analyses.
Data from the experiment were analyzed by the Mixed Procedure with a repeated statement of SAS/STAT (Version 6.12, SAS Institute, Cary, NC). The first-order autoregressive was assumed in covariance structure. Individual pig was considered the experimental unit in the analysis of ADG, plasma concentrations and plasma kinetics of glucose, insulin and C-peptide. Pen was used as the experiment unit in the analysis of ADFI. The model for plasma concentrations of glucose, insulin and C-peptide included treatment, sex, time, and all two-way and three-way interactions with time in a repeated statement. For ADG, ADFI, k, T1/2, 30-min area and basal plasma value, the model included only treatment. Least-squares means are presented; differences are considered significant at P < 0.05 and tending toward significance at P < 0.10.
| RESULTS |
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Basal plasma glucose concentrations, i.e., the values of plasma glucose
in pigs deprived of food overnight, were not different between
treatments (P > 0.05; Table 3
). High Cr yeast supplementation tended to decrease the 30-min area of
plasma glucose concentration (P < 0.10) (Table 3)
and
the 90-min overall mean of plasma glucose concentrations after an i.v.
GTT (P < 0.10; C vs. CR: 8.4 ± 0.2 vs. 7.9
± 0.2 mmol/L). The response curve of plasma glucose concentration
against sampling time after an i.v. GTT is shown in Figure 1
. Plasma glucose concentrations were lower (P < 0.01)
in pigs fed CR at postinfusion times 5, 10, 15 and 20 min. Effects of
high Cr yeast supplementation on plasma glucose kinetics are shown in
Table 4
. Glucose clearance rate tended to be higher (P < 0.10)
and glucose clearance half-life was lower (P < 0.05) in pigs fed CR. Therefore, high Cr yeast supplementation improved
glucose tolerance in pigs, but it did not cause hypoglycemia.
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Basal plasma insulin concentration, i.e., the value of plasma insulin
in pigs deprived of food overnight, tended to be higher in pigs fed CR
than in those fed C (P < 0.10) (Table 3)
. High Cr
yeast supplementation did not affect the 30-min area of plasma insulin
concentration (Table 3)
or the 90-min overall mean of plasma insulin
concentrations after an i.v. GTT (C vs. CR: 216.9 ± 24.5 vs.
254.9 ± 24.5 pmol/L). The response curve of plasma insulin
concentrations against time after an i.v. GTT is shown in Figure 2
. Plasma insulin concentrations were higher in pigs fed CR at 2 and 0
min before the completion of dextrose infusion (P < 0.05) and tended to be higher at 5 min postinfusion (P
< 0.10). Effects of high Cr yeast supplementation on plasma
insulin kinetics are shown in Table 4
. Plasma insulin clearance rate
was higher (P < 0.05) and insulin clearance
half-life lower (P < 0.05) in pigs fed CR.
Therefore, high Cr yeast supplementation positively altered plasma
insulin kinetics after an i.v. GTT.
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Basal plasma C-peptide concentrations, i.e., the values of plasma
C-peptide in pigs deprived of food overnight, were not different
between treatments (Table 3)
. High Cr yeast supplementation did not
affect the 30-min area of plasma C-peptide (Table 3)
or the 90-min
overall mean of plasma C-peptide concentrations after an i.v. GTT
(C vs. CR: 354.3 ± 33.3 vs. 368.8 ± 33.3 pmol/L). The
response curve of plasma C-peptide concentrations against time
after an i.v. GTT is shown in Figure 3
. There was no difference in plasma C-peptide concentration at any
sampling time between treatments. Effects of high Cr yeast
supplementation on plasma C-peptide kinetics are shown in Table 4
.
Plasma C-peptide clearance rate was higher (P < 0.05) and C-peptide clearance half-life lower (P
< 0.05) in pigs fed CR. Therefore, high Cr yeast supplementation
did not affect C-peptide secretion, although it positively altered
plasma C-peptide kinetics after an i.v. GTT.
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| DISCUSSION |
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This study shows that high Cr yeast supplementation tended to increase
basal plasma insulin concentration in pigs. Similarly, an elevation in
serum insulin concentration was found in pigs supplemented with 200
µg Cr/kg of diet as Cr tripicolinate (Crow et al. 1997
, Lien et al. 1996
), and in rats provided
with CrCl3-containing drinking water for 12 wk
(Striffler et al. 1995
). No change in basal plasma
insulin concentration was observed in pigs fed Cr tripicolinate
(Min et al. 1997
, Page et al. 1993
), in
rats provided with CrCl3-containing drinking
water for 24 wk (Striffler et al. 1995
) or in healthy
human subjects supplemented with Cr nicotinate (Wilson and Gondy 1995
). On the contrary, basal plasma insulin concentration
decreased in pigs supplemented with Cr tripicolinate (Amoikon et al. 1995
, Evock-Clover et al. 1993
). Dietary Cr
tripicolinate apparently accentuated the increase in basal plasma
insulin concentration in uncrowded pigs, in which dietary lysine level
was increased from 80 to 120% of the NRC recommended lysine
requirement (Ward et al. 1997
). The inconsistency of
plasma insulin response to Cr supplementation in the literature may be
attributed by the Cr source, the nutritional status of the animal or
the subject, and the environmental conditions, therefore rendering
comparisons difficult to make. Dietary Cr from organic complexes, such
as Cr tripicolinate, Cr nicotinate and high Cr yeast, is absorbed more
efficiently than is Cr from inorganic CrCl3
(NRC 1997
). The bioavailability of Cr contained in food
ingredients has not been defined clearly. Steers supplemented with the
same amount of supplemental Cr (400 µg/kg dry matter) as
Cr nicotinic acid apparently had a faster rate of plasma glucose
clearance and higher serum insulin concentrations after an i.v. GTT
compared with high Cr yeast or CrCl3
(Kegley and Spears 1995
). However, it is not known
whether this effect on glucose metabolism is due to differences in Cr
bioavailability or to specific chemical forms of dietary Cr required
per se. Biologically active forms of Cr in the body may be the glucose
tolerance factor (Schwarz and Mertz 1957
) and/or the
low-molecular-weight Cr-binding substances (Davis and Vincent 1997b
, Yamamoto et al. 1988
).
In any case, peripheral plasma insulin concentration may not represent
insulin secretion accurately at the level of the ß-cell because of
significant hepatic extraction of insulin by the liver (Polonsky et al. 1983
). Furthermore, changes in hepatic insulin
extraction violate the reliability of the use of peripheral insulin
concentration as a measure of prehepatic insulin secretion
(Bonora et al. 1983
). The evidence that C-peptide is
secreted from the ß-cell in equimolar amount with insulin, but not
extracted by the liver to any substantial degree, has provided a solid
physiologic basis for the use of peripheral C-peptide concentration
as an indicator of prehaptic insulin secretion (Polonsky et al. 1983
, Polonsky and Rubenstein 1984
). Peripheral
plasma insulin concentration reflects a balance between insulin
secretion per se and hepatic extraction of insulin (Morgan 1992
). No difference in basal plasma C-peptide values was
found in pigs between treatments, possibly indicating that high Cr
yeast supplementation may not affect insulin secretion. The 30-min
areas of either plasma insulin or plasma C-peptide concentrations
were not different between treatments, thus further indicating that
high Cr yeast supplementation did not affect insulin secretion after an
i.v. GTT.
Increased peripheral plasma insulin concentration is possibly due to a
reduced hepatic extraction of insulin from the portal blood in pigs
supplemented with high Cr yeast. Increased plasma insulin concentration
at 2 and 0 min before the completion of dextrose infusion and at 5 min
postinfusion was not accompanied by a comparable increase in plasma
C-peptide concentration, indicating that the higher plasma insulin
concentrations at its early response after an i.v. GTT were possibly
due to a decreased hepatic extraction of insulin rather than increased
insulin secretion per se. Ward et al. (1994)
showed that
insulin binding percentage was lower in liver cell plasma membranes
from pigs supplemented with 200 µg Cr/kg of diet as Cr
tripicolinate. Reduced insulin binding in hepatic cell plasma membranes
by Cr tripicolinate may decrease hepatic extraction of insulin from the
portal blood, which may result in an increase in peripheral plasma
insulin concentration. With a kinetic characteristic of high
Km value, glucose transporter-2 is the
major glucose transporter isoform expressed in hepatocytes and is not
mediated by insulin (Devaskar and Mueckler 1992
). Thus,
glucose uptake by the liver may not be affected by reduced insulin
binding. In contrast, increased peripheral plasma insulin may stimulate
glucose uptake by skeletal muscle and adipose tissue because glucose
transporter-4 in these tissues is sensitive to insulin. Therefore, the
clearance rate of plasma glucose after an i.v. GTT could be increased
in pigs supplemented with high Cr yeast. The relationship between
insulin concentration and glucose clearance rate is assumed to be
approximately linear within the physiologic range of insulin
concentrations. Insulin stimulates glucose uptake in the
insulin-sensitive tissues in which glucose clearance tends to
saturate at supraphysiologic insulin level (Mari 1998
).
Therefore, an increase (48.1%, although not significant) in the basal
insulin concentration in pigs supplemented with high Cr yeast may
contribute physiologically to an increase in glucose clearance rate in
the pigs. The ratio of glucose clearance rate to 30-min C-peptide
concentration area may indicate peripheral insulin sensitivity provided
that 30-min C-peptide concentration area reflects prehepatic
insulin secretion in an accurate manner. This ratio in pigs
supplemented with high Cr yeast increased by 35.6% compared with that
in unsupplemented pigs (220.7 vs. 162.6, respectively), probably
indicating an improvement in peripheral insulin sensitivity in pigs
supplemented with high Cr yeast.
The effect of high Cr yeast supplementation on plasma insulin
concentrations after an i.v. GTT occurred earlier than that on plasma
glucose concentrations. In pigs supplemented with high Cr yeast, plasma
insulin concentrations seemed to increase within 5 min postinfusion,
but plasma glucose concentrations started to decrease at 5 min
postinfusion. This clearly indicates that improved glucose tolerance is
resulting from increased insulin action in pigs by high Cr
supplementation. Insulin induces the translocation of glucose
transporter-4 from its intracellular storage sites to the cellular
surface, resulting in augmented glucose transport in skeletal muscle
and adipose tissue. This effect occurs within minutes and is rapidly
reversible upon insulin withdrawal (Devaskar and Mueckler 1992
). Although plasma insulin concentrations in pigs
supplemented with high Cr yeast increased at early response to i.v.
GTT, the clearance rate of plasma insulin also increased at late
response, i.e., from 5 to 30 min postinfusion. As discussed above, the
increased peripheral plasma insulin concentration at early response can
stimulate glucose uptake by insulin-sensitive tissues and reach a
more rapid onset of reactive hypoglycemia. The increased clearance rate
of plasma insulin at late response can slow down glucose uptake by
insulin-sensitive tissues and avoid a long-term duration of
reactive hypoglycemia. It can also quickly relieve reactive
hyperinsulinemia after the reactive hypoglycemia occurs in pigs.
Therefore, possibly through a decreased hepatic extraction of insulin
from the portal blood, temporally higher effective insulin
concentrations as early response to i.v. GTT can enhance cellular
glucose uptake in skeletal muscle and adipose tissue (Ward et al. 1994
), leading to improved glucose tolerance in pigs
supplemented with high Cr yeast.
C-peptide (administered at a physiologic dose) augments glucose
utilization in type 1 diabetes patients (Johansson et al. 1992
). C-peptide stimulates glucose transporter in skeletal
muscle independently of insulin receptor and tyrosine kinase activation
(Zierath et al. 1996
). C-peptide may inhibit
glucose-induced insulin release (Leclercq-Meyer et al. 1997
, Wojcikowski et al. 1983
). These findings
indicate that C-peptide is itself a biologically active hormone
(Wahren and Johansson 1998
). Although the physiologic
importance of changes in plasma kinetics of C-peptide is not known
at the moment, we speculate that an increase in the clearance rate of
plasma C-peptide in pigs supplemented with high Cr yeast may
relieve C-peptides inhibition of glucose-induced insulin
secretion and favor a short-term duration of the reactive
hypoglycemia during an i.v. GTT.
The present finding indicates that high Cr yeast supplementation
improves whole-body glucose utilization. Glucose utilization is
related positively to growth rate in rats (Holness 1996
). Skeletal growth retardation in type 1 diabetes is
associated with reduced expression of glucose transporter-4 and
insulin-like growth factor-1 receptor in the bone growth center,
resulting in an impairment in glucose utilization (Maor and Karnieli 1999
). It is speculated that high Cr yeast
supplementation in pigs may also affect glucose utilization in the long
term and improve growth. The dietary Cr requirement of swine has not
been established to date, although improvement in growth rate was
reported mainly in pigs supplemented with 200500 µg
Cr/kg as Cr tripicolinate in a corn-soybean basal diet (NRC
1997
). However, appropriate supplemental Cr levels in diets
depend on the nutritional status of Cr in the body, the degree of
glucose intolerance and/or stress, the bioavailable amount of Cr
contained in food and supplemental chemicals, and the type of diet
(Anderson 1998
, NRC 1997
).
In summary, high Cr yeast supplementation improved glucose tolerance in pigs as indicated by increased glucose clearance rate and decreased glucose half-life. High Cr yeast supplementation increased the ratio of glucose clearance rate to 30-min C-peptide concentration area, probably indicating an improvement in peripheral insulin sensitivity in pigs. High Cr yeast supplementation might not affect insulin secretion per se as indicated by plasma C-peptide concentrations, but possibly decreased hepatic extraction of insulin and led to higher effective concentrations of plasma insulin at early response to an i.v. GTT for stimulating glucose uptake in target tissues.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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2 Supported by Michigan State University
Agricultural Experiment Station and JEFO Inc. (Quebec, Canada). ![]()
3 Current address: Department of Animal Science,
University of Illinois at Urbana-Champaign, Urbana, IL 61801. ![]()
5 Abbreviations used: ADFI, average daily food
intake; ADG, average daily body weight gain; C, unsupplemented control
diet; CR, high chromium yeastsupplemented diet; i.v.GTT, intravenous
glucose tolerance test; k, plasma clearance rate;
T1/2, half-life. ![]()
Manuscript received October 25, 1999. Initial review completed November 15, 1999. Revision accepted February 10, 2000.
| REFERENCES |
|---|
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1. Amoikon E. K., Fernandez J. M., Southern L. L., Thompson D. L., Jr, Ward T. L., Olcott B. M. Effect of chromium tripicolinate on growth, glucose tolerance, insulin sensitivity, plasma metabolites, and growth hormone in pigs. J. Anim. Sci. 1995;73:1123-1130[Abstract]
2.
Anderson R. A. Chromium, glucose intolerance and diabetes. J. Am. Coll. Nutr. 1998;17:548-555
3. Association of Official Analytical Chemists Official Methods of Analysis 15th ed. 1990:324-325 AOAC Arlington, VA.
4. Bonora E., Zavaroni I., Coscelli C., Butturini U. Decreased hepatic extraction in subjects with mild glucose intolerance. Metabolism 1983;32:438-446[Medline]
5. Cobelli C., Pacini G. Insulin secretion and hepatic extraction in humans by minimal modeling of C-peptide and insulin kinetics. Diabetes 1988;37:223-231[Abstract]
6. Crow S. D., Newcomb M. D., Ruth P. Effect of dietary chromium addition on growth performance and carcass characteristics of growing and finishing pigs. J. Anim. Sci. 1997;75(suppl. 1):79(abs.)
7.
Czech M. P., Corvera S. Signaling mechanisms that regulate glucose transport. J. Biol. Chem. 1999;274:1865-1868
8. Davis C. M., Vincent J. B. Chromium oligopeptide activates insulin receptor tyrosine kinase activity. Biochemistry 1997a;36:4382-4385[Medline]
9. Davis C. M., Vincent J. B. Isolation and characterization of a biologically active chromium oligopeptide from bovine liver. Arch. Biochem. Biophys. 1997b;339:335-343[Medline]
10. Devaskar S. U., Mueckler M. M. The mammalian glucose transporters. Pediatr. Res. 1992;31:1-13[Medline]
11. Eaton A. D., Clesceri L. S., Greenberg A. E. Standard Methods for the Examination of Water and Wastewater 19th ed. 1995:34-39 American Public Health Association Washington, DC.
12. Evock-Clover C. M., Polanssky M. M., Anderson R. A., Steele N. C. Dietary chromium supplementation with or without somatotropin treatment alters serum hormones and metabolites in growing pigs without affecting growth performance. J. Nutr. 1993;123:1504-1512
13.
Holness M. J. Impact of early retardation on glucoregulatory control and insulin action in mature rats. Am. J. Physiol. 1996;270:E946-E954
14. Johansson B. L., Sjoberg S., Wahren J. The influence of human C-peptide on renal function and glucose utilization in type 1 (insulin-dependent) diabetic patients. Diabetologia 1992;35:121-128[Medline]
15. Kaneko J. J. Carbohydrate metabolism and its diseases. Kaneko J. J. Harvey J. W. Bruss M. L. eds. Clinical Biochemistry of Domestic Animals 1997:65-67 Academic Press New York, NY.
16. Kegley E. B., Spears J. W. Immune response, glucose metabolism, and performance of stressed feeder calves fed inorganic or organic chromium. J. Anim. Sci. 1995;73:2721-2726[Abstract]
17. Leclercq-Meyer V., Malaisse W. J., Johansson B. L., Wahren J. Effect of C-peptide on insulin and glucagon release by isolated perfused rat pancreas. Diabetes Metab. 1997;23:149-154[Medline]
18. Lien T. F., Chen S. Y., Wu C. P., Chen C. L., Hu C. Y. Effects of chromium picolinate and chromium chloride on growth performance and serum traits of growing-finishing swine. J. Anim. Sci. 1996;74(suppl. 1):185(abs.)
19.
Maor G., Karnieli E. The insulin-sensitive glucose transporter (GLUT4) is involved in early bone growth in control and diabetic mice, but is regulated through the insulin-like growth factor I receptor. Endocrinology 1999;140:1841-1851
20. Mari A. Assessment of insulin sensitivity and secretion with the labelled intravenous glucose tolerance test: improved modelling analysis. Diabetologia 1998;41:1029-1039[Medline]
21. Mertz W. Effects and metabolism of glucose tolerance factor. Present Knowledge in Nutrition 1976:365 The Nutrition Foundation Washington, DC.
22. Mertz W. Chromium in human nutrition: a review. J. Nutr. 1993;123:626-633
23. Min J. K., Kim W. Y., Chae B. J., Chung I. B., Shin I. S., Choi Y. J., Han I. K. Effects of chromium picolinate on growth performance, carcass characteristics and serum traits in growing-finishing pigs. Asian-Australian J. Anim. Sci. 1997;10:8-14
24.
Mooradian A. D., Morley J. E. Micronutrient status in diabetes mellitus. Am. J. Clin. Nutr. 1987;45:877-895
25. Morgan L. M. Insulin secretion and the entero-insular axis. Flatt P. R. eds. Nutrient Regulation of Insulin Secretion 1992:2 Portland Press Ltd London, UK.
26. Mowat D. N. Organic Chromium in Animal Nutrition 1997 Chromium Books Guelph, ON, Canada.
27. National Research Council Nutrition Requirements of Swine 9th ed. 1988 National Academy Press Washington, DC.
28. National Research Council The Role of Chromium in Animal Nutrition 1997 National Academy Press Washington, DC.
29. Offenbacher K. G., Pi-Sunyer F. X. Beneficial effect of chromium-rich yeast on glucose tolerance and blood lipids in elderly subjects. Diabetes 1980;29:919-925[Abstract]
30. Page T. G., Southern L. L., Ward T. L., Thompson D. L., Jr Effect of chromium picolinate on growth and serum and carcass traits of growing-finishing pigs. J. Anim. Sci. 1993;71:656-662[Abstract]
31. Polonsky K., Frank B., Pugh W., Addis A., Karrison T., Meier P., Tager H., Rubenstein A. The limitations to and valid use of C-peptide as a marker of the secretion of insulin. Diabetes 1986;35:379-386[Abstract]
32. Polonsky K., Jaspan J. B., Pugh W., Cohen D., Schneider M., Schwartz T., Moossa A. R., Tager H., Rubenstein A. H. Metabolism of C-peptide in the dog: in vivo demonstration of the absence of hepatic extraction. J. Clin. Investig. 1983;72:1114-1123
33. Polonsky K. S., Rubenstein A. H. C-peptide as a measure of the secretion and hepatic extraction of insulin: pitfalls and limitations. Diabetes 1984;33:486-494[Abstract]
34. Rubenstein A. H., Clark J. L., Melani F., Steiner D. F. Secretion of proinsulin C-peptide by pancreatic ß cells and its circulation in blood. Nature (Lond.) 1969;224:697-699
35. Schwarz K., Mertz W. A glucose tolerance factor and its differentiation from Factor 3. Arch. Biochem. Biophys. 1957;72:515-518[Medline]
36. Striffler J. S., Law J. S., Polansky M. M., Bhathena S. J., Anderson R. A. Chromium improves insulin response to glucose in rats. Metab. Clin. Exp. 1995;44:1314-1320
37. Striffler J. S., Polansky M. M., Anserson R. A. Dietary chromium decreases insulin resistance in rats fed a high fat, mineral-imbalanced diet. Metab. Clin. Exp. 1998;47:396-400
38. Trottier, N. L. (1995) Protein Metabolism in the Lactating Sow. Doctoral thesis, University of Illinois at Urbana-Champaign, Urbana, IL.
39. Uusitupa M. J., Mykkanen L., Siitonen O., Laakso M., Sarlund H., Kolehmainen P., Rasanen T., Kumpulainen J., Pyorala K. Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels. Br. J. Nutr. 1992;68:209-216[Medline]
40. Van Cauter E., Mestrez F., Sturis J., Polonsky K. S. Estimation of insulin secretion rates from C-peptide levels. Diabetes 1992;41:368-377[Abstract]
41. Wahren J., Johansson B. L. New aspects of C-peptide physiology. Horm. Metab. Res. 1998;30:A2-A5[Medline]
42. Ward T. L., Berrio L. F., Southern L. L., Fernandez J. M., Thompson D. L. In-vivo and in-vitro evaluation of chromium tripicolinate on insulin binding in pig lever cell plasma membranes. FASEB J 1994;8:1124(abs)
43.
Ward T. L., Southern L. L., Bidner T. D. Interactive effects of dietary chromium tripicolinate and crude protein level in growing-finishing pigs provided inadequate and adequate pen space. J. Anim. Sci. 1997;75:1001-1008
44.
Watanabe R. M., Steil G. M., Bergman R. N. Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion. Am. J. Physiol. 1998;274:E172-E183
45. Wilson B. E., Gondy A. Effects of chromium supplementation on fasting insulin levels and lipid parameters in healthy, non-obese young subjects. Diabetes Res. Clin. Pract. 1995;28:179-184[Medline]
46. Wojcikowski C., Maier V., Dominiak G., Fussganger R., Pfeiffer E. F. Effects of synthetic rat C-peptide in normal and diabetic rats. Diabetologia 1983;25:288-290[Medline]
47. Yamamoto A., Wada O., Suzuki H. Purification and properties of biologically active chromium complex from bovine colostrum. J. Nutr. 1988;118:39-45
48. Zierath J. R., Handberg A., Tally M., Wallberg-Henriksson H. C-peptide stimulates glucose transport in isolated human skeletal muscle independent of insulin receptor and tyrosine kinase activation. Diabetologia 1996;39:306-313[Medline]
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