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(Journal of Nutrition. 2000;130:1274-1279.)
© 2000 The American Society for Nutritional Sciences


Article

High Chromium Yeast Supplementation Improves Glucose Tolerance in Pigs by Decreasing Hepatic Extraction of Insulin1 ,2

Xinfu Guan, Jacques J. Matte*, Pao K. Ku, Janet L. Snow3, Jeanne L. Burton and Nathalie L. Trottier4

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
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Twenty Landrace x Yorkshire cross pigs (body wt, 47.9 ± 2.9 kg) were used to evaluate effects of dietary high chromium (Cr) yeast supplementation on plasma kinetics of glucose, insulin and C-peptide. Pigs were provided free access to either a control diet (C) containing 204 µg Cr/kg or a diet supplemented with an additional 200 µg Cr/kg as high Cr yeast (CR) for between 23 and 30 d. After overnight food deprivation, dextrose (500 g/L) was infused through a jugular vein catheter at a dose of 0.5 g glucose/kg body weight with an infusion rate of 10 g glucose/min within 6 min. High Cr yeast supplementation did not affect body weight gain or food intake. There were no differences in fasting plasma concentrations of either glucose or C-peptide, although basal plasma concentration of insulin tended to be higher in pigs fed CR (P < 0.10). Plasma glucose concentrations were lower (P < 0.01) at postinfusion times 5, 10, 15 and 20 min in pigs fed CR. Plasma insulin concentrations in pigs fed CR were higher (P < 0.05) at 2 and 0 min before the completion of dextrose infusion. However, the increase in plasma insulin concentrations was not accompanied by a comparable elevation in plasma C-peptide concentrations. The 30-min (postinfusion) area of plasma glucose concentrations tended to be lower (P < 0.10) in pigs fed CR, but there were no differences in 30-min areas of either plasma insulin or plasma C-peptide concentrations between treatments. Plasma clearance rates of glucose, insulin and C-peptide were higher and their half-lives shorter (P < 0.05) in pigs fed CR. In conclusion, dietary high Cr yeast supplementation improved glucose tolerance, possibly through a decrease in hepatic extraction of insulin.


KEY WORDS: • chromium • glucose • insulin • C-peptide • pigs


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Chromium (Cr) is an essential nutrient for humans and animals (Mertz 1993Citation ). The main physiologic role of Cr is to increase insulin action or sensitivity in peripheral tissues (Anderson 1998Citation , Mowat 1997Citation ). Dietary Cr supplementation increases cellular uptake of glucose (Mooradian and Morley 1987Citation ) and decreases insulin resistance in rats fed a high fat, low Cr diet (containing 33 µg Cr/kg) (Striffler et al. 1998Citation ). Davis and Vincent (1997a)Citation recently proposed that Cr increases glucose tolerance through a Cr-dependent oligopeptide that activates insulin receptor tyrosine kinase activity. This in turns leads to the translocation of glucose transporter-4 from an intracellular vesicular compartment to the plasma membrane, stimulating glucose uptake into skeletal muscle and adipose tissue (Czech and Corvera 1999Citation ).

High Cr yeast contains a glucose tolerance factor (Mertz 1976Citation ). 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 1993Citation , Mowat 1997Citation , NRC 1997Citation ). High Cr yeast supplementation (9 g Brewers yeast/d) improved glucose tolerance in elderly subjects (Offenbacher and Pi-Sunyer 1980Citation ), 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. 1992Citation ). 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. 1995Citation ). 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. 1995Citation ). High Cr yeast did not affect either plasma insulin or plasma C-peptide response in elderly subjects (Uusitupa et al. 1992Citation ). 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. 1969Citation ); 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. 1983Citation ). 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 1988Citation , Polonsky et al. 1986Citation , Polonsky and Rubenstein 1984Citation , Van Cauter et al. 1992Citation , Watanabe et al. 1998Citation ).

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. 1994Citation ). 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
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Animals and experiment diets.

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 1Citation ) formulated to exceed nutrient requirements for swine (NRC 1988Citation ). 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 2Citation ).


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Table 1. Composition of the basal diet (as fed basis)

 

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Table 2. Average daily body weight gain (ADG) and average daily food intake (ADFI) in pigs fed control and Cr yeast–supplemented diets for 21 d12

 
Analysis of chromium in the basal diet.

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 1990Citation ). Chromium concentration in the digesta was determined using the Spectroflame ICP unit (Spectro, Littleton, MA) by the inductively coupled plasma method (Eaton et al. 1995Citation ). 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)Citation . 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 1997Citation ). 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
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Basal value, area and kinetics of plasma glucose.

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 3Citation ). High Cr yeast supplementation tended to decrease the 30-min area of plasma glucose concentration (P < 0.10) (Table 3)Citation 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 1Citation . 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 4Citation . 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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Table 3. Basal values, and responses of plasma glucose, insulin, and C-peptide in pigs fed control and Cr yeast-supplemented diets after an intravenous glucose tolerance test1

 


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Figure 1. Plasma glucose concentrations after an intravenous glucose tolerance test in pigs fed either a control or a high Cr yeast–supplemented diet. Dextrose (500 g/L) was infused through a jugular venous catheter at a bolus dose of 0.5 g glucose/kg body weight and a rate of 10 g glucose/min. Time indicates minutes relative to completion of dextrose infusion. Dashed line represents basal glucose concentration. Concentrations (least-square means ± SEM, n = 6) with ** differed (P < 0.01) between treatments.

 

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Table 4. Plasma kinetics of glucose, insulin and C-peptide after an intravenous glucose tolerance test in pigs fed control and Cr yeast–supplemented diets

 
Basal value, area and kinetics of plasma insulin.

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)Citation . High Cr yeast supplementation did not affect the 30-min area of plasma insulin concentration (Table 3)Citation 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 2Citation . 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 4Citation . 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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Figure 2. Plasma insulin concentrations after an intravenous glucose tolerance test in pigs fed either a control or a high Cr yeast–supplemented diet. Dextrose (500 g/L) was infused through a jugular venous catheter at a bolus dose of 0.5 g glucose/kg body weight and a rate of 10 g glucose/min. Time indicates minutes relative to completion of dextrose infusion. Dashed line represents basal insulin concentration. Concentrations (least-square means ± SEM, n = 6) with * and {dagger} indicating that values differed (P < 0.05) and tended to differ (P < 0.10) between treatments, respectively.

 
Basal value, area and kinetics of plasma C-peptide.

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)Citation . High Cr yeast supplementation did not affect the 30-min area of plasma C-peptide (Table 3)Citation 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 3Citation . 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 4Citation . 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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Figure 3. Plasma C-peptide concentrations after an intravenous glucose tolerance test in pigs fed either a control or a high Cr yeast–supplemented diet. Dextrose (500 g/L) was infused through a jugular venous catheter at a bolus dose of 0.5 g glucose/kg body weight and a rate of 10 g glucose/min. Time indicates minutes relative to completion of dextrose infusion. Dashed line represents basal C-peptide concentration. Concentrations (least-square means ± SEM, n = 6) at the same time did not differ (P > 0.05) or tended to differ (P > 0.1) between treatments.

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
High Cr yeast supplementation improved glucose tolerance, but did not affect basal plasma glucose concentration in pigs. These results are in agreement with recent studies in which neither Cr tripicolinate nor Cr nicotinate supplementation had an effect on basal plasma glucose level in pigs (Amoikon et al. 1995Citation , Evock-Clover et al. 1993Citation , Min et al. 1997Citation ) or in healthy human subjects (Wilson and Gondy 1995Citation ). No effect on basal plasma glucose concentration was observed in rats provided with 5 mg Cr/kg as CrCl3 added into the drinking water for 24 wk (Striffler et al. 1995Citation ). High Cr yeast supplementation tended to increase plasma glucose clearance rate by 31.3% and decreased plasma glucose clearance half-life by 25.5% in pigs, corresponding to a smaller 30-min area of plasma glucose concentrations after an i.v. GTT. This study confirmed that high Cr yeast supplementation increases glucose tolerance in pigs. Improvement in glucose tolerance was found in pigs fed Cr tripicolinate (Amoikon et al. 1995Citation ) and in rats provided CrCl3-containing drinking water (Striffler et al. 1995Citation ). These rats were fed a low Cr diet (33 µg/kg), resulting in impaired glucose tolerance. High Cr yeast also increased glucose tolerance in human subjects (Offenbacher and Pi-Sunyer 1980Citation ), but failed to improve glucose tolerance in elderly subjects with stable impaired glucose tolerance (Uusitupa et al. 1992Citation ). The glucose response to Cr supplementation is indirectly related to the degree of glucose intolerance (defined as a 90-min plasma glucose concentration > 5.56 mmol/L after an oral glucose tolerance test)(Anderson 1998Citation ).

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. 1997Citation , Lien et al. 1996Citation ), and in rats provided with CrCl3-containing drinking water for 12 wk (Striffler et al. 1995Citation ). No change in basal plasma insulin concentration was observed in pigs fed Cr tripicolinate (Min et al. 1997Citation , Page et al. 1993Citation ), in rats provided with CrCl3-containing drinking water for 24 wk (Striffler et al. 1995Citation ) or in healthy human subjects supplemented with Cr nicotinate (Wilson and Gondy 1995Citation ). On the contrary, basal plasma insulin concentration decreased in pigs supplemented with Cr tripicolinate (Amoikon et al. 1995Citation , Evock-Clover et al. 1993Citation ). 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. 1997Citation ). 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 1997Citation ). 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 1995Citation ). 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 1957Citation ) and/or the low-molecular-weight Cr-binding substances (Davis and Vincent 1997bCitation , Yamamoto et al. 1988Citation ).

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. 1983Citation ). 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. 1983Citation ). 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. 1983Citation , Polonsky and Rubenstein 1984Citation ). Peripheral plasma insulin concentration reflects a balance between insulin secretion per se and hepatic extraction of insulin (Morgan 1992Citation ). 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)Citation 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 1992Citation ). 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 1998Citation ). 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 1992Citation ). 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. 1994Citation ), 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. 1992Citation ). C-peptide stimulates glucose transporter in skeletal muscle independently of insulin receptor and tyrosine kinase activation (Zierath et al. 1996Citation ). C-peptide may inhibit glucose-induced insulin release (Leclercq-Meyer et al. 1997Citation , Wojcikowski et al. 1983Citation ). These findings indicate that C-peptide is itself a biologically active hormone (Wahren and Johansson 1998Citation ). 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-peptide’s 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 1996Citation ). 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 1999Citation ). 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 200–500 µg Cr/kg as Cr tripicolinate in a corn-soybean basal diet (NRC 1997Citation ). 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 1998Citation , NRC 1997Citation ).

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
 
The authors thank Ewen McMillan of Shur-Gain, A Member of Maple Leaf Food for laboratory analysis of chromium in the diet. The authors also thank Dale R. Romsos of the Department of Food Science and Human Nutrition and Allen H. Tucker of the Department of Animal Science at Michigan State University for their review of this manuscript.


    FOOTNOTES
 
1 Presented in part at the National Joint Meeting of ASAS and ADSA, July 29–August 1, 1997, Nashville, TN [Guan, X. F., Snow, J. L., Ku, P. K., Burton, J. L. & Trottier, N. L. (1997) Effect of dietary chromium supplementation on plasma glucose kinetics in barrows and gilts. J. Anim. Sci. 75 (suppl. 1): 189 (abs.)]. Back

2 Supported by Michigan State University Agricultural Experiment Station and JEFO Inc. (Quebec, Canada). Back

3 Current address: Department of Animal Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801. Back

5 Abbreviations used: ADFI, average daily food intake; ADG, average daily body weight gain; C, unsupplemented control diet; CR, high chromium yeast–supplemented diet; i.v.GTT, intravenous glucose tolerance test; k, plasma clearance rate; T1/2, half-life. Back

Manuscript received October 25, 1999. Initial review completed November 15, 1999. Revision accepted February 10, 2000.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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