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Published in: Nutrition & Metabolism 1/2015

Open Access 01-12-2015 | Research

Low-calcium diet prevents fructose-induced hyperinsulinemia and ameliorates the response to glucose load in rats

Authors: Anna Voznesenskaya, Michael G. Tordoff

Published in: Nutrition & Metabolism | Issue 1/2015

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Abstract

Background

Consuming a fructose-rich diet leads to hyperinsulinemia, impaired glucose tolerance, and insulin resistance. In humans, the consumption of high levels of refined sugars often coincides with a diet containing suboptimal levels of calcium. Calcium and carbohydrate metabolism interact, so there is potential for fructose to have different health outcomes depending on whether the diet is calcium-rich or calcium-poor.

Methods

We evaluated the metabolic effects of feeding fructose to rats that were maintained on either a calcium-replete diet or a low-calcium diet. Growing male Sprague Dawley rats were fed diets based on the AIN-93G formulation, with the main source of carbohydrate derived either from a mixture of cornstarch and sucrose or from fructose. Half the rats given each carbohydrate source were fed calcium at recommended levels (125 mmol/kg Ca2+); the others were fed a diet low in calcium (25 mmol/kg Ca2+). At various times, glucose and insulin tolerance tests were conducted to assess glucose metabolism.

Results

Rats fed low-calcium diet had lower fasting insulin levels irrespective of the carbohydrate source they ate. They had a normal glycemic response to a glucose load and did not develop hyperinsulinemia under conditions of fructose feeding. The drop in blood glucose levels in response to insulin injection was larger in rats fed low-calcium diet than in those fed calcium-replete diet.

Conclusions

Low-calcium diet prevented fructose-induced hyperinsulinemia and improved glucose handling under conditions of fructose feeding. Potential mechanisms underlying these effects of the low-calcium diet remain to be determined, but possibilities include impairment of insulin release from the pancreas and improved peripheral insulin sensitivity.
Literature
1.
go back to reference Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345(11):790–7.CrossRef Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345(11):790–7.CrossRef
2.
go back to reference Gross LS, Li L, Ford ES, Liu S. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr. 2004;79(5):774–9. Gross LS, Li L, Ford ES, Liu S. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr. 2004;79(5):774–9.
3.
go back to reference Lanaspa MA, Ishimoto T, Li N, Cicerchi C, Orlicky DJ, Ruzycki P, et al. Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nat Commun. 2013;4:2434. Lanaspa MA, Ishimoto T, Li N, Cicerchi C, Orlicky DJ, Ruzycki P, et al. Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nat Commun. 2013;4:2434.
4.
go back to reference Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr. 2002;76(5):911–22. Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr. 2002;76(5):911–22.
5.
go back to reference Popkin BM, Nielsen SJ. The sweetening of the world’s diet. Obes Res. 2003;11(11):1325–32.CrossRef Popkin BM, Nielsen SJ. The sweetening of the world’s diet. Obes Res. 2003;11(11):1325–32.CrossRef
6.
go back to reference Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005;63(5):133–57.CrossRef Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005;63(5):133–57.CrossRef
7.
go back to reference Welsh JA, Sharma AJ, Grellinger L, Vos MB. Consumption of added sugars is decreasing in the United States. Am J Clin Nutr. 2011;94(3):726–34.CrossRef Welsh JA, Sharma AJ, Grellinger L, Vos MB. Consumption of added sugars is decreasing in the United States. Am J Clin Nutr. 2011;94(3):726–34.CrossRef
8.
go back to reference Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010;110(9):1307–21.CrossRef Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010;110(9):1307–21.CrossRef
9.
go back to reference Tobey TA, Mondon CE, Zavaroni I, Reaven GM. Mechanism of insulin resistance in fructose-fed rats. Metabolism. 1982;31(6):608–12.CrossRef Tobey TA, Mondon CE, Zavaroni I, Reaven GM. Mechanism of insulin resistance in fructose-fed rats. Metabolism. 1982;31(6):608–12.CrossRef
10.
go back to reference Zavaroni I, Sander S, Scott S, Reaven GM. Effect of fructose feeding on insulin secretion and insulin action in the rat. Metabolism. 1980;29(10):970–3.CrossRef Zavaroni I, Sander S, Scott S, Reaven GM. Effect of fructose feeding on insulin secretion and insulin action in the rat. Metabolism. 1980;29(10):970–3.CrossRef
11.
go back to reference Malik VS, Popkin BM, Bray GA, Després J-P, Hu FB. Sugar Sweetened Beverages, Obesity, Type 2 Diabetes and Cardiovascular Disease risk. Circulation. 2010;121(11):1356–64.CrossRef Malik VS, Popkin BM, Bray GA, Després J-P, Hu FB. Sugar Sweetened Beverages, Obesity, Type 2 Diabetes and Cardiovascular Disease risk. Circulation. 2010;121(11):1356–64.CrossRef
12.
go back to reference Vartanian LR, Schwartz MB, Brownell KD. Effects of soft drink consumption on nutrition and health: a systematic review and meta-analysis. Am J Public Health. 2007;97(4):667–75.CrossRef Vartanian LR, Schwartz MB, Brownell KD. Effects of soft drink consumption on nutrition and health: a systematic review and meta-analysis. Am J Public Health. 2007;97(4):667–75.CrossRef
13.
go back to reference Harnack L, Stang J, Story M. Soft drink consumption among US children and adolescents: nutritional consequences. J Am Diet Assoc. 1999;99(4):436–41.CrossRef Harnack L, Stang J, Story M. Soft drink consumption among US children and adolescents: nutritional consequences. J Am Diet Assoc. 1999;99(4):436–41.CrossRef
14.
go back to reference Beaulieu C, Kestekian R, Havrankova J, Gascon-Barre M. Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo. Diabetes. 1993;42(1):35–43.CrossRef Beaulieu C, Kestekian R, Havrankova J, Gascon-Barre M. Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo. Diabetes. 1993;42(1):35–43.CrossRef
15.
go back to reference Milner RD, Hales CN. The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia. 1967;3(1):47–9.CrossRef Milner RD, Hales CN. The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia. 1967;3(1):47–9.CrossRef
16.
go back to reference Rayssiguier Y, Chevalier F, Gueux E, Remesy C, Demigne C. Glucose-stimulated insulin secretion in rats with normal plasma calcium levels: effects of calcium deficiency. J Nutr. 1982;112(9):1801–4. Rayssiguier Y, Chevalier F, Gueux E, Remesy C, Demigne C. Glucose-stimulated insulin secretion in rats with normal plasma calcium levels: effects of calcium deficiency. J Nutr. 1982;112(9):1801–4.
17.
go back to reference Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820–5. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820–5.
18.
go back to reference Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017–29.CrossRef Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017–29.CrossRef
19.
go back to reference Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823–5.CrossRef Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823–5.CrossRef
20.
go back to reference Chandler PT, Cragle RG. Investigation of Calcium, Phosphorus and Vitamin D3 Relationships in Rats by Multiple Regression Techniques. J Nutr. 1962;78(1):28–36. Chandler PT, Cragle RG. Investigation of Calcium, Phosphorus and Vitamin D3 Relationships in Rats by Multiple Regression Techniques. J Nutr. 1962;78(1):28–36.
21.
go back to reference Bernhart FW, Savini S, Tomarelli RM. Calcium and Phosphorus Requirements for Maximal Growth and Mineralization of the Rat. J Nutr. 1969;98(4):443–8. Bernhart FW, Savini S, Tomarelli RM. Calcium and Phosphorus Requirements for Maximal Growth and Mineralization of the Rat. J Nutr. 1969;98(4):443–8.
22.
go back to reference Tordoff MG. NaCl ingestion ameliorates plasma indexes of calcium deficiency. Am J Physiol Regul Integr Comp Physiol. 1997;273(1 Pt 2):R423–32. Tordoff MG. NaCl ingestion ameliorates plasma indexes of calcium deficiency. Am J Physiol Regul Integr Comp Physiol. 1997;273(1 Pt 2):R423–32.
23.
go back to reference Tordoff MG, Okiyama A. Daily rhythm of NaCl intake in rats fed low-Ca2+ diet: relation to plasma and urinary minerals and hormones. Am J Physiol Regul Integr Comp Physiol. 1996;270(3 Pt 2):R505–17. Tordoff MG, Okiyama A. Daily rhythm of NaCl intake in rats fed low-Ca2+ diet: relation to plasma and urinary minerals and hormones. Am J Physiol Regul Integr Comp Physiol. 1996;270(3 Pt 2):R505–17.
24.
go back to reference Ayala JE, Samuel VT, Morton GJ, Obici S, Croniger CM, Shulman GI, et al. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech. 2010;3(9–10):525–34.CrossRef Ayala JE, Samuel VT, Morton GJ, Obici S, Croniger CM, Shulman GI, et al. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech. 2010;3(9–10):525–34.CrossRef
25.
go back to reference Tai MM. A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care. 1994;17(2):152–4.CrossRef Tai MM. A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care. 1994;17(2):152–4.CrossRef
26.
go back to reference Allison DB, Paultre F, Maggio C, Mezzitis N, Pi-Sunyer FX. The use of areas under curves in diabetes research. Diabetes Care. 1995;18(2):245–50.CrossRef Allison DB, Paultre F, Maggio C, Mezzitis N, Pi-Sunyer FX. The use of areas under curves in diabetes research. Diabetes Care. 1995;18(2):245–50.CrossRef
27.
go back to reference Calle C, Maestro B, Garcia-Arencibia M. Genomic actions of 1,25-dihydroxyvitamin D3 on insulin receptor gene expression, insulin receptor number and insulin activity in the kidney, liver and adipose tissue of streptozotocin-induced diabetic rats. BMC Mol Biol. 2008;9:65.CrossRef Calle C, Maestro B, Garcia-Arencibia M. Genomic actions of 1,25-dihydroxyvitamin D3 on insulin receptor gene expression, insulin receptor number and insulin activity in the kidney, liver and adipose tissue of streptozotocin-induced diabetic rats. BMC Mol Biol. 2008;9:65.CrossRef
28.
go back to reference Maestro B, Campion J, Davila N, Calle C. Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J. 2000;47(4):383–91.CrossRef Maestro B, Campion J, Davila N, Calle C. Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J. 2000;47(4):383–91.CrossRef
29.
go back to reference Maestro B, Molero S, Bajo S, Davila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D (3). Cell Biochem Funct. 2002;20(3):227–32.CrossRef Maestro B, Molero S, Bajo S, Davila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D (3). Cell Biochem Funct. 2002;20(3):227–32.CrossRef
30.
go back to reference Tordoff MG, Hughes RL, Pilchak DM. Calcium intake by rats: influence of parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D. Am J Physiol Regul Integr Comp Physiol. 1998;274(1):R214–31. Tordoff MG, Hughes RL, Pilchak DM. Calcium intake by rats: influence of parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D. Am J Physiol Regul Integr Comp Physiol. 1998;274(1):R214–31.
31.
go back to reference Zhang Q, Tordoff MG. No effect of dietary calcium on body weight of lean and obese mice and rats. Am J Physiol Regul Integr Comp Physiol. 2004;286(4):R669–77.CrossRef Zhang Q, Tordoff MG. No effect of dietary calcium on body weight of lean and obese mice and rats. Am J Physiol Regul Integr Comp Physiol. 2004;286(4):R669–77.CrossRef
32.
go back to reference Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens. 2003;16(11 Pt 1):973–8.CrossRef Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA. Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens. 2003;16(11 Pt 1):973–8.CrossRef
33.
go back to reference Verhaeghe J, Van Herck E, Van Bree R, Van Assche FA, Bouillon R. Osteocalcin during the reproductive cycle in normal and diabetic rats. J Endocrinol. 1989;120(1):143–51.CrossRef Verhaeghe J, Van Herck E, Van Bree R, Van Assche FA, Bouillon R. Osteocalcin during the reproductive cycle in normal and diabetic rats. J Endocrinol. 1989;120(1):143–51.CrossRef
34.
go back to reference Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142(2):296–308.CrossRef Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142(2):296–308.CrossRef
35.
go back to reference Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.CrossRef Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.CrossRef
36.
go back to reference Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone. 2012;50(2):568–75.CrossRef Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone. 2012;50(2):568–75.CrossRef
37.
go back to reference Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications. J Am Coll Nutr. 2002;21(2):146s–51s.CrossRef Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications. J Am Coll Nutr. 2002;21(2):146s–51s.CrossRef
38.
go back to reference Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium. Faseb J. 2000;14(9):1132–8. Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium. Faseb J. 2000;14(9):1132–8.
39.
go back to reference Paradis S, Cabanac M. Calcium deficiency cannot induce obesity in rats. Physiol Behav. 2005;85(3):259–64.CrossRef Paradis S, Cabanac M. Calcium deficiency cannot induce obesity in rats. Physiol Behav. 2005;85(3):259–64.CrossRef
40.
go back to reference Bertone-Johnson ER, Hankinson SE, Bendich A, Johnson SR, Willett WC, Manson JE. Calcium and vitamin D intake and risk of incident premenstrual syndrome. Arch Intern Med. 2005;165(11):1246–52.CrossRef Bertone-Johnson ER, Hankinson SE, Bendich A, Johnson SR, Willett WC, Manson JE. Calcium and vitamin D intake and risk of incident premenstrual syndrome. Arch Intern Med. 2005;165(11):1246–52.CrossRef
41.
go back to reference Garland CF, Garland FC, Gorham ED. Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Ann N Y Acad Sci. 1999;889:107–19.CrossRef Garland CF, Garland FC, Gorham ED. Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Ann N Y Acad Sci. 1999;889:107–19.CrossRef
42.
go back to reference Weaver CM. Calcium requirements of physically active people. Am J Clin Nutr. 2000;72(2):579s–84s. Weaver CM. Calcium requirements of physically active people. Am J Clin Nutr. 2000;72(2):579s–84s.
43.
go back to reference Heaney RP. Lifelong calcium intake and prevention of bone fragility in the aged. Calcif Tissue Int. 1991;49:S42–5.CrossRef Heaney RP. Lifelong calcium intake and prevention of bone fragility in the aged. Calcif Tissue Int. 1991;49:S42–5.CrossRef
Metadata
Title
Low-calcium diet prevents fructose-induced hyperinsulinemia and ameliorates the response to glucose load in rats
Authors
Anna Voznesenskaya
Michael G. Tordoff
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Nutrition & Metabolism / Issue 1/2015
Electronic ISSN: 1743-7075
DOI
https://doi.org/10.1186/s12986-015-0035-0

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