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Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion

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Abstract

Purpose

We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice.

Methods

In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured.

Results

The db–H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db–L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db–L mixture mice showed significantly higher blood glucose after 30 min than db–H mixture mice. However, db mice administered starch–H mixture showed significantly higher blood glucose 120–300 min post-administration than db–L mixture mice, although both groups exhibited similar insulin levels.

Conclusions

High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

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References

  1. Zimmet P, Alberti KGMM, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787

    Article  CAS  Google Scholar 

  2. Remuzzi G, Benigni A, Remuzzi A (2006) Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 116:288–296

    Article  CAS  Google Scholar 

  3. Magkos F, Yannakoulia M, Chan JL, Mantzoros CS (2009) Management of the metabolic syndrome and type 2 diabetes through lifestyle modification. Ann Rev Nutr 29:223–256

    Article  CAS  Google Scholar 

  4. Layman DK, Clifton P, Gannon MC, Krauss RM, Nuttall FQ (2008) Protein in optimal health: heart disease and type 2 diabetes. Am J Clin Nutr 87:1571S–1575S

    CAS  Google Scholar 

  5. Pan Y, Guo LL, Jin HM (2008) Low-protein diet for diabetic nephropathy: a meta-analysis of randomized controlled trials. Am J Clin Nutr 88:660–666

    CAS  Google Scholar 

  6. Rietman A, Schwarz J, Tomé D, Kok FJ, Mensink M (2014) High dietary protein intake, reducing or eliciting insulin resistance? Eur J Clin Nutr 68:973–979

    Article  CAS  Google Scholar 

  7. Tsunehara CH, Leonetti DL, Fujimoto WF (1990) Diet of second-generation Japanese–American men with and without non-insulin-dependent diabetes. Am J Clin Nutr 52:731–738

    CAS  Google Scholar 

  8. Metges CC, Barth CA (2000) Metabolic consequences of a high dietary-protein intake in adulthood: assessment of the available evidence. J Nutr 130:886–889

    CAS  Google Scholar 

  9. Kuroe A, Fukushima M, Usami M et al (2003) Impaired β-cell function and insulin sensitivity in Japanese subjects with normal glucose tolerance. Diabetes Res Clin Pract 59:71–77

    Article  CAS  Google Scholar 

  10. Shafrir E, Ziv E, Mosthaf L (1999) Nutritionally induced insulin resistance and receptor defect leading to β-cell failure in animal models. Ann N Y Acad Sci 892:223–246

    Article  CAS  Google Scholar 

  11. Davis RC, Castellani LW, Hosseini M et al (2010) Early hepatic insulin resistance precedes the onset of diabetes in obese C57BLKS-db/db mice. Diabetes 59:1616–1625

    Article  CAS  Google Scholar 

  12. Arimura E, Horiuchi M, Kawaguchi H, Miyoshi N, Aoyama K, Takeuchi T (2013) Low-protein diet improves blood and urinary glucose levels and renal manifestations of diabetes in C57BLKS-db/db mice. Eur J Nutr 52:813–824

    Article  CAS  Google Scholar 

  13. Goldberg T, Weijing C, Peppa M et al (2004) Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 104:1287–1291

    Article  CAS  Google Scholar 

  14. Gannon MC, Nuttall FQ, Saeed A, Jordan K, Hoover H (2003) An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes. Am J Clin Nutr 78:734–741

    CAS  Google Scholar 

  15. Chen H, Charlat O, Tartaglia LA et al (1996) Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491495

    Google Scholar 

  16. Stechman MJ, Ahmad BN, Loh NY et al (2010) Establishing normal plasma and 24-hour urinary biochemistry ranges in C3H, BALB/c and C57BL/6 J mice following acclimatization in metabolic cage. Lab Anim 44:218–225

    Article  CAS  Google Scholar 

  17. Burke BJ, Hartog M, Heaton KW, Hooper S (1982) Assessment of the metabolic effects of dietary carbohydrate and fibre by measuring urinary excretion of C-peptide. Hum Nutr Clin Nutr 36:373–380

    CAS  Google Scholar 

  18. Linn T, Strate C, Schneider K (1999) Diet promotes β-cell loss by apoptosis in prediabetic nonobese diabetic mice. Endocrinology 140:3767–3773

    CAS  Google Scholar 

  19. Correa-Rotter R, Hostetter TH, Rosenberg ME (1992) Effect of dietary protein on renin and angiotensinogen gene expression after renal ablation. Am J Physiol 262:F631–F638

    CAS  Google Scholar 

  20. Teixeira SR, Tappenden KA, Erdman JW Jr (2003) Altering dietary protein type and quantity reduces urinary albumin excretion without affecting plasma glucose concentrations in BKS.cg-m +Leprdb/+ Leprdb (db/db) mice. J Nutr 133:673–678

    CAS  Google Scholar 

  21. Nordquist L, Lai EY, Sjöquist M, Patzak A, Persson AEG (2008) Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism. Am J Physiol Regul Integr Comp Physiol 294:R836–R841

    Article  CAS  Google Scholar 

  22. Savino A, Pelliccia P, Giannini C et al (2011) Implications for kidney disease in obese children and adolescents. Pediatr Nephrol 26:749–758

    Article  Google Scholar 

  23. Aguilera A, Reis de Souza TC, Mariscal-Landín G, Escobar K, Montaño S, Bernal MG (2015) Standardized ileal digestibility of proteins and amino acids in sesame expeller and soya bean meal in weaning piglets. J Anim Physiol Anim Nutr 99:728–736

    Article  CAS  Google Scholar 

  24. Jensen KT, Löbmann K, Rades T, Grohganz H (2014) Involving co-amorphous drug formulations by the addition of the highly water soluble amino acid, proline. Pharmaceutics 6:416–435

    Article  CAS  Google Scholar 

  25. Krebs HA, Notton BM, Hems R (1966) Gluconeogenesis in mouse-liver slices. Biochem J 101:607–617

    Article  CAS  Google Scholar 

  26. Chen Y, Cao Y, Zhao L, Kong X, Hua Y (2014) Macronutrients and micronutrients of soybean oil bodies extracted at different pH. J Food Sci 79:C1285–C1291

    Article  CAS  Google Scholar 

  27. Bois-Joyeux B, Chanez M, Azzout B, Peret J (1986) Studies on the early changes in rat hepatic fructose 2,6-bisphosphate and enzymes in response to a high protein diet. J Nutr 116:446–454

    CAS  Google Scholar 

  28. Li H, Lee J, He C, Zou M-H, Xie Z (2014) Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids. Am J Physiol Endocrinol Metab 306:E197–E209

    Article  CAS  Google Scholar 

  29. Peters AL, Davidson MB (1993) Protein and fat effects on glucose responses and insulin requirements in subjects with insulin-dependent diabetes mellitus. Am J Clin Nutr 58:555–560

    CAS  Google Scholar 

  30. Kiehm TG, Anderson JW, Ward K (1976) Beneficial effects of a high carbohydrate, high fiber diet on hyperglycemic diabetic men. Am J Clin Nutr 29:895–899

    CAS  Google Scholar 

  31. Chandalia M, Garg A, Lutjohann D et al (2000) Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. N Engl J Med 342:1392–1398

    Article  CAS  Google Scholar 

  32. The Council for Science and Technology, Ministry of Education, Culture, Sports, Science and Technology, JAPAN (2010) Amino acid composition of foods in 2010, Standard tables of food composition in Japan. Official Gazette Co-operation of Japan, Tokyo

    Google Scholar 

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Acknowledgments

We thank Chiko Nishinosono for administrative assistance and the Joint Research Laboratory, Kagoshima University Graduate School of Medical and Dental Sciences, for the use of its facilities. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (#22500650 and #25350873 to E. A. and #21590704 to M. H.) and funded by the Kodama Memorial Fund for Medical Science Research.

Author contributions

E.A., W.P., and M.H. obtained and analysed data and wrote the manuscript. A.M., M.N., M.A., and M.U. contributed to discussions of experimental design and analysis and reviewed the manuscript.

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Author notes

  1. Ancah Caesarina Novi Marchianti

    Present address: Medical Faculty of Jember University, Kalimantan Street 37, East Java, Indonesia

Authors and Affiliations

  1. Major in Food and Nutrition, Department of Life and Environmental Science, Kagoshima Prefectural College, 1-52-1 Shimo-Ishiki, Kagoshima, 890-0005, Japan

    Emi Arimura

  2. Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Emi Arimura, Wijang Pralampita Pulong, Ancah Caesarina Novi Marchianti, Miwa Nakakuma, Masaharu Abe, Miharu Ushikai & Masahisa Horiuchi

  3. Takata Hospital, 5-1 Horie-cho, Kagoshima, 892-0824, Japan

    Miwa Nakakuma

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Correspondence to Masahisa Horiuchi.

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This study was approved by the Ethics Committee for Animal Experimentation at Kagoshima University.

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Arimura, E., Pulong, W.P., Marchianti, A.C.N. et al. Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion. Eur J Nutr 56, 237–246 (2017). https://doi.org/10.1007/s00394-015-1075-y

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