Carassius auratus complex formula, including Carassius auratus, Rhizoma dioscoreae, Lycium chinense, and Rehmannia glutinosa Libosch, is a combination prescription of traditional Chinese medicine, which has always been used to treat diabetes mellitus in ancient China. In this study, we provided experimental evidence for the use of Carassius auratus complex formula in the treatment of high fat diet combined streptozotocin- (STZ-) induced type 2 diabetes. Carassius auratus complex formula aqueous extract was prepared and the effects of it on blood glucose, serum insulin, adipose tissue weight, oral glucose tolerance test (OGTT), total cholesterol, and triglyceride (TG) levels in mice were measured. Moreover, adiponectin, TG synthesis related gene expressions, and the inhibitory effect of aldose reductase (AR) were performed to evaluate its antidiabetic effects. After the 8-week treatment, blood glucose, insulin levels, and adipose tissue weight were significantly decreased. OGTT and HOMA-IR index showed improved glucose tolerance. It could also lower plasma TG, TC, and liver TG levels. Furthermore, Carassius auratus complex formula could inhibit the activity of AR and restore adiponectin expression in serum. Based on these findings, it is suggested that Carassius auratus complex formula possesses potent anti-diabetic effects on high fat diet combined STZ-induced diabetic mice. 1. Introduction Diabetes mellitus is a chronic metabolic disorder which affects people worldwide. By the year 2030, diabetes mellitus is estimated up to about 5% of the world’s population (i.e., 366 million people) [1]. More than 90% of diabetic patients account for type 2 diabetes [2]. The characteristic of type 2 diabetes is insulin resistance and glucose intolerance. Therefore, a newer strategy in the treatment of type 2 diabetes is to reduce insulin resistance in peripheral tissue and control of blood glucose level. Adiponectin and resistin are two kinds of adipose tissue releasing signals with different functions on the control of insulin sensitivity. Previous studies on adiponectin strongly suggest that lower adiponectin levels play an important role in the development of insulin resistance and metabolism disorder related diseases (such as type 2 diabetes and atherosclerosis) [3–5]. Moreover, more evidence suggests a role of resistin in the etiology of both insulin resistance and type 2 diabetes mellitus [6, 7]. Long-term elevated glucose level in the blood likely leads to a variety of diabetic complications such as neuropathy [8], nephropathy [9], and retinopathy [10]. These
References
[1]
H. N. Gouda, G. S. Sagoo, A.-H. Harding, J. Yates, M. S. Sandhu, and J. P. T. Higgins, “The association between the peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis,” American Journal of Epidemiology, vol. 171, no. 6, pp. 645–655, 2010.
[2]
A. S. Attele, Y.-P. Zhou, J.-T. Xie et al., “Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component,” Diabetes, vol. 51, no. 6, pp. 1851–1858, 2002.
[3]
C. Hug and H. F. Lodish, “The role of the adipocyte hormone adiponectin in cardiovascular disease,” Current Opinion in Pharmacology, vol. 5, no. 2, pp. 129–134, 2005.
[4]
P. E. Scherer, “Adipose tissue: from lipid storage compartment to endocrine organ,” Diabetes, vol. 55, no. 6, pp. 1537–1545, 2006.
[5]
T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara, K. Ueki, and K. Tobe, “Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1784–1792, 2006.
[6]
C. M. Steppan, S. T. Bailey, S. Bhat et al., “The hormone resistin links obesity to diabetes,” Nature, vol. 409, no. 6818, pp. 307–312, 2001.
[7]
S. S. Pang and Y. Y. Le, “Role of resistin in inflammation and inflammation-related diseases,” Cellular & Molecular Immunology, vol. 3, no. 1, pp. 29–34, 2006.
[8]
Z. A. Kamenov, R. A. Parapunova, and R. T. Georgieva, “Earlier development of diabetic neuropathy in men than in women with type 2 diabetes mellitus,” Gender Medicine, vol. 7, no. 6, pp. 600–615, 2010.
[9]
P. Rossing, “Diabetic nephropathy: worldwide epidemic and effects of current treatment on natural history,” Current Diabetes Reports, vol. 6, no. 6, pp. 479–483, 2006.
[10]
P. Romero-Aroca, J. Fernández-Balart, M. Baget-Bernaldiz et al., “Changes in the diabetic retinopathy epidemiology after 14 years in a population of Type 1 and 2 diabetic patients after the new diabetes mellitus diagnosis criteria and a more strict control of the patients,” Journal of Diabetes and Its Complications, vol. 23, no. 4, pp. 229–238, 2009.
[11]
C. E. Grimshaw, K. M. Bohren, C.-J. Lai, and K. H. Gabbay, “Human aldose reductase: pK of tyrosine 48 reveals the preferred ionization state for catalysis and inhibition,” Biochemistry, vol. 34, no. 44, pp. 14374–14384, 1995.
[12]
A. E. Raptis and G. Viberti, “Pathogenesis of diabetic nephropathy,” Experimental and Clinical Endocrinology and Diabetes, vol. 109, supplement 2, pp. S424–S437, 2001.
[13]
T. Oyama, Y. Miyasita, H. Watanabe, and K. Shirai, “The role of polyol pathway in high glucose-induced endothelial cell damages,” Diabetes Research and Clinical Practice, vol. 73, no. 3, pp. 227–234, 2006.
[14]
S. S. M. Chung and S. K. Chung, “Aldose reductase in diabetic microvascular complications,” Current Drug Targets, vol. 6, no. 4, pp. 475–486, 2005.
[15]
T. Yamauchi, J. Kamon, H. Waki et al., “The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance,” The Journal of Biological Chemistry, vol. 276, no. 44, pp. 41245–41254, 2001.
[16]
J. K. Grover, S. Yadav, and V. Vats, “Medicinal plants of India with anti-diabetic potential,” Journal of Ethnopharmacology, vol. 81, no. 1, pp. 81–100, 2002.
[17]
R. J. Marles and N. R. Farnsworth, “Antidiabetic plants and their active constituents,” Phytomedicine, vol. 2, no. 2, pp. 137–189, 1995.
[18]
X.-S. Shu, J.-H. Lv, J. Tao, G.-M. Li, H.-D. Li, and N. Ma, “Antihyperglycemic effects of total flavonoids from Polygonatum odoratum in STZ and alloxan-induced diabetic rats,” Journal of Ethnopharmacology, vol. 124, no. 3, pp. 539–543, 2009.
[19]
W. W. Liu, T. Ogata, S. Sato, K. Unoura, and J.-I. Onodera, “Superoxide scavenging activities of sixty Chinese medicines determined by an ESR spin-trapping method using electrogenerated superoxide,” Yakugaku Zasshi, vol. 121, no. 4, pp. 265–270, 2001.
[20]
H. A. Jung, Y. J. Jung, N. Y. Yoon et al., “Inhibitory effects of Nelumbo nucifera leaves on rat lens aldose reductase, advanced glycation endproducts formation, and oxidative stress,” Food and Chemical Toxicology, vol. 46, no. 12, pp. 3818–3826, 2008.
[21]
X. Gao, B. Li, H. Jiang, F. Liu, D. Xu, and Z. Liu, “Dioscorea opposita reverses dexamethasone induced insulin resistance,” Fitoterapia, vol. 78, no. 1, pp. 12–15, 2007.
[22]
C. L. Lin, C. C. Wang, S. C. Chang, B. S. Inbaraj, and B. H. Chen, “Antioxidative activity of polysaccharide fractions isolated from Lycium barbarum Linnaeus,” International Journal of Biological Macromolecules, vol. 45, no. 2, pp. 146–151, 2009.
[23]
W.-J. Huang, H.-S. Niu, M.-H. Lin, J.-T. Cheng, and F.-L. Hsu, “Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats,” Journal of Natural Products, vol. 73, no. 6, pp. 1170–1172, 2010.
[24]
K. Srinivasan, B. Viswanad, L. Asrat, C. L. Kaul, and P. Ramarao, “Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening,” Pharmacological Research, vol. 52, no. 4, pp. 313–320, 2005.
[25]
Y. Wang, T. Campbell, B. Perry, C. Beaurepaire, and L. Qin, “Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats,” Metabolism, vol. 60, no. 2, pp. 298–305, 2011.
[26]
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, “Protein measurement with the Folin phenol reagent,” The Journal of Biological Chemistry, vol. 193, no. 1, pp. 265–275, 1951.
[27]
J. Folch, M. Lees, and S. G. H. Sloane, “A simple method for the isolation and purification of total lipides from animal tissues,” The Journal of Biological Chemistry, vol. 226, no. 1, pp. 497–509, 1957.
[28]
Y. S. Kim, N. H. Kim, D. H. Jung et al., “Genistein inhibits aldose reductase activity and high glucose-induced TGF-β2 expression in human lens epithelial cells,” European Journal of Pharmacology, vol. 594, no. 1–3, pp. 18–25, 2008.
[29]
T. Nishinaka and C. Yabe-Nishimura, “EGF receptor-ERK pathway is the major signaling pathway that mediates upregulation of aldose reductase expression under oxidative stress,” Free Radical Biology and Medicine, vol. 31, no. 2, pp. 205–216, 2001.
[30]
J. R. Baker, P. A. Metcalf, and R. N. Johnson, “Use of protein-based standards in automated colorimetric determinations of fructosamine in serum,” Clinical Chemistry, vol. 31, no. 9, pp. 1550–1554, 1985.
[31]
J. R. Petrie, E. R. Pearson, and C. Sutherland, “Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology,” Biochemical Pharmacology, vol. 81, no. 4, pp. 471–477, 2011.
[32]
B. B. Lowell and G. I. Shulman, “Mitochondrial dysfunction and type 2 diabetes,” Science, vol. 307, no. 5708, pp. 384–387, 2005.
[33]
Y. Shi and D. Cheng, “Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism,” The American Journal of Physiology—Endocrinology and Metabolism, vol. 297, no. 1, pp. E10–E18, 2009.
[34]
A. Nkondjock and O. Receveur, “Fish-seafood consumption, obesity, and risk of type 2 diabetes: an ecological study,” Diabetes and Metabolism, vol. 29, no. 6, pp. 635–642, 2003.
[35]
D. Fedor and D. S. Kelley, “Prevention of insulin resistance by n-3 polyunsaturated fatty acids,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 12, no. 2, pp. 138–146, 2009.
[36]
A. Nanri, T. Mizoue, M. Noda et al., “Fish intake and type 2 diabetes in Japanese men and women: the Japan Public Health Center-based prospective study,” The American Journal of Clinical Nutrition, vol. 94, no. 3, pp. 884–891, 2011.
[37]
P. G. McTernan, C. L. McTernan, R. Chetty et al., “Increased resistin gene and protein expression in human abdominal adipose tissue,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 5, pp. 2407–2410, 2002.
[38]
M. Slawik and A. J. Vidal-Puig, “Lipotoxicity, overnutrition and energy metabolism in aging,” Ageing Research Reviews, vol. 5, no. 2, pp. 144–164, 2006.
[39]
E. E. Kershaw and J. S. Flier, “Adipose tissue as an endocrine organ,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2548–2556, 2004.
[40]
J.-P. Bastard, M. Maachi, C. Lagathu et al., “Recent advances in the relationship between obesity, inflammation, and insulin resistance,” European Cytokine Network, vol. 17, no. 1, pp. 4–12, 2006.
[41]
T. Yamauchi, J. Kamon, H. Waki et al., “The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity,” Nature Medicine, vol. 7, no. 8, pp. 941–946, 2001.
[42]
U.S. Department of Health and Human Services, Diabetes: A National Plan for Action, pp. 19–22, U.S. Department of Health and Human Services, 2004.
[43]
R. G. Gonzalez, P. Barnett, and J. Aguayo, “Direct measurement of polyol pathway activity in the ocular lens,” Diabetes, vol. 33, no. 2, pp. 196–199, 1984.
[44]
K. V. Ramana, D. Chandra, S. Srivastava, A. Bhatnagar, and S. K. Srivastava, “Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells,” The FASEB Journal, vol. 17, no. 3, pp. 417–425, 2003.
[45]
J. P. Shield, K. Poyser, L. Hunt, and C. A. Pennock, “Fructosamine and glycated haemoglobin in the assessment of long term glycaemic control in diabetes,” Archives of Disease in Childhood, vol. 71, no. 5, pp. 443–445, 1994.
[46]
“Diabetes UK. HbA1c (Glycated haemoglobin) and fructosamine,” 2011, http://www.diabetes.org.uk/hba1c.
[47]
A. P. Robertson, “Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes,” The Journal of Biological Chemistry, vol. 279, no. 41, pp. 42351–42354, 2004.