Yüksek Yağlı Diyet ile Beslenen Sıçanlarda Krom Histidinatın Farklı İzomerlerinin Pankreas GLUT-2, IRS-1 ve GLP-1R Üzerine Etkileri
Krom (Cr), insülin aktivitesi için esansiyel bir iz elementtir, insülin reseptörüne bağlanır,karbonhidrat ve lipit metabolizmasının düzenlenmesi de dahil olmak üzere birçok fonksiyonu vebelki de tüm fonksiyonlarında insülinin etkisini güçlendirir. Bu çalışmanın amacı, yüksek yağlı diyet(YYD) ile beslenen sıçanlarda, krom histidinatın (CrHis) üç farklı izomerinin, pankreas glikoztaşıyıcı protein 2 (GLUT-2), insülin reseptör substrat (IRS-1) ve glukagon benzeri peptid 1 reseptör(GLP-1R) protein düzeyleri üzerindeki etkilerini araştırmaktır. Çalışmada, 42 adet Sprague-Dawleyırkı sıçan rastgele altı gruba (n=7) ayrıldı. Sıçanlar 1:standart diyet ile beslenen (Kontrol); 2: YYDile beslenen; 3: YYD ile CrHis saflaştırılmış izomer 1 (CrHis1); 4: YYD ile CrHis ile saflaştırılmışizomer 2 (CrHis2); 5: CrHis ile saflaştırılmış izomer 3 (CrHis3); 6: YYD ile üç izomer CrHis(CrHisM) karışımı ile beslenen şeklinde gruplandırıldı. CrHis izomerleri farklı kaynaklardansağlanmasına karşın sıçanlara aynı miktarda Cr (10 µg elementel Cr/kg CA/gün) verildi. Sıçanlar,insülin direncini indüklemek için yüksek yağlı bir diyetle beslendi. CrHis izomerlerinin uygulanması,YYD ile artan pankreas insülin düzeylerini iyileştirdi. CrHis izomer gruplarındaki insülin seviyeleriYYD grubuna göre anlamlı derecede düşük bulundu (P
The Effects of Different Isomers of the Chromium Histidinate on Pancreas GLUT2, GLP-1R and IRS-1 in Rats Fed High-Fat Diet
Chromium (Cr) is an essential trace element for optimal insulin activity. It binds to the insulin receptor and potentiates many, and perhaps all, of its functions including the regulation of carbohydrate and lipid metabolism. The objective of this study was to investigate the effects of novel purified isomers of chromium histidinate (CrHis on protein levels of pancreatic glucose transporter protein 2 (GLUT-2), insulin receptor substrate (IRS-1) and glucagon-like peptide 1 receptor (GLP-1R). Forty-two Sprague–Dawley rats allocated to six groups (n=7). The rats were fed either 1: a standard diet (Control) or 2: a high-fat diet (HFD) or 3: a HFD with CrHis purified isomer 1 (CrHis1) or 4: a HFD with CrHis purified isomer 2 (CrHis2) or 5: a HFD with CrHis purified isomer 3 (CrHis3) or 6: a HFD with a mixture of three isomers of CrHis (CrHisM). Rats were fed the same amount of Cr (10 µg elemental Cr/kg BW/day), but from different sources of CrHis isomers. Rats fed a high-fat diet to induce insulin resistance. The administration of CrHis isomers showed an improvement in the HFD-enhanced pancreatic insulin levels. The insulin levels in the CrHis isomer groups were measured significantly lower than the HFD group (P
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- International Diabetes Federation. “IDF Diabetes Atlas 8th
Edition International Diabetes Federation, Brussels,
Belgium”. https://www.idf.org/e-library/epidemiologyresearch/diabetes-atlas/134-idf-diabetes-atlas-8th-edition.
html/ 10.05.2017.
- Nandipati KC, Subramanian S, Agrawal DK. Protein
kinases: Mechanisms and downstream targets in
inflammation-mediated obesity and insulin resistance. Mol
Cell Biochem 2017; 426: 27-45.
- Liu S, Duan R, Wu Y, et al. Effects of vaspin on insulin
resistance in rats and underlying mechanisms. Sci Rep
2018; 8: 13542.
- Gu JJ, Gao FY, Zhao TY. A preliminary investigation of the
mechanisms underlying the effect of berberine in preventing high-fat diet-induced insulin resistance in rats. J
Physiol Pharmacol 2012; 63: 505-513.
- Gheibi S, Kashfi K, Ghasemi A. A practical guide for
induction of type-2 diabetes in rat: Incorporating a high-fat
diet and streptozotocin. Biomed Pharmacother 2017; 95:
605-613.
- Linnemann AK, Baan M, Davis DB. Pancreatic β-cell
proliferation in obesity. Adv Nutr 2014; 5: 278-288.
- Sahin K, Orhan C, Akdemir F, et al. Mesozeaxanthin
protects the liver and reduces cardio-metabolic risk factors
in an insulin resistant rodent model. Food Nutr Res 2017;
61: 1353360.
- Peng J, He L. IRS posttranslational modifications in
regulating insulin signaling. J Mol Endocrinol 2018; 60: R1-
R8.
- Stolarczyk E, Le Gall M, Even P, et al. Loss of sugar
detection by GLUT2 affects glucose homeostasis in mice.
PLoS One 2007; 2: e1288.
- Thorens B, Mueckler M. Glucose transporters in the 21st
Century. Am J Physiol Endocrinol Metab 2010; 298: E141-
145.
- Chakraborty C, Doss CG, Bandyopadhyay S,
Agoramoorthy G. Influence of miRNA in insulin signaling
pathway and insulin resistance: Micro-molecules with a
major role in type-2 diabetes. Wiley Interdiscip Rev RNA
2014; 5: 697-712.
- Boden G. Free fatty acids-the link between obesity and
insulin resistance. Endocr Pract 2001; 7: 44-51.
- Saltiel AR, Kahn CR. Insulin signalling and the regulation
of glucose and lipid metabolism. Nature 2001; 414: 799-
806.
- Barakat G, Moustafa ME, Khalifeh I, et al. Effects of
exendin-4 and selenium on the expression of GLP-1R,
IRS-1, and preproinsulin in the pancreas of diabetic rats. J
Physiol Biochem 2016; 73: 387-394.
- Nadkarni P, Chepurny OG, Holz GG. Regulation of
glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci
2014; 121: 23-65.
- Janzen KM, Steuber TD, Nisly SA. GLP-1 agonists in type
1 diabetes mellitus. Ann Pharmacother 2016; 50: 656-665.
- Sreejayan N, Dong F, Kandadi MR, Yang X, Ren J.
Chromium alleviates glucose intolerance, insulin
resistance, and hepatic ER stress in obese mice. Obesity
(Silver Spring) 2008; 16: 1331-1337.
- Chen Y, Watson HM, Gao J, et al. Characterization of the
organic component of low-molecular-weight chromiumbinding
substance and its binding of chromium. J Nutr
2011; 141: 1225-1232.
- Sahin K, Tuzcu M, Orhan C, et al. The effects of chromium
picolinate and chromium histidinate administration on NFκB
and Nrf2/HO-1 pathway in the brain of diabetic rats.
Biol Trace Elem Res 2012; 150: 291-296.
- Gitoee A, Sadeghi G, Karimi A. Combination effects of
organic and ınorganic chromium on production
performance, reproductive response, ımmune status, and
maternal antibody transmission in breeder quails under
heat stress. Biol Trace Elem Res 2018; 184: 508-516.
- Vincent JB. New evidence against chromium as an
essential trace element. J Nutr. 2017; 147: 2212–2219.
- Vincent JB. The biochemistry of chromium. J Nutr 2000;
130: 715-718.
- Sharma I, Pati PK, Bhardwaj R. Effect of 28-
homobrassinolide on antioxidant defence system in
Raphanus sativus L. under chromium toxicity.
Ecotoxicology 2011; 20: 862-874.
- Tian H, Guo X, Wang X, et al. Chromium picolinate
supplementation for overweight or obese adults. Cochrane
Database Syst Rev 2013; 11: CD010063.
- Cathum S, Brown CE, Wong W. Determination of Cr3+
,CrO42-and Cr2O72-
in environmental matrixes by highperformance
liquid chromatography with diode-array
detection (HPLC-DAD). Anal Bioanal Chem 2002; 373:
103-110.
- Sahin K, Tuzcu M, Orhan C, et al. The effects of chromium
complex and level on glucose metabolism and memory
acquisition in rats fed high-fat diet. Biol Trace Elem Res
2011; 143: 1018-1030.
- Anderson RA, Polansky MM, Bryden NA. Stability and
absorption of chromium and absorption of chromium
histidinate complexes by humans. Biol Trace Elem Res
2004; 101: 211-218.
- Selcuk MY, Aygen B, Dogukan A, et al. Chromium
picolinate and chromium histidinate protects against renal
dysfunction by modulation of NF-κB pathway in high-fat
diet fed and Streptozotocin-induced diabetic rats. Nutr
Metab (Lond) 2012; 9: 30.
- Orhan C, Sahin N, Tuzcu Z, Komorowski JR, Sahin K.
Combined oral supplementation of chromium picolinate,
docosahexaenoic acid, and boron enhances
neuroprotection in rats fed a high-fat diet. Turk J Med Sci
2017; 47: 1616-1625.
- Gencoglu H, Tuzcu M, Hayirli A, Sahin K. Protective
effects of resveratrol against streptozotocin-induced
diabetes in rats by modulation of visfatin/sirtuin-1 pathway
and glucose transporters. Int J Food Sci Nutr 2015; 66:
314-320.
- Cohen J. Statistical Power Analysis for the Behavioral
Sciences. 2nd Edition, Lawrence Erlbaum Associates Inc.:
Hillsdale, NJ, USA: Hillsdale, NJ, USA, 1988.
- Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A
flexible statistical power analysis program for the social,
behavioral, and biomedical sciences. Behavior Research
Methods 2007; 39: 175-191.
- IBM SPSS, IBM Corp. Released 2013. IBM SPSS
Statistics for Windows, Version 22.0. Armonk, NY: USA.
- Petersen MC, Shulman GI. Mechanisms of insulin action
and ınsulin resistance. Physiol Rev 2018; 98: 2133-2223.
- Cefalu WT, Wang ZQ, Zhang XH, Baldor LC, Russell JC.
Oral chromium picolinate improves carbohydrate and lipid
metabolism and enhances skeletal muscle Glut-4
translocation in obese, hyperinsulinemic (JCR-LA
corpulent) rats. J Nutr 2002; 132: 1107-1114.
- Hua Y, Clark S, Ren J, Sreejayan N. Molecular
mechanisms of chromium in alleviating insulin resistance.
J Nutr Biochem 2012; 23: 313-319.
- Orhan C, Kucuk O, Tuzcu M, et al. Effect of supplementing
chromium histidinate and picolinate complexes along with
biotin on insulin sensitivity and related metabolic indices in
rats fed a high- fat diet. Food Sci Nutr 2018; 00: 1–12.
- Auberval N, Dal S, Maillard E, et al. Beneficial effects of a
red wine polyphenol extract on high-fat diet-induced
metabolic syndrome in rats. Eur J Nutr 2017; 56: 1467-
1475.
- Lan D, Xu N, Sun J, et al. Electroacupuncture mitigates
endothelial dysfunction via effects on the PI3K/Akt
signalling pathway in high fat diet-induced insulin-resistant
rats. Acupunct Med 2018; 36: 162-169.
- Salimi M, Zardooz H, Khodagholi F, Rostamkhani F,
Shaerzadeh F. High-fat diet with stress impaired islets'
insulin secretion by reducing plasma estradiol and
pancreatic GLUT2 protein levels in rats' proestrus phase. J
Physiol Pharmacol 2016; 67: 653-666.
- Adeghate E, Saeed Z, D'Souza C, et al. Effect of
nociceptin on insulin release in normal and diabetic rat
pancreas. Cell Tissue Res 2018; 374: 517-529.
- Wong JC, Vo V, Gorjala P, Fiscus RR. Pancreatic-β-cell
survival and proliferation are promoted by protein kinase G
type Iα and downstream regulation of AKT/FOXO1. Diab
Vasc Dis Res 2017; 14: 434-449.
- Ercin M, Sancar-Bas S, Bolkent S, Gezginci-Oktayoglu S.
Tub and β-catenin play a key role in insulin and leptin
resistance-induced pancreatic beta-cell differentiation.
Biochim Biophys Acta Mol Cell Res 2018; 1865: 1934-
1944.
- Turgut M, Cinar V, Pala R, et al. Biotin and chromium
histidinate improve glucose metabolism and proteins
expression levels of IRS-1, PPAR-γ, and NF-κB in
exercise-trained rats. J Int Soc Sports Nutr 2018; 15: 45.
- Araujo EP, Amaral ME, Filiputti E, et al. Restoration of
insulin secretion in pancreatic islets of protein-deficient
rats by reduced expression of insulin receptor substrate
(IRS)-1 and IRS-2. J Endocrinol 2004; 181: 25-38.
- Vasu S, Moffett RC, Thorens B, Flatt PR. Role of
endogenous GLP-1 and GIP in beta cell compensatory
responses to insulin resistance and cellular stress. PLoS
One 2014; 9: e101005.
- Machac N, Kaya Karasu G, Sahin N, et al. Effects of
supplementation of chromium histidinate on glucose, lipid
metabolism and oxidative stress in cats. J Anim Physiol
Anim Nutr (Berl) 2018: doi: 10.1111/jpn.13023.