Araştırma Makalesi
The effects of oral antidiabetics on adipogenesis related gene expressions in 3T3-L1, AML12 cell lines and their co-cultures
Öz
The objective of the study was investigated
for the effects of oral antidiabetic drugs, how they effect the cells
proliferation activities and how they change the expressions of FTO, CD68,
NIBAN, and RAN genes which could change insulin signalization and also be
effective in the adipogenetic process on 3T3-L1 adipocytes, AML12 hepatocytes
and adipocyte-hepatocyte co-cultures. Cell proliferation was examined real time with iCELLigence system
and measured for 96 hours each 15 min period. The time and amount of active
substances of the oral anti-diabetic drugs which were applied to cells were
determined real time according to IC50 value. FTO, CD68 NIBAN and RAN gene
expression profiles were determined with qPCR. When single and multiple doses
of glipizide and acarbose in co-culture’s were compared respectively, the 24
hour IC50 values were determined as 180 μM and 17 mg/ml in adipocytes; 72 μM
and 23 mg/ml in hepatocytes, 41.5 μM and 5 mg/ml in coculture cells. The
application of metformin for 24 hour IC50 value in single culture was
determined as 175 mM in adipocytes and 2.3 mM in hepatocytes. In the Metformin
administered cells. FTO, CD68 and NIBAN gene expressions were decreased in all
groups. In the acarbose applied cells FTO and CD68 gene expressions were
decreased in all groups. In the acarbose applied cells while NIBAN gene
expression was decreased in adipocytes, it was fund to increase in co-cultured
adipocytes. In the acarbose applied cells RAN gene expression was found to
increase in all groups. Decreasing effects of antidiabetics on CD68 and FTO
expressions may show protective effect of drug on inflammation and obesity. In conclusion, oral
antidiabetic drug use may be effective in development glucose homeostasis via
changing the gene expression of RAN in hepatocytes and adipocytes, this pathway
may have therapeutic effect and provide novel strategies for treatment of
insulin resistance.
Anahtar Kelimeler
3T3-L1 adipocyte AML12 hepatocyte iCELLigence system oral antidiabetics non-alcholic fatty liver disease gene expression
Destekleyen Kurum
Marmara University Scientific Research Projects Commission
Proje Numarası
FEN-C-DRP-131113-0433
Kaynakça
- Adachi H, Majima S, Kon S, Kobayashi T, Kajino K, Mitani H, Hirayama Y, Shiina H, Igawa M., Hino O 2004. Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis. Oncogene, 23(19), 3495-3500.
- American Diabetes Association 2018. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2018. Diabetes Care, 41, 13-27.
- Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM 2005. IKK-b links inflammation to obesity-induced insulin resistance. Nat Med 11: 191–197.
- Beyler AR, Aytaç Ş 2002. Nonalkolik Steatohepatitis. Gastroenteroloji, 593-600.
- Bloodworth JMB, Hamwi GJ 1961. Histopathologic lesion associated with sulfonylurea administration. Diabetes, 10: 90-99.
- Bravard A, Veilleux A, Disse E, Laville M, Vidal H, Tchernof A, Rieusset J 2013. The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity. Obesity (Silver Spring), 21, 1165–1173.
- Cai DS, Yuan MS, Frantz DF, Melendez PA, Hansen L, Lee J 2005. Local and systemic insulin resistance resulting from hepatic activation of IKK-b and NF-jB. Nat Med, 11: 183–190.
- Cancello R1, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumié A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clément K 2005. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes, 54, 2277-2286.
- Clarke, PR. Zhang, C 2008. Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol, 9, 464–477.
- Clément K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, Sicard A, Rome S, Benis A, Zucker JD, Vidal H, Laville M, Barsh GS, Basdevant A, Stich V,
- Cancello R, Langin D 2004. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. The FASEB Journal 18, 1657-1669.
- Demir, K 2004. Nonalkolik Yağlı Karaciğer Hastalığı:Etyoloji ve patogenez. Çapa Gastroenteroloji Günleri, 90-94.
- Di Gregorio GB, Yao-Borengasser A, Rasouli N, Varma V, Lu T, Miles LM, Ranganathan G, Peterson CA, McGehee RE, Kern PA 2005. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes, 54(8): 2305-2313.
- Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-
- Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P 2007. Variation in FTO contributes to childhood obesity and severe adult obesity. Nature Genetic 39, 724-726.
- Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI 2007. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894.
- Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O'Doherty RM 2010. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes, 59(2): 347-57.
- Kim SP, Ellmerer M, Van Citters GW, Bergman RN 2003. Primary of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog. Diabetes, 52: 2453–2460.
- Koldemir M, Kahveci C, Bayer H, Cagatay P, Yildiz S, Bagriacik N, Susleyici-Duman B 2012. Relationship of RIC-3 gene rs1528133 polymorphism with varying degrees of body weight and eating behavior. Diabetes Metab Syndr. 6(2):90-95.
- Melnik BC 2015. Milk: an epigenetic amplifier of FTO‑mediated transcription? Implications for Western diseases. Melnik J Transl Med, 13: 385.
- Miard S, Dombrowski L, Carte, S, Boivin L, Picard F 2008. Aging alters PPARgamma in rodent and human adipose tissue by modulating the balance in steroid receptor coactivator-1. Aging Cell, 8(4):449-459.
- McCarthy MI 2010. Genomics, type 2 diabetes, and obesity. N Engl J Med, 363(24), 2339-2350.
- Niu L, Geyer PE, Wewer Albrechtsen NJ, Gluud LL, Santos A, Doll S, Treit PV, Holst JJ, Knop FK, Vilsbøll T, Junker A, Sachs S, Stemmer K, Müller TD, Tschöp MH,
- Hofmann SM, Mann M 2019. Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease. Mol Syst Biol. 1;15(3):e8793.
- Prokopenko I, McCarthy MI, Lindgren CM 2008. Type 2 diabetes: new genes, new understanding. Trends in Genetics 24, 613-621.
- Reaven GM 1995. Pathophysiology of insulin resistance in human disease. Physiol Rev 75, 473-486.
- Rösen P, Nawroth PP, King G, Möller W, Tritschler HJ, Packer L 2001. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCOMCBN, the American Diabetes Association and the German Diabetes Society. Diabetes/Metabolism Research and Reviews 17, 189–212.
- Rudovich NN, Weickert MO, Andreas JM, Pfeiffer FH 2010. Combination of acarbose and ezetimibe prevents non-alcoholic fatty liver disease: A break of intestinal insulin resistance? Journal of Hepatology, 52(6): 952-953.
- Samaras K, Botelho NK, Chisholm DJ, Lord RV 2010. Subcutaneous and Visceral Adipose Tissue FTO Gene Expression and Adiposity, Insulin Action, Glucose Metabolism, and Inflammatory Adipokines in Type 2 Diabetes Mellitus and in Health. Obesity Surgery 20, pp.108-113.
- Sanyal AJ 2003. Nonalcoholic fatty liver and steatohepatitis: the hepatic manifestation of the insulin resistance syndrome. Presented at The First Annual World Congress on the Insulin Resistance Syndrome. November 20-22 Los Angeles, California.
- Sazer S, Dasso M 2000. The ran decathlon: multiple roles of Ran. J Cell Sci, 113(7): 1111–1118.Schlessinger D, Cao A, Lakatta E, Abecasis GR 2007. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genetic 3, e115.
- Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Segev N 2011. Coordination of intracellular transport steps by GTPases. Sem Cell Dev Biol, 22, 33–38.
- Shoelson SE, Lee J, Goldfine AB 2006. Inflammation and insulin resistance. J Clin Invest, 116, 1793–1801.
- Stratigopoulos G, Padilla SL, LeDuc CA, Watson E, Hattersley AT, McCarthy MI, Zeltser LM, Chung WK, Leibel RL 2008. Regulation of Fto/Ftm gene expression in mice and humans. American Journal of Physiology – Regulatory. Integrative and Comparative Physiology, 294, 1185–1196.
- Sulkin TV, Bosman D, Krentz AJ 1997. Contraindications to metformin therapy in patients with NIDDM. Diabetes Care, 20: 925-928.
- Sun GD, Kobayashi T, Abe M, Tada N, Adachi H, Shiota A, Totsuka Y, Hino O 2007. The endoplasmic reticulum stress-inducible protein Niban regulates eIF2α and S6K1/4E-BP1 phosphorylation. Biochem Biophys Res Commun, 360, 181–187.
- Taniguchi CM, Ueki K, Kahn R 2005. Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. J Clin Invest, 115: 718–727.
- Tolman KG, Fonseca V, Pharmd AD, Tan MH 2007. Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease. Diabetes Care, 30 (3).
- Tükün A 2008. Diyabette Genetik Yükler. Türk Biyokimya Dergisi 33.
- Vasanth Rao VRB, Candasamy M, Bhattamisra SK 2019. Obesity an overview: Genetic conditions and recent developments in therapeutic interventions. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13, 2112-2120.
- Wang Z, Lv J, Zhang R, Zhu Y, Zhu D, Sun Y, Zhu, J, Han X 2006. Co-culture with fat cells induces cellular insulin resistance in primary hepatocytes. Biochem Biophys Res Commun, 345(3): 976-83.
- Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr 2003. Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation, 112, 1796-1808.
- Wellen KE and Hotamisligil GS 2005. Inflammation, stress, and diabetes. J Clin Invest, 115, 1111–1119.
- Xia F, Dohi T, Martin NM, Raskett CM, Liu Q, Altieri DC 2011. Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development. PLoS ONE 6(11), pp. e27879.
- Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest, 112: 1821–1830.
- Yaribeygi H, Simental-Mendía LE, Barreto GE, Sahebkar A 2019. Metabolic effects of antidiabetic drugs on adipocytes and adipokine expression. J Cell Physiol, 1-11.
- Ye F, Zhang H, Yang YX, Hu HD, Sze SK, Meng W, Qian J, Ren H, Yang BL, Luo MY, Wu X, Zhu W, Cai WJ, Tong JB 2011. Comparative Proteome Analysis of 3T3-L1 Adipocyte Differentiation Using iTRAQ-Coupled 2D LC-MS/MS. Journal of Cellular Biochemistry, 112, 3002– 3017
- Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R 2016. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology, 64: 1577 – 1586.
- Yuzbashian E, Asghari G, Hedayati M, Zarkesh M, Mirmiran P, Khalaj A 2019. The association of dietary carbohydrate with FTO gene expression in visceral and subcutaneous adipose tissue of adults without diabetes. Nutrition, 63-64:92-97.
- Yudin D, Fainzilber M 2009. Ran on tracks-cytoplasmic roles for a nuclear regulator. J Cell Sci, 122, 587-593.
- Zhou L, Sell H, Eckardt K, Yang Z, Eckel J 2007. Conditioned medium obtained from in vitro differentiated adipocytes and resistin induce insulin resistance in human hepatocytes. FEBS Lett, 581(22): 4303-4308.
- Zulian A, Cancello R, Girola A, Gilardini L, Alberti L, Croci M, Micheletto G, Danelli P, Invitti C 2011. In vitro and in vivo effects of metformin on human adipose tissue adiponectin. Obes Facts, 4(1):27-33.
Yıl 2019,
Cilt: 2 Sayı: 1, 29 - 37, 20.07.2019
Öz
Proje Numarası
FEN-C-DRP-131113-0433
Kaynakça
- Adachi H, Majima S, Kon S, Kobayashi T, Kajino K, Mitani H, Hirayama Y, Shiina H, Igawa M., Hino O 2004. Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis. Oncogene, 23(19), 3495-3500.
- American Diabetes Association 2018. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2018. Diabetes Care, 41, 13-27.
- Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM 2005. IKK-b links inflammation to obesity-induced insulin resistance. Nat Med 11: 191–197.
- Beyler AR, Aytaç Ş 2002. Nonalkolik Steatohepatitis. Gastroenteroloji, 593-600.
- Bloodworth JMB, Hamwi GJ 1961. Histopathologic lesion associated with sulfonylurea administration. Diabetes, 10: 90-99.
- Bravard A, Veilleux A, Disse E, Laville M, Vidal H, Tchernof A, Rieusset J 2013. The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity. Obesity (Silver Spring), 21, 1165–1173.
- Cai DS, Yuan MS, Frantz DF, Melendez PA, Hansen L, Lee J 2005. Local and systemic insulin resistance resulting from hepatic activation of IKK-b and NF-jB. Nat Med, 11: 183–190.
- Cancello R1, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumié A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clément K 2005. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes, 54, 2277-2286.
- Clarke, PR. Zhang, C 2008. Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol, 9, 464–477.
- Clément K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, Sicard A, Rome S, Benis A, Zucker JD, Vidal H, Laville M, Barsh GS, Basdevant A, Stich V,
- Cancello R, Langin D 2004. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. The FASEB Journal 18, 1657-1669.
- Demir, K 2004. Nonalkolik Yağlı Karaciğer Hastalığı:Etyoloji ve patogenez. Çapa Gastroenteroloji Günleri, 90-94.
- Di Gregorio GB, Yao-Borengasser A, Rasouli N, Varma V, Lu T, Miles LM, Ranganathan G, Peterson CA, McGehee RE, Kern PA 2005. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes, 54(8): 2305-2313.
- Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-
- Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P 2007. Variation in FTO contributes to childhood obesity and severe adult obesity. Nature Genetic 39, 724-726.
- Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI 2007. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894.
- Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O'Doherty RM 2010. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes, 59(2): 347-57.
- Kim SP, Ellmerer M, Van Citters GW, Bergman RN 2003. Primary of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog. Diabetes, 52: 2453–2460.
- Koldemir M, Kahveci C, Bayer H, Cagatay P, Yildiz S, Bagriacik N, Susleyici-Duman B 2012. Relationship of RIC-3 gene rs1528133 polymorphism with varying degrees of body weight and eating behavior. Diabetes Metab Syndr. 6(2):90-95.
- Melnik BC 2015. Milk: an epigenetic amplifier of FTO‑mediated transcription? Implications for Western diseases. Melnik J Transl Med, 13: 385.
- Miard S, Dombrowski L, Carte, S, Boivin L, Picard F 2008. Aging alters PPARgamma in rodent and human adipose tissue by modulating the balance in steroid receptor coactivator-1. Aging Cell, 8(4):449-459.
- McCarthy MI 2010. Genomics, type 2 diabetes, and obesity. N Engl J Med, 363(24), 2339-2350.
- Niu L, Geyer PE, Wewer Albrechtsen NJ, Gluud LL, Santos A, Doll S, Treit PV, Holst JJ, Knop FK, Vilsbøll T, Junker A, Sachs S, Stemmer K, Müller TD, Tschöp MH,
- Hofmann SM, Mann M 2019. Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease. Mol Syst Biol. 1;15(3):e8793.
- Prokopenko I, McCarthy MI, Lindgren CM 2008. Type 2 diabetes: new genes, new understanding. Trends in Genetics 24, 613-621.
- Reaven GM 1995. Pathophysiology of insulin resistance in human disease. Physiol Rev 75, 473-486.
- Rösen P, Nawroth PP, King G, Möller W, Tritschler HJ, Packer L 2001. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCOMCBN, the American Diabetes Association and the German Diabetes Society. Diabetes/Metabolism Research and Reviews 17, 189–212.
- Rudovich NN, Weickert MO, Andreas JM, Pfeiffer FH 2010. Combination of acarbose and ezetimibe prevents non-alcoholic fatty liver disease: A break of intestinal insulin resistance? Journal of Hepatology, 52(6): 952-953.
- Samaras K, Botelho NK, Chisholm DJ, Lord RV 2010. Subcutaneous and Visceral Adipose Tissue FTO Gene Expression and Adiposity, Insulin Action, Glucose Metabolism, and Inflammatory Adipokines in Type 2 Diabetes Mellitus and in Health. Obesity Surgery 20, pp.108-113.
- Sanyal AJ 2003. Nonalcoholic fatty liver and steatohepatitis: the hepatic manifestation of the insulin resistance syndrome. Presented at The First Annual World Congress on the Insulin Resistance Syndrome. November 20-22 Los Angeles, California.
- Sazer S, Dasso M 2000. The ran decathlon: multiple roles of Ran. J Cell Sci, 113(7): 1111–1118.Schlessinger D, Cao A, Lakatta E, Abecasis GR 2007. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genetic 3, e115.
- Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Segev N 2011. Coordination of intracellular transport steps by GTPases. Sem Cell Dev Biol, 22, 33–38.
- Shoelson SE, Lee J, Goldfine AB 2006. Inflammation and insulin resistance. J Clin Invest, 116, 1793–1801.
- Stratigopoulos G, Padilla SL, LeDuc CA, Watson E, Hattersley AT, McCarthy MI, Zeltser LM, Chung WK, Leibel RL 2008. Regulation of Fto/Ftm gene expression in mice and humans. American Journal of Physiology – Regulatory. Integrative and Comparative Physiology, 294, 1185–1196.
- Sulkin TV, Bosman D, Krentz AJ 1997. Contraindications to metformin therapy in patients with NIDDM. Diabetes Care, 20: 925-928.
- Sun GD, Kobayashi T, Abe M, Tada N, Adachi H, Shiota A, Totsuka Y, Hino O 2007. The endoplasmic reticulum stress-inducible protein Niban regulates eIF2α and S6K1/4E-BP1 phosphorylation. Biochem Biophys Res Commun, 360, 181–187.
- Taniguchi CM, Ueki K, Kahn R 2005. Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. J Clin Invest, 115: 718–727.
- Tolman KG, Fonseca V, Pharmd AD, Tan MH 2007. Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease. Diabetes Care, 30 (3).
- Tükün A 2008. Diyabette Genetik Yükler. Türk Biyokimya Dergisi 33.
- Vasanth Rao VRB, Candasamy M, Bhattamisra SK 2019. Obesity an overview: Genetic conditions and recent developments in therapeutic interventions. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13, 2112-2120.
- Wang Z, Lv J, Zhang R, Zhu Y, Zhu D, Sun Y, Zhu, J, Han X 2006. Co-culture with fat cells induces cellular insulin resistance in primary hepatocytes. Biochem Biophys Res Commun, 345(3): 976-83.
- Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr 2003. Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation, 112, 1796-1808.
- Wellen KE and Hotamisligil GS 2005. Inflammation, stress, and diabetes. J Clin Invest, 115, 1111–1119.
- Xia F, Dohi T, Martin NM, Raskett CM, Liu Q, Altieri DC 2011. Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development. PLoS ONE 6(11), pp. e27879.
- Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest, 112: 1821–1830.
- Yaribeygi H, Simental-Mendía LE, Barreto GE, Sahebkar A 2019. Metabolic effects of antidiabetic drugs on adipocytes and adipokine expression. J Cell Physiol, 1-11.
- Ye F, Zhang H, Yang YX, Hu HD, Sze SK, Meng W, Qian J, Ren H, Yang BL, Luo MY, Wu X, Zhu W, Cai WJ, Tong JB 2011. Comparative Proteome Analysis of 3T3-L1 Adipocyte Differentiation Using iTRAQ-Coupled 2D LC-MS/MS. Journal of Cellular Biochemistry, 112, 3002– 3017
- Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R 2016. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology, 64: 1577 – 1586.
- Yuzbashian E, Asghari G, Hedayati M, Zarkesh M, Mirmiran P, Khalaj A 2019. The association of dietary carbohydrate with FTO gene expression in visceral and subcutaneous adipose tissue of adults without diabetes. Nutrition, 63-64:92-97.
- Yudin D, Fainzilber M 2009. Ran on tracks-cytoplasmic roles for a nuclear regulator. J Cell Sci, 122, 587-593.
- Zhou L, Sell H, Eckardt K, Yang Z, Eckel J 2007. Conditioned medium obtained from in vitro differentiated adipocytes and resistin induce insulin resistance in human hepatocytes. FEBS Lett, 581(22): 4303-4308.
- Zulian A, Cancello R, Girola A, Gilardini L, Alberti L, Croci M, Micheletto G, Danelli P, Invitti C 2011. In vitro and in vivo effects of metformin on human adipose tissue adiponectin. Obes Facts, 4(1):27-33.
Toplam 52 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Yapısal Biyoloji |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | FEN-C-DRP-131113-0433 |
| Yayımlanma Tarihi | 20 Temmuz 2019 |
| Kabul Tarihi | 20 Temmuz 2019 |
| Yayımlandığı Sayı | Yıl 2019 Cilt: 2 Sayı: 1 |
Kaynak Göster
