Clinical characteristics of non-alcoholic fatty liver disease in Chinese adult hypopituitary patients
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摘要
BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease(NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospitalbetween August 2012 and April 2018. According to abdominal ultrasonography,these patients were divided into an NAFLD(-) group and an NAFLD(+) group,and the latter was further divided into an NAFLD group and a cirrhotic group.The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43(87.0%) of these patients exhibited growth hormone(GH) deficiency, and 39(78.3%) had diabetes insipidus. A total of 27(54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2 O and 151.0 mmol/L,respectively, which were significantly higher than those of the NAFLD patients(P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index(BMI)and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD(P = 0.011 and0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI(r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.
BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease(NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospitalbetween August 2012 and April 2018. According to abdominal ultrasonography,these patients were divided into an NAFLD(-) group and an NAFLD(+) group,and the latter was further divided into an NAFLD group and a cirrhotic group.The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43(87.0%) of these patients exhibited growth hormone(GH) deficiency, and 39(78.3%) had diabetes insipidus. A total of 27(54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2 O and 151.0 mmol/L,respectively, which were significantly higher than those of the NAFLD patients(P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index(BMI)and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD(P = 0.011 and0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI(r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.
BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease(NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospitalbetween August 2012 and April 2018. According to abdominal ultrasonography,these patients were divided into an NAFLD(-) group and an NAFLD(+) group,and the latter was further divided into an NAFLD group and a cirrhotic group.The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43(87.0%) of these patients exhibited growth hormone(GH) deficiency, and 39(78.3%) had diabetes insipidus. A total of 27(54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2 O and 151.0 mmol/L,respectively, which were significantly higher than those of the NAFLD patients(P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index(BMI)and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD(P = 0.011 and0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI(r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.
引文
1 National Guideline Centre(UK).2016[PMID:27441333]
2 Chalasani N,Younossi Z,Lavine JE,Charlton M,Cusi K,Rinella M,Harrison SA,Brunt EM,Sanyal AJ.The diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American Association for the Study of Liver Diseases.Hepatology 2018;67:328-357[PMID:28714183 DOI:10.1002/hep.29367]
3 Reccia I,Kumar J,Akladios C,Virdis F,Pai M,Habib N,Spalding D.Non-alcoholic fatty liver disease:Asign of systemic disease.Metabolism 2017;72:94-108[PMID:28641788 DOI:10.1016/j.metabol.2017.04.011]
4 Mittal S,El-Serag HB,Sada YH,Kanwal F,Duan Z,Temple S,May SB,Kramer JR,Richardson PA,Davila JA.Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.Clin Gastroenterol Hepatol 2016;14:124-131.e1[PMID:26196445 DOI:10.1016/j.cgh.2015.07.019]
5 Singal AG,El-Serag HB.Hepatocellular Carcinoma From Epidemiology to Prevention:Translating Knowledge into Practice.Clin Gastroenterol Hepatol 2015;13:2140-2151[PMID:26284591 DOI:10.1016/j.cgh.2015.08.014]
6 Buzzetti E,Pinzani M,Tsochatzis EA.The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD).Metabolism 2016;65:1038-1048[PMID:26823198 DOI:10.1016/j.metabol.2015.12.012]
7 Gardner CJ,Irwin AJ,Daousi C,McFarlane IA,Joseph F,Bell JD,Thomas EL,Adams VL,Kemp GJ,Cuthbertson DJ.Hepatic steatosis,GH deficiency and the effects of GH replacement:a Liverpool magnetic resonance spectroscopy study.Eur J Endocrinol 2012;166:993-1002[PMID:22433286 DOI:10.1530/EJE-12-0002]
8 Hong JW,Kim JY,Kim YE,Lee EJ.Metabolic parameters and nonalcoholic fatty liver disease in hypopituitary men.Horm Metab Res 2011;43:48-54[PMID:20865648 DOI:10.1055/s-0030-1265217]
9 Irie M,Itoh Y,Miyashita Y,Tsushima T,Shirai K.Complications in adults with growth hormone deficiency--a survey study in Japan.Endocr J 2004;51:479-485[PMID:15516782]
10 Adams LA,Feldstein A,Lindor KD,Angulo P.Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction.Hepatology 2004;39:909-914[PMID:15057893 DOI:10.1002/hep.20140]
11 Matsumoto R,Fukuoka H,Iguchi G,Nishizawa H,Bando H,Suda K,Takahashi M,Takahashi Y.Longterm effects of growth hormone replacement therapy on liver function in adult patients with growth hormone deficiency.Growth Horm IGF Res 2014;24:174-179[PMID:25116471 DOI:10.1016/j.ghir.2014.07.002]
12 Nakajima K,Hashimoto E,Kaneda H,Tokushige K,Shiratori K,Hizuka N,Takano K.Pediatric nonalcoholic steatohepatitis associated with hypopituitarism.J Gastroenterol 2005;40:312-315[PMID:15830293 DOI:10.1007/s00535-004-1541-4]
13 Jonas MM,Krawczuk LE,Kim HB,Lillehei C,Perez-Atayde A.Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and hepatopulmonary syndrome.Liver Transpl 2005;11:108-110[PMID:15690545 DOI:10.1002/lt.20332]
14 Ursula Kaiser KKYH,Melmed S,Polonsky KS,Larsen PR,Kronenberg HM.Pituitary Physiology and Diagnostic Evaluation.Melmed S,Polonsky KS,Larsen PR,Kronenberg HM.Williams Textbook Of Endocrinology,13th ed.Canada:Patricia Tannian 2015;182-214
15 Bhasin S,Cunningham GR,Hayes FJ,Matsumoto AM,Snyder PJ,Swerdloff RS,Montori VM;Task Force,Endocrine Society.Testosterone therapy in men with androgen deficiency syndromes:an Endocrine Society clinical practice guideline.J Clin Endocrinol Metab 2010;95:2536-2559[PMID:20525905 DOI:10.1210/jc.2009-2354]
16 Mao JF,Xu HL,Duan J,Chen RR,Li L,Li B,Nie M,Min L,Zhang HB,Wu XY.Reversal of idiopathic hypogonadotropic hypogonadism:a cohort study in Chinese patients.Asian J Androl 2015;17:497-502[PMID:25578938 DOI:10.4103/1008-682X.145072]
17 Sherlock M,Reulen RC,Alonso AA,Ayuk J,Clayton RN,Sheppard MC,Hawkins MM,Bates AS,Stewart PM.ACTH deficiency,higher doses of hydrocortisone replacement,and radiotherapy are independent predictors of mortality in patients with acromegaly.J Clin Endocrinol Metab 2009;94:4216-4223[PMID:19808848 DOI:10.1210/jc.2009-1097]
18 Alan G,Robinson JGV.Posterior Pituitary.In:Melmed S,Polonsky KS,Larsen PR,Kronenberg HM,editor.Williams Textbook of Endocrinology.13th ed.Canada:Patricia Tannian 2015;300-313
19 Fan JG.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China.J Gastroenterol Hepatol2013;28 Suppl 1:11-17[PMID:23855290 DOI:10.1111/jgh.12036]
20 Kabbany MN,Conjeevaram Selvakumar PK,Watt K,Lopez R,Akras Z,Zein N,Carey W,Alkhouri N.Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States:An Analysis of National Health and Nutrition Examination Survey Data.Am J Gastroenterol 2017;112:581-587[PMID:28195177 DOI:10.1038/ajg.2017.5]
21 Hoffmann A,Müller HL.RETRACTION Novel perspectives on hypothalamic-pituitary dysfunction as a risk factor for non-alcoholic fatty liver disease.Minerva Endocrinol 2017;42:132-144[PMID:27405476DOI:10.23736/S0391-1977.16.02500-1]
22 Schliess F,H?ussinger D.Osmosensing and signaling in the regulation of liver function.Contrib Nephrol2006;152:198-209[PMID:17065813 DOI:10.1159/000096324]
23 Reinehr R,Becker S,H?ngen A,Haüssinger D.The Src family kinase Yes triggers hyperosmotic activation of the epidermal growth factor receptor and CD95.J Biol Chem 2004;279:23977-23987[PMID:15039424 DOI:10.1074/jbc.M401519200]
24 Reinehr R,Schliess F,H?ussinger D.Hyperosmolarity and CD95L trigger CD95/EGF receptor association and tyrosine phosphorylation of CD95 as prerequisites for CD95 membrane trafficking and DISC formation.FASEB J 2003;17:731-733[PMID:12586732 DOI:10.1096/fj.02-0915fje]
25 Meier R,Thelen M,Hemmings BA.Inactivation and dephosphorylation of protein kinase Balpha(PKBalpha)promoted by hyperosmotic stress.EMBO J 1998;17:7294-7303[PMID:9857186 DOI:10.1093/emboj/17.24.7294]
26 Chen D,Elmendorf JS,Olson AL,Li X,Earp HS,Pessin JE.Osmotic shock stimulates GLUT4translocation in 3T3L1 adipocytes by a novel tyrosine kinase pathway.J Biol Chem 1997;272:27401-27410[PMID:9341192]
27 Randhawa VK,Thong FS,Lim DY,Li D,Garg RR,Rudge R,Galli T,Rudich A,Klip A.Insulin and hypertonicity recruit GLUT4 to the plasma membrane of muscle cells by using N-ethylmaleimide-sensitive factor-dependent SNARE mechanisms but different v-SNAREs:role of TI-VAMP.Mol Biol Cell 2004;15:5565-5573[PMID:15469990 DOI:10.1091/mbc.e04-03-0266]
28 Gual P,Gonzalez T,Grémeaux T,Barres R,Le Marchand-Brustel Y,Tanti JF.Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes.J Biol Chem2003;278:26550-26557[PMID:12730242 DOI:10.1074/jbc.M212273200]
29 Ercin CN,Dogru T,Genc H,Celebi G,Aslan F,Gurel H,Kara M,Sertoglu E,Tapan S,Bagci S,Rizzo M,Sonmez A.Insulin Resistance but Not Visceral Adiposity Index Is Associated with Liver Fibrosis in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease.Metab Syndr Relat Disord 2015;13:319-325[PMID:26011302 DOI:10.1089/met.2015.0018]
30 Kumar R.Hepatogenous Diabetes:An Underestimated Problem of Liver Cirrhosis.Indian J Endocrinol Metab 2018;22:552-559[PMID:30148106 DOI:10.4103/ijem.IJEM_79_18]
31 Orsi E,Grancini V,Menini S,Aghemo A,Pugliese G.Hepatogenous diabetes:Is it time to separate it from type 2 diabetes?Liver Int 2017;37:950-962[PMID:27943508 DOI:10.1111/liv.13337]
32 Esterson YB,Grimaldi GM.Radiologic Imaging in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.Clin Liver Dis 2018;22:93-108[PMID:29128063 DOI:10.1016/j.cld.2017.08.005]
2 Chalasani N,Younossi Z,Lavine JE,Charlton M,Cusi K,Rinella M,Harrison SA,Brunt EM,Sanyal AJ.The diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American Association for the Study of Liver Diseases.Hepatology 2018;67:328-357[PMID:28714183 DOI:10.1002/hep.29367]
3 Reccia I,Kumar J,Akladios C,Virdis F,Pai M,Habib N,Spalding D.Non-alcoholic fatty liver disease:Asign of systemic disease.Metabolism 2017;72:94-108[PMID:28641788 DOI:10.1016/j.metabol.2017.04.011]
4 Mittal S,El-Serag HB,Sada YH,Kanwal F,Duan Z,Temple S,May SB,Kramer JR,Richardson PA,Davila JA.Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.Clin Gastroenterol Hepatol 2016;14:124-131.e1[PMID:26196445 DOI:10.1016/j.cgh.2015.07.019]
5 Singal AG,El-Serag HB.Hepatocellular Carcinoma From Epidemiology to Prevention:Translating Knowledge into Practice.Clin Gastroenterol Hepatol 2015;13:2140-2151[PMID:26284591 DOI:10.1016/j.cgh.2015.08.014]
6 Buzzetti E,Pinzani M,Tsochatzis EA.The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD).Metabolism 2016;65:1038-1048[PMID:26823198 DOI:10.1016/j.metabol.2015.12.012]
7 Gardner CJ,Irwin AJ,Daousi C,McFarlane IA,Joseph F,Bell JD,Thomas EL,Adams VL,Kemp GJ,Cuthbertson DJ.Hepatic steatosis,GH deficiency and the effects of GH replacement:a Liverpool magnetic resonance spectroscopy study.Eur J Endocrinol 2012;166:993-1002[PMID:22433286 DOI:10.1530/EJE-12-0002]
8 Hong JW,Kim JY,Kim YE,Lee EJ.Metabolic parameters and nonalcoholic fatty liver disease in hypopituitary men.Horm Metab Res 2011;43:48-54[PMID:20865648 DOI:10.1055/s-0030-1265217]
9 Irie M,Itoh Y,Miyashita Y,Tsushima T,Shirai K.Complications in adults with growth hormone deficiency--a survey study in Japan.Endocr J 2004;51:479-485[PMID:15516782]
10 Adams LA,Feldstein A,Lindor KD,Angulo P.Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction.Hepatology 2004;39:909-914[PMID:15057893 DOI:10.1002/hep.20140]
11 Matsumoto R,Fukuoka H,Iguchi G,Nishizawa H,Bando H,Suda K,Takahashi M,Takahashi Y.Longterm effects of growth hormone replacement therapy on liver function in adult patients with growth hormone deficiency.Growth Horm IGF Res 2014;24:174-179[PMID:25116471 DOI:10.1016/j.ghir.2014.07.002]
12 Nakajima K,Hashimoto E,Kaneda H,Tokushige K,Shiratori K,Hizuka N,Takano K.Pediatric nonalcoholic steatohepatitis associated with hypopituitarism.J Gastroenterol 2005;40:312-315[PMID:15830293 DOI:10.1007/s00535-004-1541-4]
13 Jonas MM,Krawczuk LE,Kim HB,Lillehei C,Perez-Atayde A.Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and hepatopulmonary syndrome.Liver Transpl 2005;11:108-110[PMID:15690545 DOI:10.1002/lt.20332]
14 Ursula Kaiser KKYH,Melmed S,Polonsky KS,Larsen PR,Kronenberg HM.Pituitary Physiology and Diagnostic Evaluation.Melmed S,Polonsky KS,Larsen PR,Kronenberg HM.Williams Textbook Of Endocrinology,13th ed.Canada:Patricia Tannian 2015;182-214
15 Bhasin S,Cunningham GR,Hayes FJ,Matsumoto AM,Snyder PJ,Swerdloff RS,Montori VM;Task Force,Endocrine Society.Testosterone therapy in men with androgen deficiency syndromes:an Endocrine Society clinical practice guideline.J Clin Endocrinol Metab 2010;95:2536-2559[PMID:20525905 DOI:10.1210/jc.2009-2354]
16 Mao JF,Xu HL,Duan J,Chen RR,Li L,Li B,Nie M,Min L,Zhang HB,Wu XY.Reversal of idiopathic hypogonadotropic hypogonadism:a cohort study in Chinese patients.Asian J Androl 2015;17:497-502[PMID:25578938 DOI:10.4103/1008-682X.145072]
17 Sherlock M,Reulen RC,Alonso AA,Ayuk J,Clayton RN,Sheppard MC,Hawkins MM,Bates AS,Stewart PM.ACTH deficiency,higher doses of hydrocortisone replacement,and radiotherapy are independent predictors of mortality in patients with acromegaly.J Clin Endocrinol Metab 2009;94:4216-4223[PMID:19808848 DOI:10.1210/jc.2009-1097]
18 Alan G,Robinson JGV.Posterior Pituitary.In:Melmed S,Polonsky KS,Larsen PR,Kronenberg HM,editor.Williams Textbook of Endocrinology.13th ed.Canada:Patricia Tannian 2015;300-313
19 Fan JG.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China.J Gastroenterol Hepatol2013;28 Suppl 1:11-17[PMID:23855290 DOI:10.1111/jgh.12036]
20 Kabbany MN,Conjeevaram Selvakumar PK,Watt K,Lopez R,Akras Z,Zein N,Carey W,Alkhouri N.Prevalence of Nonalcoholic Steatohepatitis-Associated Cirrhosis in the United States:An Analysis of National Health and Nutrition Examination Survey Data.Am J Gastroenterol 2017;112:581-587[PMID:28195177 DOI:10.1038/ajg.2017.5]
21 Hoffmann A,Müller HL.RETRACTION Novel perspectives on hypothalamic-pituitary dysfunction as a risk factor for non-alcoholic fatty liver disease.Minerva Endocrinol 2017;42:132-144[PMID:27405476DOI:10.23736/S0391-1977.16.02500-1]
22 Schliess F,H?ussinger D.Osmosensing and signaling in the regulation of liver function.Contrib Nephrol2006;152:198-209[PMID:17065813 DOI:10.1159/000096324]
23 Reinehr R,Becker S,H?ngen A,Haüssinger D.The Src family kinase Yes triggers hyperosmotic activation of the epidermal growth factor receptor and CD95.J Biol Chem 2004;279:23977-23987[PMID:15039424 DOI:10.1074/jbc.M401519200]
24 Reinehr R,Schliess F,H?ussinger D.Hyperosmolarity and CD95L trigger CD95/EGF receptor association and tyrosine phosphorylation of CD95 as prerequisites for CD95 membrane trafficking and DISC formation.FASEB J 2003;17:731-733[PMID:12586732 DOI:10.1096/fj.02-0915fje]
25 Meier R,Thelen M,Hemmings BA.Inactivation and dephosphorylation of protein kinase Balpha(PKBalpha)promoted by hyperosmotic stress.EMBO J 1998;17:7294-7303[PMID:9857186 DOI:10.1093/emboj/17.24.7294]
26 Chen D,Elmendorf JS,Olson AL,Li X,Earp HS,Pessin JE.Osmotic shock stimulates GLUT4translocation in 3T3L1 adipocytes by a novel tyrosine kinase pathway.J Biol Chem 1997;272:27401-27410[PMID:9341192]
27 Randhawa VK,Thong FS,Lim DY,Li D,Garg RR,Rudge R,Galli T,Rudich A,Klip A.Insulin and hypertonicity recruit GLUT4 to the plasma membrane of muscle cells by using N-ethylmaleimide-sensitive factor-dependent SNARE mechanisms but different v-SNAREs:role of TI-VAMP.Mol Biol Cell 2004;15:5565-5573[PMID:15469990 DOI:10.1091/mbc.e04-03-0266]
28 Gual P,Gonzalez T,Grémeaux T,Barres R,Le Marchand-Brustel Y,Tanti JF.Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes.J Biol Chem2003;278:26550-26557[PMID:12730242 DOI:10.1074/jbc.M212273200]
29 Ercin CN,Dogru T,Genc H,Celebi G,Aslan F,Gurel H,Kara M,Sertoglu E,Tapan S,Bagci S,Rizzo M,Sonmez A.Insulin Resistance but Not Visceral Adiposity Index Is Associated with Liver Fibrosis in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease.Metab Syndr Relat Disord 2015;13:319-325[PMID:26011302 DOI:10.1089/met.2015.0018]
30 Kumar R.Hepatogenous Diabetes:An Underestimated Problem of Liver Cirrhosis.Indian J Endocrinol Metab 2018;22:552-559[PMID:30148106 DOI:10.4103/ijem.IJEM_79_18]
31 Orsi E,Grancini V,Menini S,Aghemo A,Pugliese G.Hepatogenous diabetes:Is it time to separate it from type 2 diabetes?Liver Int 2017;37:950-962[PMID:27943508 DOI:10.1111/liv.13337]
32 Esterson YB,Grimaldi GM.Radiologic Imaging in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.Clin Liver Dis 2018;22:93-108[PMID:29128063 DOI:10.1016/j.cld.2017.08.005]