Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10-year prospective study

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent stimulator of DNA synthesis in a variety of epithelial cells, including hepatocytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma concentrations of HGF/SF that are achieved during intraperitoneal infusion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in liver wet weight. Mitotic figures were rarely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglycerides, cholesterol, total protein, and albumin were also dose dependently increased, whereas alkaline phosphatase was reduced. From these data we conclude 1) that combining HGF/SF with dextran sulfate provides a novel method for delivering HGF/SF in a continuous manner, 2) that HGF/SF can induce liver growth in an intact animal, and 3) that HGF/SF-induced liver enlargement is associated with changes in serum biochemistry.

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Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia

European Journal Of Haematology ◽

10.1111/j.1600-0609.1999.tb01733.x ◽

2009 ◽

Vol 62 (2) ◽

pp. 129-134 ◽

Cited By ~ 16

Author(s):

H. Hjorth-Hansen ◽

C. Seidel ◽

J. Lamvik ◽

M. Börset ◽

A. Sundan ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Elevated Serum ◽

Serum Concentrations ◽

Myelocytic Leukaemia ◽

Acute Myelocytic Leukaemia ◽

Hepatocyte Growth

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Hepatocyte Growth Factor Plays a Key Role in Insulin Resistance-Associated Compensatory Mechanisms

Endocrinology ◽

10.1210/en.2012-1496 ◽

2012 ◽

Vol 153 (12) ◽

pp. 5760-5769 ◽

Cited By ~ 42

Author(s):

Tiago G. Araújo ◽

Alexandre G. Oliveira ◽

Bruno M. Carvalho ◽

Dioze Guadagnini ◽

André O.P. Protzek ◽

...

Keyword(s):

Insulin Resistance ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Insulin Signaling ◽

Compensatory Mechanism ◽

Β Cell ◽

Compensatory Mechanisms ◽

Diet Induced Obesity ◽

Dose Dependent ◽

Hepatocyte Growth

Abstract Insulin resistance is present in obesity and in type 2 diabetes and is associated with islet cell hyperplasia and hyperinsulinemia, but the driving forces behind this compensatory mechanism are incompletely understood. Previous data have suggested the involvement of an unknown circulating insulin resistance-related β-cell growth factor. In this context, looking for candidates to be a circulating factor, we realized that hepatocyte growth factor (HGF) is a strong candidate as a link between insulin resistance and increased mass of islets/hyperinsulinemia. Our approach aimed to show a possible cause-effect relationship between increase in circulating HGF levels and compensatory islet hyperplasia/hyperinsulinemia by showing the strength of the association, whether or not is a dose-dependent response, the temporality, consistency, plausibility, and reversibility of the association. In this regard, our data showed: 1) a strong and consistent correlation between HGF and the compensatory mechanism in three animal models of insulin resistance; 2) HGF increases β-cell mass in a dose-dependent manner; 3) blocking HGF shuts down the compensatory mechanisms; and 4) an increase in HGF levels seems to precede the compensatory response associated with insulin resistance, indicating that these events occur in a sequential mode. Additionally, blockages of HGF receptor (Met) worsen the impaired insulin-induced insulin signaling in liver of diet-induced obesity rats. Overall, our data indicate that HGF is a growth factor playing a key role in islet mass increase and hyperinsulinemia in diet-induced obesity rats and suggest that the HGF-Met axis may have a role on insulin signaling in the liver.

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Hepatocyte growth factor alleviates hepatic insulin resistance and lipid accumulation in high-fat diet-fed mice

Journal of Diabetes Investigation ◽

10.1111/jdi.12904 ◽

2018 ◽

Vol 10 (2) ◽

pp. 251-260 ◽

Cited By ~ 6

Author(s):

Yali Jing ◽

Qingmin Sun ◽

Xiaolu Xiong ◽

Ran Meng ◽

Sunyinyan Tang ◽

...

Keyword(s):

Insulin Resistance ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Lipid Accumulation ◽

High Fat Diet ◽

Hepatic Insulin Resistance ◽

High Fat ◽

Hepatocyte Growth

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Elevated serum concentrations of activated hepatocyte growth factor activator in patients with multiple myeloma

European Journal Of Haematology ◽

10.1111/j.1600-0609.2008.01130.x ◽

2008 ◽

Cited By ~ 6

Author(s):

K. F. Wader ◽

U. M. Fagerli ◽

R. U. Holt ◽

B. Stordal ◽

M. Børset ◽

...

Keyword(s):

Multiple Myeloma ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Elevated Serum ◽

Serum Concentrations ◽

Hepatocyte Growth Factor Activator ◽

Hepatocyte Growth

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Ezetimibe ameliorates atherogenic lipids profiles, insulin resistance and hepatocyte growth factor in obese patients with hypercholesterolemia

Lipids in Health and Disease ◽

10.1186/1476-511x-14-1 ◽

2015 ◽

Vol 14 (1) ◽

Cited By ~ 22

Author(s):

Hisashi Adachi ◽

◽

Hitoshi Nakano ◽

Kiichiro Yamamoto ◽

Masashi Nakata ◽

...

Keyword(s):

Insulin Resistance ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Obese Patients ◽

Hepatocyte Growth

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Elevated Serum Concentrations of Hepatocyte Growth Factor in Patients With Multiple Myeloma

Blood ◽

10.1182/blood.v91.3.806 ◽

1998 ◽

Vol 91 (3) ◽

pp. 806-812 ◽

Cited By ~ 148

Author(s):

Carina Seidel ◽

Magne Børset ◽

Ingemar Turesson ◽

Niels Abildgaard ◽

Anders Sundan ◽

...

Keyword(s):

Regression Analysis ◽

Growth Factor ◽

Prognostic Factor ◽

Hepatocyte Growth Factor ◽

Cox Regression ◽

Elevated Serum ◽

Cox Regression Analysis ◽

Β2 Microglobulin ◽

Serial Samples ◽

Hepatocyte Growth

Abstract Serum from 398 myeloma patients at diagnosis and serial samples from 29 patients were analysed for hepatocyte growth factor (HGF). HGF was elevated at diagnosis in 43% of myeloma patients compared with healthy controls (median 1.00 ng/mL and 0.44 ng/mL, respectively;P < .00001). In the group with elevated HGF levels 46% of the patients reached plateau phase, as compared with 60% of the patients with low HGF levels (P = .005), and the median survival time was 21 and 32 months, respectively (P = .002). In a univariate Cox regression analysis, HGF was a significant predictor of mortality (P = .02). In the subgroup of patients with β2-microglobulin levels less than or equal to 6 mg/L, high versus low HGF was a prognostic factor when a multivariate Cox regression analysis was performed. In serial samples HGF was higher at the time of diagnosis and relapse (median 0.57 ng/mL and 0.52 ng/mL, respectively; P = .0018) than at response (median 0.24 ng/mL, P = .008). We conclude that HGF may be a useful follow-up parameter in myeloma patients. Measurement of HGF may identify a group of patients with poor response to melphalan-prednisone treatment and short survival. HGF was a prognostic factor in patients with high levels of β2-microglobulin.

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Elevated serum level of hepatocyte growth factor predicts development of new syndesmophytes in men with ankylosing spondylitis

Rheumatology ◽

10.1093/rheumatology/keaa460 ◽

2020 ◽

Author(s):

Anna Deminger ◽

Eva Klingberg ◽

Merja Nurkkala ◽

Mats Geijer ◽

Hans Carlsten ◽

...

Keyword(s):

Cohort Study ◽

Ankylosing Spondylitis ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Radiographic Progression ◽

Elevated Serum ◽

Regression Analyses ◽

Baseline Serum ◽

Hepatocyte Growth

Abstract Objectives To study baseline serum hepatocyte growth factor (s-HGF) as a predictor of spinal radiographic progression overall and by sex and to analyse factors correlated to changes in s-HGF in patients with AS. Methods At baseline and the 5-year follow-up, s-HGF was analysed with ELISA. Spinal radiographs were graded according to modified Stoke Ankylosing Spondylitis Spinal Score. Radiographic progression was defined as ≥2 modified Stoke Ankylosing Spondylitis Spinal Score units/5 years or development of ≥1 syndesmophyte. Logistic regression analyses were used. Results Of 204 baseline participants, 163 (80%) completed all examinations at the 5-year follow-up (54% men). Baseline s-HGF was significantly higher in men who developed ≥1 syndesmophyte compared with non-progressors, median (interquartile range) baseline s-HGF 1551 (1449–1898) vs 1436 (1200–1569) pg/ml, P = 0.003. The calculated optimal cut-off point for baseline s-HGF ≥1520 pg/ml showed a sensitivity of 70%, a specificity of 69% and univariate odds radio (95% CI) of 5.25 (1.69, 14.10) as predictor of development of ≥1 new syndesmophyte in men. Baseline s-HGF ≥1520 pg/ml remained significantly associated with development of ≥1 new syndesmophyte in men in an analysis adjusted for the baseline variables age, smoking, presence of syndesmophytes and CRP, odds radio 3.97 (1.36, 11.60). In women, no association with HGF and radiographic progression was found. Changes in s-HGF were positively correlated with changes in ESR and CRP. Conclusion In this prospective cohort study elevated s-HGF was shown to be associated with development of new syndesmophytes in men with AS.

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