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Hepatocyte growth factor as a potential index of complication in diabetes mellitus
S Nakamura1, R Morishita, A Moriguchi
1Department of Geriatric Medicine, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Insights
Hepatocyte growth factor (HGF) levels are decreased in diabetes, contributing to endothelial dysfunction. However, HGF levels increase with hypertension severity in diabetic patients, suggesting HGF may indicate diabetic complications.
Area of Science:
- Endocrinology and Metabolism
- Vascular Biology
- Molecular Medicine
Background:
- Diabetes mellitus (DM) is associated with endothelial dysfunction and increased risk of microvascular and macrovascular complications.
- The precise mechanisms underlying endothelial dysfunction in diabetes remain unclear.
- Hepatocyte growth factor (HGF), crucial for vascular health, is downregulated by high glucose, potentially exacerbating diabetic endothelial dysfunction.
Purpose of the Study:
- To investigate the role of HGF in diabetes by measuring serum HGF levels.
- To explore the correlation between HGF levels and glycemic control (HbA1c) in diabetic patients.
- To examine the relationship between HGF levels and hypertension in diabetic individuals.
Main Methods:
- HGF levels were measured in the KKAy mouse model of non-insulin-dependent diabetes mellitus (NIDDM) and control mice.
- Serum HGF concentrations were assessed in NIDDM patients, categorized by normotensive status and varying degrees of hypertension.
- Hemoglobin A1c (HbA1c) levels were correlated with serum HGF concentrations.
Main Results:
- Serum and tissue HGF concentrations were significantly lower in diabetic KKAy mice compared to controls.
- A significant negative correlation was observed between serum HGF and HbA1c levels in diabetic patients without complications.
- Serum HGF levels were significantly lower in diabetic patients without hypertension but significantly higher in those with hypertension, increasing with complication severity.
Conclusions:
- Decreased local HGF may contribute to endothelial dysfunction in diabetes.
- Serum HGF levels correlate negatively with glycemic control in uncomplicated diabetes.
- Elevated serum HGF levels in diabetic patients correlate with the presence and severity of hypertension, suggesting HGF as a potential biomarker for diabetic complications.
Objective:
Diabetes mellitus (DM), characterized by the premature development of microvascular and macrovascular disease, shows a loss of vasodilatory properties of resistance vessels. However, the mechanisms of endothelial dysfunction in diabetes have not yet been clarified. Hepatocyte growth factor (HGF) in vascular cells was down-regulated by high glucose levels, potentially accelerating the endothelial dysfunction in DM. In this study, the serum HGF level was measured to investigate further the role of HGF in DM.
Methods:
Tissue and circulating HGF levels were measured in the KKAy mouse, a rodent model of non-insulin-dependent diabetes mellitus (NIDDM), and lean C57 BL control mice. Then, serum HGF concentrations were measured in NIDDM patients without liver, kidney or lung damage. For the study of serum HGF concentration, 30 normotensive and age-matched 58 DM patients were studied. The 58 DM patients were divided into 26 patients without hypertension and 32 patients with hypertension [22 patients without hypertensive complications (WHO I) and 10 patients with hypertensive complications (WHO II + III)].
Results:
The serum HGF concentration in KKAy mice was significantly lower than that in control mice (P < 0.01), at 14 weeks of age when they exhibit features of diabetes. Similarly, tissue HGF concentrations in the heart and kidney were decreased significantly in KKAy mice compared with control C57 BL mice (P< 0.05). The serum HGF concentration showed a significant negative correlation with hemoglobin (Hb) A(Ic) concentration (P< 0.01, r= -0.41). Since the serum HGF concentration is a potential index of the severity of hypertension, the serum levels of HGF in DM patients without and with hypertension were examined. The serum HGF concentration in DM patients without hypertension was significantly lower than that in normal subjects (P< 0.05), whereas that in DM patients with hypertension was significantly higher than that in normal subjects (P < 0.01). Moreover, the serum HGF concentration in DM patients with hypertensive complications was further higher than that in others (P < 0.01).
Conclusion:
The present data showed that serum, cardiac and renal HGF concentrations in KKAy mice were significantly decreased compared with control mice. Therefore, a decrease in local HGF may be a trigger of endothelial dysfunction in DM. Clinical data also demonstrated a significant negative correlation between serum HGF and HbA(Ic) concentrations in diabetic patients without complications. In contrast, the serum concentration of HGF was significantly elevated depending on the severity of hypertension. These results suggest that HGF may be a new index of complications such as hypertension in DM.