Abstract
BackgroundType 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. Liver injury is one of these that severely affects patients with diabetes. Fibroblast growth factor 1 (FGF1) has glucose-lowering activity and plays a role in modulation of several liver injuries. Nevertheless, the effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown.MethodsTo further investigate the effect of FGF1 on diabetic liver injury, we divided db/db mice into two groups and intraperitoneally (i.p.) injected either with FGF1 at 0.5 mg/kg body weight or saline every other day for 4 weeks. Then body weights were measured. Serum and liver tissues were collected for biochemical and molecular analyses.ResultsFGF1 significantly reduced blood glucose and ameliorated diabetes-induced liver steatosis, fibrosis, and apoptosis. FGF1 also restored defective hepatic autophagy in db/db mice. Mechanistic investigations showed that diabetes markedly induced oxidative stress and endoplasmic reticulum stress and that FGF1 treatment significantly attenuated these effects.ConclusionsFGF1-associated glucose level reduction and amelioration of cellular stress are potential protective effects of FGF1 against diabetes-induced liver injury.
Highlights
Type 2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance and pancreatic cell failure (Kasuga, 2006)
A previous study showed that a single injection of Fibroblast growth factor 1 (FGF1) was sufficient to restore blood glucose levels to the normal range for more than 2 days in both db/db and diet-induced obesity (DIO) mouse models (JaeMyoung et al, 2014)
In agreement with that study, our results showed that FGF1 treatment markedly reduced blood glucose levels in db/db mice (Figure 1B)
Summary
Type 2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance and pancreatic cell failure (Kasuga, 2006). Hyperglycemia resulting in glucotoxicity is the primary pathophysiological trigger of diabetes-induced complications (Wu et al, 2015a; Wu et al, 2016). Liver injury occurs commonly in patients with diabetes (Gezginci-Oktayoglu et al, 2009). FGF1-Associated Glucose Level Reduction and Amelioration damage caused by diabetes is characterized by abnormal liver enzyme levels, steatosis, fibrosis, and cirrhosis. There are many mechanisms mediating liver damage caused by diabetes, including hyperglycemia, oxidative stress, endoplasmic reticulum stress, and advanced glycation end-products (JaeMyoung et al, 2014). It is important to detail these pathophysiological mechanisms and to explore effective therapeutic strategies to meliorate diabetes-induced liver injury. Type 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. The effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown
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