Abstract
Oxidative stress (OS) plays a role in hyperglycemia induced islet β cell dysfunction, however, studies on classic anti-oxidants didn’t show positive results in treating diabetes. We previously demonstrated that the prescribed Chinese herbal medicine preparation “Qing Huo Yi Hao” (QHYH) improved endothelial function in type 2 diabetic patients. QHYH protected endothelial cells from high glucose-induced damages by scavenging superoxide anion and reducing production of reactive oxygen species. Its active component protected C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction. In the present study, we investigated whether QHYH protected islet β cell function exacerbated by high fat diet (HFD) in hyperglycemic GK rats. 4-week-old male rats were randomly divided into high HFD feeding group (n = 20) and chow diet feeding group (n = 10). Each gram of HFD contained 4.8 kcal of energy, 52% of which from fat. Rats on HFD were further divided into 2 groups given either QHYH (3 ml/Kg/d) or saline through gastric tube. After intervention, serum glucose concentrations were monitored; IPGTTs were performed without anesthesia on 5 fasting rats randomly chosen from each group on week 4 and 16. Serum malondialdehyde (MDA) concentrations and activities of serum antioxidant enzymes were measured on week 4 and 16. Islet β cell mass and OS marker staining was done by immunohistochemistry on week 16. QHYH prevented the exacerbation of hyperglycemia in HFD feeding GK rats for 12 weeks. On week 16, it improved the exacerbated glucose tolerance and prevented the further loss of islet β cell mass induced by HFD. QHYH markedly decreased serum MDA concentration, increased serum catalase (CAT) and SOD activities on week 4. However, no differences of serum glucose concentration or OS were observed on week 16. We concluded that QHYH decreased hyperglycemia exacerbated by HFD in GK rats by improving β cell function partly via its antioxidant effect.
Highlights
Progressive islet b cell dysfunction is one of the two fundamental pathogenic features of type 2 Diabetes Mellitus (T2D)
With the prolongation of high fat diet, hyperglycemia was exacerbated which caused more infection, and injuries caused by frequent blood taken, led to more death of the rats
The main findings of the present study were that the prescribed traditional Chinese medicine preparation QHYH partly reversed islet b cell dysfunction exacerbated by high fat diet in hyperglycemic GK rats that it prevented the elevation of blood glucose concentrations induced by high fat diet for 12 weeks, improved the exacerbated glucose tolerance and prevented the further loss of islet b cell mass induced by high fat diet after 16 weeks of intervention
Summary
Progressive islet b cell dysfunction is one of the two fundamental pathogenic features of type 2 Diabetes Mellitus (T2D). Islet b cell dysfunction is considered to be essential for the development of T2D, since its insufficient compensation leads to the onset of glucose intolerance [1] and its progressive exacerbation explains the unmet needs of long-term glycemic control [2,3]. Accumulating evidence confirmed that islet b cell dysfunction, manifested by secretory incapability and reduced b cell mass, is associated with increased oxidative stress (OS) induced by over-nutrition, hyperglycemia, dyslipidemia and chronic inflammation [4,5,6,7]. It has been confirmed that total antioxidant status in diabetic patients is markedly low [8,9], and the intrinsic anti-oxidative defence system of islet b cell is fragile [10]. Since clinical researches on classic anti-oxidants did not show promising results [8,11,12,13], it is suggested by Ceriello et al [14] that new antioxidant, either regulates free radical over-production at the mitochondrial level or increases intracellular anti-oxidant defence system, might be the key to link the theoretical possibility of antioxidant therapy to its practical use
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