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    • STA-4783 The previous studies focused on the

    2022-05-18

    The previous studies focused on the regulation of GK activity by nutrients directly or nutritional hormones (Panserat et al., 2014), there was still a lack of studies paid attention to GK both in activity level and transcriptional level. Besides, the GK regulation by dietary STA-4783 has been definitely proved by different studies in some fish species (Caseras et al., 2000, Enes et al., 2008a, Enes et al., 2009, Pérez-Jiménez et al., 2007, Panserat et al., 2000, Polakof et al., 2011, Skiba-Cassy et al., 2013). This study investigated the modulation role of GK in carbohydrate metabolism from both enzymatic and molecular levels in liver synthetically. The hepatic GK activity and GK mRNA abundance increased (P<0.05) when the experimental diets were supplemented with increasing carbohydrate level in our study. The result in the present study was consistent with the previous researches in mammals (Ferre et al., 1996). Similar researches were also reported in aquatic animals such as rainbow trout (Oncorhynchus mykiss) (Panserat et al., 2000, Polakof et al., 2007, Polakof et al., 2011, Skiba-Cassy et al., 2013, Soengas et al., 2006), European sea bass (Dicentrarchus labrax) (Pérez-Jiménez et al., 2007), gilthead sea bream (Sparus aurata) (Caseras et al., 2000, Enes et al., 2008a). In rainbow trout, the level of enzymic activities is equivalent to that found in mammals (Panserat et al., 2000, Polakof et al., 2007, Soengas et al., 2006). However, the induction of GK activity by carbohydrates is lower in omnivorous fish known to utilize carbohydrates well, i.e. common carp (Capilla et al., 2004), Indian carp (Catla catla) (Kumar et al., 2009), silver sea bream (Pagrus auratus) (Leung and Woo, 2012), zebrafish (Danio rerio) (Robison et al., 2008) and tilapia (Oreochromis niloticus×O. aureus) (Shiau, 1997). This suggests that induction of hepatic GK is not a limited factor to utilization of dietary carbohydrates. In addition, the sources of carbohydrates also could affect the GK regulation. The previous studies on European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) showed that the hepatic GK activities were higher in fish fed glucose and the maltose diets than those fed with dextrin and starch (Enes et al., 2008b, Enes et al., 2010). Moreover, this induction of GK activity is mainly linked to the induction of To-GK gene expression in the liver (Panserat et al., 2014). In the present study, the dietary carbohydrate level affected hepatic GK activity, and higher level of dietary carbohydrates was accompanied with higher To-GK gene expression. Similarly, the previous studies demonstrated that the increased GK gene expression in the liver of carnivorous fish appears after long-term feeding with carbohydrates but also after a single meal with carbohydrates, as shown in rainbow trout (Panserat et al., 2001, Seiliez et al., 2011, Skiba-Cassy et al., 2013). This suggested that the To-GK gene expression in fish can be regulated by nutritional factor through nutrient (carbohydrate) directly. Overall, the trends of the hepatic GK activity and expression are similar in this study, however, there was inconsistent between the hepatic GK activity and relative expression in the M-CHO group. Our results indicate a delayed stimulatory effect on the GK activity in fish liver which was similar to the previous study on Topmouth culter (Erythroculter ilishaeformis) (Liu et al., 2008). These results suggest that the delayed stimulation of GK activity observed in fish may result from the relative inability of fish to utilize dietary carbohydrates. However, this needs to be explored further.
    Introduction Diabetes is one of the most common chronic diseases worldwide. According to the International Diabetes Federation, diabetes affected approximately 425 million people in 2017, and this number is expected to rise to 629 million by 2045. The increasing prevalence of diabetes is driven by a variety of factors, including diet, urbanization, and obesity. Type 2 diabetes mellitus (T2DM) is the predominant form of the disease and constitutes the majority of adult cases worldwide [1,2]. T2DM is typically characterized by hyperglycemia, insulin resistance, abnormally elevated hepatic glucose production, and inadequate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells [3]. Insufficient blood glucose control increases the risk of vascular complications such as coronary artery disease, peripheral arterial disease, stroke, nephropathy, neuropathy, and retinopathy [4]. Although various oral anti-hyperglycemic agents are available, monotherapy or combination regimens are frequently inadequate for maintaining blood glucose levels in the long term. Furthermore, many of these agents exhibit side effects such as hypoglycemia, weight gain, gastrointestinal side effects, and genitourinary infection [5,6]. Therefore, an unmet need exists for more effective therapies offering improved efficacy and safety for the management of diabetes.