Transcriptomic Responses of Skeletal Muscle to Acute Exercise in Diabetic Goto-Kakizaki Rats

Abstract

Physical activity exerts positive effects on glycemic control in type 2 diabetes (T2D), which is mediated in part by extensive metabolic and molecular remodeling of skeletal muscle in response to exercise, while many regulators of skeletal muscle remain unclear. In the present study, we investigated the effects of acute exercise on skeletal muscle transcriptomic responses in the Goto-Kakizaki (GK) rats which can spontaneously develop T2D. The transcriptomes of skeletal muscle from both 8-week-old GK and Wistar rats that underwent a single exercise session (60 min running using an animal treadmill at 15 m/min) or remained sedentary were analyzed by next-generation RNA sequencing. We identified 819 differentially expressed genes in the sedentary GK rats compared with those of the sedentary Wistar rats. After a single bout of running, we found 291 and 598 genes that were differentially expressed in the exercise GK and exercise Wistar rats when compared with the corresponding sedentary rats. By integrating our data and previous studies including RNA or protein expression patterns and transgenic experiments, the downregulated expression of Fasn and upregulated expression of Tbc1d1 , Hk2 , Lpin1 , Ppargc1a , Sorbs1 , and Hmox1 might enhance glucose uptake or improve insulin sensitivity to ameliorate hyperglycemia in the exercise GK rats. Our results provide mechanistic insight into the beneficial effects of exercise on hyperglycemia and insulin action in skeletal muscle of diabetic GK rats.

Effects of Voluntary Running Exercise on Skeletal Muscle Properties in Nonobese Rats with Type 2 Diabetes

“…Some previous studies (Macia et al 2018, Morifuji et al 2012, Qi et al 2011 observed that running training did not reduce the increased blood glucose levels in diabetic GK rats. In contrast, other studies (Fu et al 2019, Kim et al 2011 showed that the high blood glucose levels in diabetic GK rats were decreased by running training. However, all these aforementioned studies (Fu et al 2019, Kim et al 2011, Macia et al 2018, Morifuji et al 2012, Qi et al 2011 used forced running training on a treadmill at a constant speed and time, and therefore, did not consider the effects of different running speeds and times.…”

“…In contrast, other studies (Fu et al 2019, Kim et al 2011 showed that the high blood glucose levels in diabetic GK rats were decreased by running training. However, all these aforementioned studies (Fu et al 2019, Kim et al 2011, Macia et al 2018, Morifuji et al 2012, Qi et al 2011 used forced running training on a treadmill at a constant speed and time, and therefore, did not consider the effects of different running speeds and times. In this study, the growth-related increase in the fasting blood glucose levels of diabetic GK rats was inhibited by voluntary running exercise (Fig.…”

“…Therefore, an exercise-induced increase in Pgc-1α mRNA levels in skeletal muscles is expected to lead to a fiber type shift and improve muscle SDH activity. Previous studies (Fu et al 2019, Kim et al 2011, Macia et al 2018, Morifuji et al 2012, Qi et al 2011 examined the effects of running exercise on diabetes; however, these studies used forced running training on a treadmill, and the amount of exercise was constant for all exercised rats. Furthermore, treadmill exercise is stressful because the rats are forcibly run at a constant speed.…”

No evidence for change in expression of TBC1D1 and TBC1D4 genes in cultured human adipocytes stimulated by myokines and adipokines

“…Diabetes was shown to down-regulate the expression of TBC1D4 in skeletal muscle and adipose tissue of humans and rodents [ 11 , 12 , 13 , 14 ]. Tbc1d1 was shown to be up-regulated in diabetic rat muscle [ 15 ]. One study showed no significant change in both TBC1D1 and TBC1D4 protein abundance in diabetic patients [ 16 ].…”

Transcriptomic responses of hypothalamus to acute exercise in type 2 diabetic Goto-Kakizaki rats

“…It has been observed that only a single session of exercise can attenuate hyperglycemia and enhance insulin sensitivity (Colberg et al, 2010). Over the decades, many studies on exercise have focused on peripheral tissues to explore the adaptive mechanisms in the T2D (Sylow et al, 2017; Hussey et al, 2011; Fu et al, 2019). Interestingly, recent research suggested that exercise training of obese mice could improve high-fat diet impaired proopiomelanocortin (POMC)-expressing neurons, protect against inflammation and aid in maintaining energy balance in the hypothalamus (Ropelle et al, 2010; Laing et al, 2016).…”