Sarcopoterium spinosum extract improved insulin sensitivity in mice models of glucose intolerance and diabetes

BACKGROUND: The glucose lowering properties of Sarcopoterium spinosum, a traditional medicinal plant, were previously validated by us using KK-Ay mice as a genetic model for type 2 diabetes (T2D). OBJECTIVE: To clarify the effects of Sarcopoterium spinosum extract (SSE) on diet-induced glucose intolerance and to investigate SSE effects on carbohydrate and lipid metabolism in target tissues of both high-fat-diet (HFD)-fed and KK-Ay mice. RESULTS: Mice were given SSE (70 mg/day) for 6 weeks. SSE improved glucose tolerance and insulin sensitivity in HFD-fed mice as was demonstrated previously in KK-Ay mice. Higher insulin sensitivity was validated by lower serum insulin and activation of the insulin signaling cascade in skeletal muscle and liver of SSE-treated mice in both models. H&E staining of the livers demonstrated lower severity of steatosis in SSE-treated mice. Several model-specific effects of SSE were observed–mRNA expression of proinflammatory genes and CD36 was reduced in SSE-treated KK-Ay mice. Hepatic mRNA expression of PEPCK was also reduced in SSE-treated KK-Ay mice, while other genes involved in carbohydrates and lipid metabolism were not affected. HFD-fed mice treated by SSE had elevated hepatic glycogen stores. Gluconeogenic gene expression was not affected, while GCK expression was increased. HFD-induced hepatic steatosis was not affected by SSE. However, while genes involved in lipid metabolism were downregulated by HFD, this was not found in HFD-fed mice given SSE, demonstrating an expression profile which is similar to that of standard diet-fed mice. CONCLUSION: Our study supports the insulin sensitizing activity of SSE and suggests that this extract might improve other manifestations of the metabolic syndrome.