Abstract

BackgroundThe 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).ObjectiveTo 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.ResultsMice 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.ConclusionOur study supports the insulin sensitizing activity of SSE and suggests that this extract might improve other manifestations of the metabolic syndrome.

Highlights

  • Diabetes mellitus (DM) has reached epidemic proportions, affecting more than 170 million individuals worldwide and the number of affected subjects is expected to further increase in the coming years [1]

  • Higher insulin sensitivity was validated by lower serum insulin and activation of the insulin signaling cascade in skeletal muscle and liver of spinosum extract (SSE)-treated mice in both models

  • hematoxylin and eosin (H&E) staining of the livers demonstrated lower severity of steatosis in SSE-treated mice

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Summary

Introduction

Diabetes mellitus (DM) has reached epidemic proportions, affecting more than 170 million individuals worldwide and the number of affected subjects is expected to further increase in the coming years [1]. Several drugs, acting via various mechanisms, are approved for treatment of diabetes. Despite the availability of these medications acting on different targets, around 50% of patients failed to maintain glycemic control according to the treatment’s goals as recommended by international diabetic associations [4,5]. These data further illustrate the continual need for additional research and development of alternative drugs with novel mechanisms to slow disease progression and its related complications. 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)

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