Glucose Metabolism Disorder Induces Spermatogenic Dysfunction in Northern Pig-Tailed Macaques (Macaca leonina) With Long-Term SIVmac239 Infection

Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV− and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet β cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet β cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.

Effect of Zanthoxylum alkylamides on glucose metabolism in streptozotocin-induced diabetic Sprague–Dawley rats

This research aimed at investigating the hypoglycemic effect of Zanthoxylum alkylamides and whether TRPV1 receptor could participate in the glucose metabolism by using streptozotocin-induced diabetic rat model. The results showed that the blood glucose measured in the Zanthoxylum alkylamides treated group (ALK) showed significantly lower values than that in the model group (Model). Significant improvements in the oral glucose tolerance as well as plasma insulin and hepatic glycogen were also observed in the ALK group, when compared to the model group. However, the improving effects of Zanthoxylum alkylamides on glucose metabolism disorder in diabetic rats were markedly inhibited by capsazepine as the TRPV1 receptor antagonist. In addition, there were significant differences in the levels of mRNA and protein of phosphoenolpyruvate carboxylase (PEPCK), gucose-6-phosphatase (G6Pase), glucokinase (GK) and cannabinoid receptor l (CB1) in the livers of the ALK group compared to model group. Meanwhile, ALK group also exhibited a remarkable increase in the pancreatic-duodenal homeobox 1 (PDX-1), glucose transporter 2 (GLUT 2), GK levels and a significant decrease in the expression levels of CB1 in the pancreas, while the presence of capsazepine would affected the expression of these genes. These findings indicate that Zanthoxylum alkylamides could ameliorate the glucose metabolism disorder in diabetic rats. Furthermore, the TRPV1 receptor could participate in regulating the expressions of genes and proteins related to glucose metabolism and insulin secretion in the liver and pancreas, and takes a role in the hypoglycemic process of Zanthoxylum alkylamides.