In This Issue of Diabetes

摘要

A preclinical study by lyer et al. (p. 3453) investigating renal denervation in obese dogs suggests that the procedure can totally reverse high-fat diet-induced hepatic insulin resistance and that it does so by primarily decreasing hepatic-specific gluconeogenic gene expression. The study used a nonhypertensive obese canine model to assess insulin sensitivity before and after 6 weeks of high-fat diet and then again after a surgical renal denervation procedure or a sham operation. The 6-week high-fat diet induced insulin resistance in both groups, and in the sham group, insulin resistance continued despite the operation. In the renal denervation group, however, hepatic insulin sensitivity was completely restored following the operation. According to the authors, they felt it was reasonable to assume that the insulin suppression of normal glucose production was due to the suppression of gluconeogenesis and, on that basis, went on to assess whether gene expression associated with that process was also suppressed. Accordingly, they report that the procedure did result in the suppression of certain hepatic gluconeogenic genes, with a concurrent upregulation of the liver X receptor a. In short, they say that the procedure restored the impaired ability of insulin to suppress hepatic glucose production-an outcome that will likely have ramifications for diabetes treatment directly. Previously, renal denervation has mainly been viewed as a potential intervention for hypertension. One further observation that they say may be important is that the dogs that received the renal denervation operation were also resistant to hypoglycemia, suggesting yet another potential application in diabetes. They conclude that "the translational potential of this work to the clinical setting will be fascinating to investigate." Commenting more widely, author Malini S. Iyer told Diabetes: "Elevated fasting glucose is a biomarker of diabetes. Our results suggest that the kidneys play a role in controlling liver glucose output via the sympathetic nervous system. Exploring this mechanism can lead to new therapeutic targets in the treatment of prediabetes."