Mice with nucleus tractus solitarius injury induced by chronic restraint stress present impaired ability to raise blood glucose and glucagon levels when blood glucose levels plummet.

Abstract

Chronic restraint stress (CRS) induces insulin-resistant hyperglycemia by inducing injury to the brain neurons in the nucleus tractus solitarius (NTS). However, the CRS mice did not suffer from hypoglycemia. In this study, mice of both CRS and NTS mechanical injury models were induced to investigate whether impaired glucose metabolism has changed upon the extension of the survival time after modeling. Body weight, food and water intake, fasting blood glucose, glucose tolerance, and glucose metabolism related to blood hormone levels were monitored for 12 weeks following the induction of injury. The mice were also administered with insulin intraperitoneally, and the blood glucose and glucagon levels were measured and compared to those in the control mice administered with saline. The results showed that the body weights of CRS-hyperglycemic mice were significantly higher than those in the control group, while the body weights of NTS mechanically injured mice were significantly lower than those in the control group. The food and water intake of both CRS-hyperglycemic and NTS mechanically injured mice were significantly more than those in the control groups. Although the levels of fasting blood glucose and resting serum hormone in the injured mice have returned to normal levels, the utilization of glucose and hypoglycemic counterregulation (the response that raises the blood glucose levels) was impaired in either CRS-hyperglycemic or NTS mechanically injured mice. The blood glucagon levels following insulin administration showed abnormal increase. These findings suggest that the CRS-induced NTS injury resulted not only in early insulin-resistant hyperglycemia but also impaired the ability to raise blood glucose and glucagon levels when blood glucose levels plummet in the later stage.