Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis

Abstract

IntroductionThe habenular nucleus (Hb), a famous relay station in the midbrain, is vital for controlling many physiological functions of vertebrates. The role of Hb in the pathogenesis of depression has been thoroughly studied, but whether it functions in the pathogenesis of diabetes remains unknown. In this study, we found that Hb lesions could improve glucose metabolism in type 2 diabetes mellitus (T2DM) by inhibiting the peripheral sympathetic nervous system and hepatic glucose production.Research design and methodsT2DM rats were induced by a high-carbohydrate and fat diet combined with streptozotocin. Electrical lesion method was applied to suppress the function of Hb. Serum and tissue samples of rats in the control group, T2DM group, sham group, and Hb lesion group were detected by ELISA, western blotting, and biochemical methods.ResultsCompared with the sham group, the expression levels of AMPK phosphorylation and insulin receptor (IR) were significantly increased, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxylated kinase were reduced in the liver of the Hb lesion group. In the glucose tolerance test and pyruvate tolerance test, the lesion group showed stronger glucose tolerance and lower hepatic gluconeogenesis than the sham. These results suggest that Hb lesions not only effectively increase insulin sensitivity and improve insulin resistance but also inhibit gluconeogenesis in T2DM rats. Moreover, Hb lesions increase the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, glucocorticoid receptor, and IR in the hippocampus. In this study, we also found that Hb lesions increase the content of acetylcholine in the adrenal glands and reduce the content of epinephrine in both the adrenal glands and the liver, which may be the main reason for the Hb lesions to regulate glucose metabolism in the liver.ConclusionHb is an important neuroanatomical target for the regulation of glucose metabolism in the central nervous system of diabetic rats.

Spectro-spatial features in distributed human intracranial activity proactively encode peripheral metabolic activity

“…Thus, the HFA at any given point represents an average of one-minute recording. Similarly, the analytic signals of delta (1-4 Hz), theta (4-8 Hz), alpha (8)(9)(10)(11)(12), beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), and gamma bands (25-70 Hz) were obtained using the same approach, except 4th order Butterworth filter was used as the bandpass filter. Interictal epileptiform discharges (IEDs) were computed using an automated algorithm as previously described 53 .…”

“…The amygdalohippocampal complex (AHC) has also been shown to harbor these neurons [8][9][10] and recently, the rodent hippocampus was reported to exert a modulatory effect on peripheral glucose level changes through sharp wave-ripples (SPW-Rs) 9 . Further, the habenular nucleus has been implicated in regulation of glucose metabolism, as lesion in this area increased insulin sensitivity 11 . Other direct glucose-sensing neurons have also been found in the nucleus accumbens 12 , the thalamus 13 , and the prefrontal cortex 14 .…”