Abstract
Hypoglycemia-associated autonomic failure (HAAF) is a serious complication of diabetes which is associated with the absence of physiological homeostatic counter-regulatory mechanisms that are controlled by the hypothalamus and sympathetic nervous system. Identification of biomarkers for early detection of HAAF requires an advanced understanding of molecular signature of hypoglycemia which is yet to be identified. The outcomes of the present study have shown that the viability and the apoptotic rate of the hypothalamic neurons (mHypoE-N39) were decreased significantly due to hypoglycemia in a dose-dependent fashion (p < 0.05). Although there are more than 1000 miRNAs differentially expressed in hypothalamus, only twelve miRNAs (miR-7a, miR-7b, miR-9, miR-29b, miR-29c, miR-30a, miR-30b, miR-30c, miR-101b-3p, miR-181a-5p, miR-378-3p and miR-873-5p) were correlated to two main hypothalamic regulatory proteins, FOS and FTO. Expression of these proteins was very sensitive to hypoglycemia. We demonstrated that hypoglycemia modulates the expression of hypothalamic miRNAs that are related to FOS and FTO.
Highlights
Hypothalamus is composed of multiple clusters of neurons which express different hormones, neurotransmitters and proteins
The metabolic processes in the brain are mainly dependent on the peripheral glucose and any reduction in glucose beyond the physiological levels leads to activation of robust counter-regulatory response (CRR) [7]
Effects of low glucose conditions on the viability of hypothalamic neurons The first group of experiments was designed to examine the viability of the hypothalamic neurons in response to different conditions of low glucose concentrations
Summary
Hypothalamus is composed of multiple clusters of neurons which express different hormones, neurotransmitters and proteins The latter are involved in regulation of a wide range of homeostatic processes, including cognitive functions, glucose sensing and metabolism [1, 2]. The metabolic processes in the brain are mainly dependent on the peripheral glucose and any reduction in glucose beyond the physiological levels leads to activation of robust counter-regulatory response (CRR) [7]. The latter involves a group of neurons within the hypothalamus and the rostral ventro-lateral medulla which activate the sympathetic system that, in turn, stimulates adreno-medullary response leading to hypoglycemia awareness [8, 9]. Given that in diabetes mellitus (DM) the responses of the pancreatic islets to hypoglycemia are disabled, the body mainly depends on autonomic-adreno-medullary regulatory system to correct the hypoglycemia [11]
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