Leptin is a key regulator of glucose metabolism in mammals, but the mechanisms of its action have remained elusive. We now show that signaling by extracellular signal-regulated kinase (ERK) and its upstream kinase MEK in the ventromedial hypothalamus (VMH) mediates the leptin-induced increase in glucose utilization as well as its insulin sensitivity in the whole body and in red-type skeletal mu...

Gilland, Kaitlyn Elizabeth. M.S., Purdue University, May 2016. Short-Term Effects of a Western Diet on the Number of Brain-Derived Neurotrophic Factor Immunoreactive Neurons in the Hypothalamic Arcuate, Ventromedial and Paraventricular Nuclei. Major Professor: Edward Fox. Brain-derived neurotrophic factor (BDNF) is an important anorexogenic factor and has been shown to be involved in obesity. I...

The mechanisms by which glucose regulates the activity of glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH) are largely unknown. We have previously shown that AMP-activated protein kinase (AMPK) increases nitric oxide (NO) production in VMH GI neurons. We hypothesized that AMPK-mediated NO signaling is required for depolarization of VMH GI neurons in response to decreased gl...

Glucose-sensing neurons in the ventromedial hypothalamus (VMH) are involved in the regulation of glucose homeostasis. Glucose-sensing neurons alter their action potential frequency in response to physiological changes in extracellular glucose, insulin, and leptin. Glucose-excited neurons decrease, whereas glucose-inhibited (GI) neurons increase, their action potential frequency when extracellul...

Phosphatidyl inositol 3-kinase (PI3K) signaling in the hypothalamus has been implicated in the regulation of energy homeostasis, but the critical brain sites where this intracellular signal integrates various metabolic cues to regulate food intake and energy expenditure are unknown. Here, we show that mice with reduced PI3K activity in the ventromedial hypothalamic nucleus (VMH) are more sensit...

The spontaneous activity of hypothalamic units was studied in chronic awake and ketamine-anesthetized rats. Ketamine appeared to decrease significantly the spontaneous firing of neurons in the ventromedial hypothalamic nucleus (VMH) but did not influence the activity in either the dorsomedial hypothalamic nucleus (DMH) or the lateral hypothalamic area (LHA). The responses obtained in the medial...

GABA(A) receptor-mediated responses manifest as either hyperpolarization or depolarization according to the intracellular Cl(-) concentration ([Cl(-)](i)). Here, we report a novel functional interaction between the Na-K-Cl cotransporter (NKCC) and GABA(A) receptor actions on glutamatergic presynaptic nerve terminals projecting to ventromedial hypothalamic (VMH) neurons. The activation of presyn...

A very low dose of leptin (50 ng) was microinjected into the ventro-medial hypothalamus (VMH) of each rat daily once for three days. Food intake and body weight were measured after leptin injections. Microinjection of leptin into the VMH reduced food intake by 33.3 % significantly (P<0.01) during three days of leptin injection compared to the control. Body weight was measured after 24 h, 48 h a...

The physiological consequences of activating corticotropin-releasing factor receptor type 2 (CRF2) are not fully understood. The neuroanatomic distribution of this CRF receptor family member is consistent with roles in mediating the actions of CRF and similar ligands on food intake control and integrative aspects of stress-related behaviors. However, CRF2 expression in the adult rat is not infl...

In nondiabetic rodents, AMP-activated protein kinase (AMPK) plays a role in the glucose-sensing mechanism used by the ventromedial hypothalamus (VMH), a key brain region involved in the detection of hypoglycemia. However, AMPK is regulated by both hyper- and hypoglycemia, so whether AMPK plays a similar role in type 1 diabetes (T1DM) is unknown. To address this issue, we used four groups of chr...