sb-334867-a and Diabetes-Mellitus--Type-1

sb-334867-a has been researched along with Diabetes-Mellitus--Type-1* in 1 studies

Other Studies

1 other study(ies) available for sb-334867-a and Diabetes-Mellitus--Type-1

Article	Year
Perifornical hypothalamic orexin and serotonin modulate the counterregulatory response to hypoglycemic and glucoprivic stimuli. Diabetes, 2015, Volume: 64, Issue:1 Previous reports suggested an important role for serotonin (5-hydroxytryptamine [5-HT]) in enhancing the counterregulatory response (CRR) to hypoglycemia. To elucidate the sites of action mediating this effect, we initially found that insulin-induced hypoglycemia stimulates 5-HT release in widespread forebrain regions, including the perifornical hypothalamus (PFH; 30%), ventromedial hypothalamus (34%), paraventricular hypothalamus (34%), paraventricular thalamic nucleus (64%), and cerebral cortex (63%). Of these, we focused on the PFH because of its known modulation of diverse neurohumoral and behavioral responses. In awake, behaving rats, bilateral PFH glucoprivation with 5-thioglucose stimulated adrenal medullary epinephrine (Epi) release (3,153%) and feeding (400%), while clamping PFH glucose at postprandial brain levels blunted the Epi response to hypoglycemia by 30%. The PFH contained both glucose-excited (GE) and glucose-inhibited (GI) neurons; GE neurons were primarily excited, while GI neurons were equally excited or inhibited by 5-HT at hypoglycemic glucose levels in vitro. Also, 5-HT stimulated lactate production by cultured hypothalamic astrocytes. Depleting PFH 5-HT blunted the Epi (but not feeding) response to focal PFH (69%) and systemic glucoprivation (39%), while increasing PFH 5-HT levels amplified the Epi response to hypoglycemia by 32%. Finally, the orexin 1 receptor antagonist SB334867A attenuated both the Epi (65%) and feeding (47%) responses to focal PFH glucoprivation. Thus we have identified the PFH as a glucoregulatory region where both 5-HT and orexin modulate the CRR and feeding responses to glucoprivation. Topics: Animals; Astrocytes; Benzoxazoles; Blood Glucose; Cells, Cultured; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fornix, Brain; Hypoglycemia; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Midline Thalamic Nuclei; Naphthyridines; Neurons; Neuropeptides; Orexins; Paraventricular Hypothalamic Nucleus; Rats, Sprague-Dawley; Receptors, Neuropeptide; Serotonin; Urea; Ventromedial Hypothalamic Nucleus	2015

Article

Year

Perifornical hypothalamic orexin and serotonin modulate the counterregulatory response to hypoglycemic and glucoprivic stimuli.

Diabetes, 2015, Volume: 64, Issue:1

Previous reports suggested an important role for serotonin (5-hydroxytryptamine [5-HT]) in enhancing the counterregulatory response (CRR) to hypoglycemia. To elucidate the sites of action mediating this effect, we initially found that insulin-induced hypoglycemia stimulates 5-HT release in widespread forebrain regions, including the perifornical hypothalamus (PFH; 30%), ventromedial hypothalamus (34%), paraventricular hypothalamus (34%), paraventricular thalamic nucleus (64%), and cerebral cortex (63%). Of these, we focused on the PFH because of its known modulation of diverse neurohumoral and behavioral responses. In awake, behaving rats, bilateral PFH glucoprivation with 5-thioglucose stimulated adrenal medullary epinephrine (Epi) release (3,153%) and feeding (400%), while clamping PFH glucose at postprandial brain levels blunted the Epi response to hypoglycemia by 30%. The PFH contained both glucose-excited (GE) and glucose-inhibited (GI) neurons; GE neurons were primarily excited, while GI neurons were equally excited or inhibited by 5-HT at hypoglycemic glucose levels in vitro. Also, 5-HT stimulated lactate production by cultured hypothalamic astrocytes. Depleting PFH 5-HT blunted the Epi (but not feeding) response to focal PFH (69%) and systemic glucoprivation (39%), while increasing PFH 5-HT levels amplified the Epi response to hypoglycemia by 32%. Finally, the orexin 1 receptor antagonist SB334867A attenuated both the Epi (65%) and feeding (47%) responses to focal PFH glucoprivation. Thus we have identified the PFH as a glucoregulatory region where both 5-HT and orexin modulate the CRR and feeding responses to glucoprivation.

Topics: Animals; Astrocytes; Benzoxazoles; Blood Glucose; Cells, Cultured; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fornix, Brain; Hypoglycemia; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Midline Thalamic Nuclei; Naphthyridines; Neurons; Neuropeptides; Orexins; Paraventricular Hypothalamic Nucleus; Rats, Sprague-Dawley; Receptors, Neuropeptide; Serotonin; Urea; Ventromedial Hypothalamic Nucleus

2015