Dataset Information

Glucoregulatory responses to hypothalamic preoptic area cooling.

ABSTRACT: Normal glucose homeostasis depends on the capacity of pancreatic ?-cells to adjust insulin secretion in response to a change of tissue insulin sensitivity. In cold environments, for example, the dramatic increase of insulin sensitivity required to ensure a sufficient supply of glucose to thermogenic tissues is offset by a proportionate reduction of insulin secretion, such that overall glucose tolerance is preserved. That these cold-induced changes of insulin secretion and insulin sensitivity are dependent on sympathetic nervous system (SNS) outflow suggests a key role for thermoregulatory neurons in the hypothalamic preoptic area (POA) in this metabolic response. As these POA neurons are themselves sensitive to changes in local hypothalamic temperature, we hypothesized that direct cooling of the POA would elicit the same glucoregulatory responses that we observed during cold exposure. To test this hypothesis, we used a thermode to cool the POA area, and found that as predicted, short-term (8-h) intense POA cooling reduced glucose-stimulated insulin secretion (GSIS), yet glucose tolerance remained unchanged due to an increase of insulin sensitivity. Longer-term (24-h), more moderate POA cooling, however, failed to inhibit GSIS and improved glucose tolerance, an effect associated with hyperthermia and activation of the hypothalamic-pituitary-adrenal axis, indicative of a stress response. Taken together, these findings suggest that POA cooling is sufficient to recapitulate key glucoregulatory responses to cold exposure.

SUBMITTER: Muta K

PROVIDER: S-EPMC6532776 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glucoregulatory responses to hypothalamic preoptic area cooling.

Muta Kenjiro K Matsen Miles E ME Acharya Nikhil K NK Stefanovski Darko D Bergman Richard N RN Schwartz Michael W MW Morton Gregory J GJ

Brain research 20190102

Normal glucose homeostasis depends on the capacity of pancreatic β-cells to adjust insulin secretion in response to a change of tissue insulin sensitivity. In cold environments, for example, the dramatic increase of insulin sensitivity required to ensure a sufficient supply of glucose to thermogenic tissues is offset by a proportionate reduction of insulin secretion, such that overall glucose tolerance is preserved. That these cold-induced changes of insulin secretion and insulin sensitivity are ...[more]

PMID: 30610874

Similar Datasets

Project description:Central endozepinergic signaling is implicated in glucose homeostasis. Ventromedial hypothalamic nucleus (VMN) metabolic monitoring governs glucose counter-regulation. VMN glucose-stimulatory nitric oxide (NO) and glucose-inhibitory γ-aminobutyric acid (GABA) neurons express the energy gauge 5'-AMP-activated protein kinase (AMPK). Current research addresses the premise that the astrocyte glio-peptide octadecaneuropeptide (ODN) imposes sex-dimorphic control of metabolic sensor activity and neurotransmitter signaling in these neurons. The ODN G-protein coupled-receptor antagonist cyclo(1-8)[DLeu5]OP (LV-1075) was administered intracerebroventricularly (icv) to euglycemic rats of each sex; additional groups were pretreated icv with the ODN isoactive surrogate ODN11-18 (OP) before insulin-induced hypoglycemia. Western blotting of laser-catapult-microdissected VMN NO and GABA neurons showed that hypoglycemia caused OP-reversible augmentation of phospho-, e.g., activated AMPK and nitric oxide synthase (nNOS) expression in rostral (female) or middle (male) VMN segments or ODN-dependent suppression of nNOS in male caudal VMN. OP prevented hypoglycemic down-regulation of glutamate decarboxylase profiles in female rat rostral VMN, without affecting AMPK activity. LV-1075 treatment of male, not female rats elevated plasma glucagon and corticosterone concentrations. Moreover, OP attenuated hypoglycemia-associated augmentation of these hormones in males only. Results identify, for each sex, regional VMN metabolic transmitter signals that are subject to endozepinergic regulation. Directional shifts and gain-or-loss of ODN control during eu- versus hypoglycemia infer that VMN neuron receptivity to or post-receptor processing of this stimulus may be modulated by energy state. In male, counter-regulatory hormone secretion may be governed principally by ODN-sensitive neural pathways, whereas this endocrine outflow may be controlled by parallel, redundant ODN-dependent and -independent mechanisms in female.

Dataset Information

Glucoregulatory responses to hypothalamic preoptic area cooling.

Publications

Glucoregulatory responses to hypothalamic preoptic area cooling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets