Insulin blunts the response of glucose-excited neurons in the ventrolateral-ventromedial hypothalamic nucleus to decreased glucose

Victoria E. Cotero, Vanessa H. Routh

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Insulin signaling is dysfunctional in obesity and diabetes. Moreover, central glucose-sensing mechanisms are impaired in these diseases. This is associated with abnormalities in hypothalamic glucose-sensing neurons. Glucose-sensing neurons reside in key areas of the brain involved in glucose and energy homeostasis, such as the ventromedial hypothalamus (VMH). Our results indicate that insulin opens the KATP channel on VMH GE neurons in 5, 2.5, and 0.1 mM glucose. Furthermore, insulin reduced the sensitivity of VMH GE neurons to a decrease in extracellular glucose level from 2.5 to 0.1 mM. This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 μM). Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons. These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway. Furthermore, these data are consistent with the role of insulin as a satiety factor. That is, in the presence of insulin, glucose levels must decline further before GE neurons respond. Thus, the set point for detection of glucose deficit and initiation of compensatory mechanisms would be lowered.

Original languageEnglish (US)
Pages (from-to)E1101-E1109
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume296
Issue number5
DOIs
StatePublished - May 2009

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Keywords

  • Adenosine 5′-monophosphate-activated protein kinase
  • Adenosine 5′-triphosphate-sensitive K channel
  • Electrophysiology
  • Phosphatidylinositol 3-kinase

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