Journal ArticleDOI
Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats.
David Spanswick,Mark A. Smith,S. Mirshamsi,Vanessa H. Routh,Vanessa H. Routh,Michael L.J. Ashford +5 more
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TLDR
It is demonstrated that insulin, like leptin, hyperpolarizes lean rat hypothalamic glucose-responsive neurons by opening KATP channels, which suggest hypothalamic KatP channel function is crucial to physiological regulation of food intake and body weight.Abstract:
Insulin and leptin receptors are present in hypothalamic regions that control energy homeostasis, and these hormones reduce food intake and body weight in lean, but not obese, Zucker rats. Here we demonstrate that insulin, like leptin, hyperpolarizes lean rat hypothalamic glucose-responsive (GR) neurons by opening KATP channels. These findings suggest hypothalamic K ATP channel function is crucial to physiological regulation of food intake and body weight.read more
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Central nervous system control of food intake and body weight
TL;DR: This new information provides a biological context within which to consider the global obesity epidemic and identifies numerous potential avenues for therapeutic intervention and future research.
Journal ArticleDOI
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Yasuhiko Minokoshi,Thierry Alquier,Noboru Furukawa,Young-Bum Kim,Anna Lee,Bingzhong Xue,James Mu,Fabienne Foufelle,Pascal Ferré,Morris J. Birnbaum,Bettina J. Stuck,Barbara B. Kahn +11 more
TL;DR: Hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance, and inhibition of hypothalamic AM PK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects.
Journal ArticleDOI
Anatomy and regulation of the central melanocortin system.
TL;DR: Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
Journal ArticleDOI
The need to feed: Homeostatic and hedonic control of eating
TL;DR: The role played in homeostatic regulation of feeding by systemic mediators such as leptin and ghrelin are examined, which act on brain systems utilizing neuropeptide Y, agouti-related peptide, melanocortins, orexins, and melanin concentrating hormone, among other mediators.
Journal ArticleDOI
Hypothalamic insulin signaling is required for inhibition of glucose production.
TL;DR: The results reveal a new site of action of insulin on glucose production and suggest that hypothalamic insulin resistance can contribute to hyperglycemia in type 2 diabetes mellitus.
References
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Phosphoinositide 3-kinase : the key switch mechanism in insulin signalling
TL;DR: Using mechanisms such as this, PI 3-kinase is able to act as a molecular switch to regulate the activity of serine/threonine-specific kinase cascades important in mediating insulin's effects on endpoint responses.
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Leptin receptor missense mutation in the fatty zucker rat
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Insulin in the brain: a hormonal regulator of energy balance.
TL;DR: Recent investigations indicate that “brain insulin” is derived largely from the circulation, and a growing body of evidence suggests that its delivery into the neuropil may be facilitated by a specialized BBB barrier.
Journal ArticleDOI
Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels
TL;DR: It is shown that leptin hyperpolarizes glucose-receptive hypothalamic neurons of lean Sprague–Dawley and Zucker rats, but is ineffective on neurons of obese Zucker (fa/fa ) rats, and single-channel recordings demonstrate that leptin activates an ATP-sensitive potassium (KATP) channel.
Journal ArticleDOI
Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats
Zhen Y. Jiang,You-Wei Lin,Allen Clemont,Edward P. Feener,Katherine D. Hein,Masahiko Igarashi,Teruaki Yamauchi,Morris F. White,George L. King +8 more
TL;DR: To the authors' knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in theascular tissues of obese Zucker rats.