Hypothalamic Control of Hepatic Glucose Production and Its Potential Role in Insulin Resistance

Buettner, Christoph; Camacho, Raul C.

doi:10.1016/j.ecl.2008.09.001

Cited by 28 publications

(18 citation statements)

References 115 publications

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“…Hypothalamic insulin controls hepatic and adipose tissue metabolism via the autonomic nervous system (Buettner and Camacho, 2008; Scherer et al, 2011). To examine a potential role of hypothalamic insulin signaling in regulating BCAA metabolism that occurs independent of counter-regulatory hormones, we infused insulin (2µU) or vehicle (artificial cerebrospinal fluid; aCSF) into the MBH of SD rats over 6h (as described above).…”

Section: Resultsmentioning

confidence: 99%

Brain Insulin Lowers Circulating BCAA Levels by Inducing Hepatic BCAA Catabolism

et al. 2014

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Summary Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in non-human primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs, and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

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Section: Resultsmentioning

confidence: 99%

Brain Insulin Lowers Circulating BCAA Levels by Inducing Hepatic BCAA Catabolism

et al. 2014

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“…Recent data have shown that insulin can exert this effect by acting on the MBH, with mice lacking the neuronal insulin receptor exhibiting uncontrolled lipolysis and decreased de novo lipogenesis in WAT [204]. Thus, insulin action within the brain suppresses basal WAT HSL activation, a marker of sympathetic outflow to WAT [13,204,205].…”

Section: Insulinmentioning

confidence: 93%

Hypothalamic-autonomic control of energy homeostasis

et al. 2015

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Regulation of energy homeostasis is tightly controlled by the central nervous system (CNS). Several key areas such as the hypothalamus and brainstem receive and integrate signals conveying energy status from the periphery, such as leptin, thyroid hormones, and insulin, ultimately leading to modulation of food intake, energy expenditure (EE), and peripheral metabolism. The autonomic nervous system (ANS) plays a key role in the response to such signals, innervating peripheral metabolic tissues, including brown and white adipose tissue (BAT and WAT), liver, pancreas, and skeletal muscle. The ANS consists of two parts, the sympathetic and parasympathetic nervous systems (SNS and PSNS). The SNS regulates BAT thermogenesis and EE, controlled by central areas such as the preoptic area (POA) and the ventromedial, dorsomedial, and arcuate hypothalamic nuclei (VMH, DMH, and ARC). The SNS also regulates lipid metabolism in WAT, controlled by the lateral hypothalamic area (LHA), VMH, and ARC. Control of hepatic glucose production and pancreatic insulin secretion also involves the LHA, VMH, and ARC as well as the dorsal vagal complex (DVC), via splanchnic sympathetic and the vagal parasympathetic nerves. Muscle glucose uptake is also controlled by the SNS via hypothalamic nuclei such as the VMH. There is recent evidence of novel pathways connecting the CNS and ANS. These include the hypothalamic AMP-activated protein kinase-SNS-BAT axis which has been demonstrated to be a key modulator of thermogenesis. In this review, we summarize current knowledge of the role of the ANS in the modulation of energy balance.

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“…Under euglycemic clamped conditions with basal insulin and glucose levels, neither insulin [8], glucose [162], nor fatty acids [68] infused into the MBH alter skeletal muscle glucose fluxes. However, large ICV glucose infusions inhibit muscle glycogen synthesis under hyperinsulinemic conditions [163], suggesting that either the CNS requires both elevated insulin and glucose to modulate skeletal muscle uptake or that these effects are pharmacological.…”

Section: Cns Control Of Skeletal Muscle Uptakementioning

confidence: 99%

Hypothalamic control of energy and glucose metabolism

Sisley

Sandoval

2011

Rev Endocr Metab Disord

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The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

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Hypothalamic Control of Hepatic Glucose Production and Its Potential Role in Insulin Resistance

Cited by 28 publications

References 115 publications

Brain Insulin Lowers Circulating BCAA Levels by Inducing Hepatic BCAA Catabolism

Brain Insulin Lowers Circulating BCAA Levels by Inducing Hepatic BCAA Catabolism

Hypothalamic-autonomic control of energy homeostasis

Hypothalamic control of energy and glucose metabolism

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