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Tytuł pozycji:

Central regulation of glucose metabolism in an insulin-dependent and -independent manner.

Tytuł :
Central regulation of glucose metabolism in an insulin-dependent and -independent manner.
Autorzy :
Fujikawa T; Center for Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
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Źródło :
Journal of neuroendocrinology [J Neuroendocrinol] 2021 Apr; Vol. 33 (4), pp. e12941. Date of Electronic Publication: 2021 Feb 18.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: <2010->: Malden, MA : Wiley & Sons
Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989-
References :
Bliss M. The Discover of Insulin. Chicago, IL: The University of Chicago Press; 1982.
Kahn CR, Roth J. Berson, Yalow, and the JCI: the agony and the ecstasy. J Clin Invest. 2004;114(8):1051-1054.
Bernard C. Leçons de Ohysiologie Experimentale Appliqués á là Medecine. Paris: J-B Baillière; 1854.
Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J. 1922;12(3):141-146.
Banting FGBC. Pancreatic extracts. J Lab Clin Med. 1922;115(2):254-272.
Schwartz MW, Seeley RJ, Tschop MH, et al. Cooperation between brain and islet in glucose homeostasis and diabetes. Nature. 2013;503(7474):59-66.
Kleinridders A, Ferris HA, Cai W, Kahn CR. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014;63(7):2232-2243.
Dodd GT, Tiganis T. Insulin action in the brain: roles in energy and glucose homeostasis. J Neuroendocrinol. 2017;29:https://doi.org/10.1111/jne.12513.
Ruud J, Steculorum SM, Bruning JC. Neuronal control of peripheral insulin sensitivity and glucose metabolism. Nat Commun. 2017;8:15259.
D'Souza AM, Neumann UH, Glavas MM, Kieffer TJ. The glucoregulatory actions of leptin. Mol Metab. 2017;6(9):1052-1065.
da Silva AA, Do carmo JM, Hall JE. CNS regulation of glucose homeostasis: role of the leptin-melanocortin system. Curr Diab Rep. 2020;20(7):29.
Fujikawa T, Coppari R. Living without insulin: the role of leptin signaling in the hypothalamus. Front Neurosci. 2015;9:https://doi.org/10.3389/fnins.2015.00108.
Thiebaud D, Jacot E, DeFronzo RA, Maeder E, Jequier E, Felber JP. The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes. 1982;31(11):957-963.
Titchenell PM, Lazar MA, Birnbaum MJ. Unraveling the Regulation of Hepatic Metabolism by Insulin. Trends Endocrinol Metab. 2017;28(7):497-505.
Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J Clin Invest. 2012;122(1):4-12.
Pocai A, Morgan K, Buettner C, Gutierrez-Juarez R, Obici S, Rossetti L. Central leptin acutely reverses diet-induced hepatic insulin resistance. Diabetes. 2005;54(11):3182-3189.
Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci. 2002;5(6):566-572.
Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med. 2002;8(12):1376-1382.
Konner AC, Janoschek R, Plum L, et al. Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab. 2007;5(6):438-449.
Gelling RW, Morton GJ, Morrison CD, et al. Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Cell Metab. 2006;3(1):67-73.
Blake CB, Smith BN. Insulin reduces excitation in gastric-related neurons of the dorsal motor nucleus of the vagus. Am J Physiol Regul Integr Comp Physiol. 2012;303(8):R807-R814.
Marks JL, Porte D Jr, Stahl WL, Baskin DG. Localization of insulin receptor mRNA in rat brain by in situ hybridization. Endocrinology. 1990;127(6):3234-3236.
Bruning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122-2125.
Kiecker C. The origins of the circumventricular organs. J Anat. 2018;232(4):540-553.
Romanov RA, Tretiakov EO, Kastriti ME, et al. Molecular design of hypothalamus development. Nature. 2020;582(7811):246-252.
Mickelsen LE, Bolisetty M, Chimileski BR, et al. Single-cell transcriptomic analysis of the lateral hypothalamic area reveals molecularly distinct populations of inhibitory and excitatory neurons. Nat Neurosci. 2019;22(4):642-656.
Campbell JN, Macosko EZ, Fenselau H, et al. A molecular census of arcuate hypothalamus and median eminence cell types. Nat Neurosci. 2017;20(3):484-496.
Cesarovic N, Jirkof P, Rettich A, Arras M. Implantation of radiotelemetry transmitters yielding data on ECG, heart rate, core body temperature and activity in free-moving laboratory mice. J Vis Exp. 2011;57:6371019.
Krashes MJ, Koda S, Ye C, et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest. 2011;121:1424-1428.
Steculorum SM, Ruud J, Karakasilioti I, et al. AgRP neurons control systemic insulin sensitivity via myostatin expression in brown adipose tissue. Cell. 2016;165:125-138.
Williams KW, Margatho LO, Lee CE, et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci. 2010;30(7):2472-2479.
Anderson EJ, Cakir I, Carrington SJ, et al. 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by alpha-MSH. J Mol Endocrinol. 2016;56(4):T157-T174.
King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav. 2006;87(2):221-244.
Choi YH, Fujikawa T, Lee J, Reuter A, Kim KW. Revisiting the ventral medial nucleus of the hypothalamus: the roles of SF-1 neurons in energy homeostasis. Front Neurosci. 2013;7:771.
Klockener T, Hess S, Belgardt BF, et al. High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nat Neurosci. 2011;14:911-918.
Filippi BM, Yang CS, Tang C, Lam TK. Insulin activates Erk1/2 signaling in the dorsal vagal complex to inhibit glucose production. Cell Metab. 2012;16(4):500-510.
Randle PJ. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev. 1998;14(4):263-283.
Green MH. Are fatty acids gluconeogenic precursors? J Nutr. 2020;150(9):2235-2238.
Tetrick MA, Odle J. What constitutes a gluconeogenic precursor? J Nutr. 2020;150(9):2239-2241.
Roden M, Price TB, Perseghin G, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest. 1996;97(12):2859-2865.
Liang H, Lum H, Alvarez A, Garduno-Garcia JJ, Daniel BJ, Musi N. A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects. PLoS One. 2018;13(4):e0195810.
Unger RH. Lipotoxic diseases. Annu Rev Med. 2002;53319-53336.
Perry RJ, Camporez JG, Kursawe R, et al. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell. 2015;160(4):745-758.
Titchenell PM, Quinn WJ, Lu M, et al. Direct hepatocyte insulin signaling is required for lipogenesis but is dispensable for the suppression of glucose production. Cell Metab. 2016;23(6):1154-1166.
Scherer T, O'Hare J, Diggs-Andrews K, et al. Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell Metab. 2011;13(2):183-194.
Scherer T, Lindtner C, O'Hare J, et al. Insulin regulates hepatic triglyceride secretion and lipid content via signaling in the brain. Diabetes. 2016;65(6):1511-1520.
Brown MS, Goldstein JL. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab. 2008;7(2):95-96.
Shin AC, Filatova N, Lindtner C, et al. Insulin receptor signaling in POMC, but not AgRP, neurons controls adipose tissue insulin action. Diabetes. 2017;66(6):1560-1571.
Brief DJ, Davis JD. Reduction of food intake and body weight by chronic intraventricular insulin infusion. Brain Res Bull. 1984;12(5):571-575.
Plata-Salaman CR, Oomura Y, Shimizu N. Dependence of food intake on acute and chronic ventricular administration of insulin. Physiol Behav. 1986;37(5):717-734.
Woods SC, Lotter EC, McKay LD, Porte D Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature. 1979;282(5738):503-505.
Jessen L, Clegg DJ, Bouman SD. Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats. Am J Physiol Regul Integr Comp Physiol. 2010;298(1):R43-50.
Mc Allister E, Pacheco-Lopez G, Woods SC, Langhans W. Inconsistencies in the hypophagic action of intracerebroventricular insulin in mice. Physiol Behav. 2015;151623-8.
Woods SC, Langhans W. Inconsistencies in the assessment of food intake. Am J Physiol Endocrinol Metab. 2012;303(12):E1408-E1418.
Filippi BM, Bassiri A, Abraham MA, Duca FA, Yue JT, Lam TK. Insulin signals through the dorsal vagal complex to regulate energy balance. Diabetes. 2014;63(3):892-899.
Konner AC, Hess S, Tovar S, et al. Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis. Cell Metab. 2011;13(6):720-728.
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002;5(6):514-516.
Renner DB, Svitak AL, Gallus NJ, Ericson ME, Frey WH 2nd, Hanson LR. Intranasal delivery of insulin via the olfactory nerve pathway. J Pharm Pharmacol. 2012;64(12):1709-1714.
Heni M, Kullmann S, Ketterer C, et al. Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions. Diabetologia. 2012;55(6):1773-1782.
Coates PA, Ismail IS, Luzio SD, et al. Intranasal insulin: the effects of three dose regimens on postprandial glycaemic profiles in type II diabetic subjects. Diabet Med. 1995;12(3):235-239.
Dash S, Xiao C, Morgantini C, Koulajian K, Lewis GF. Intranasal insulin suppresses endogenous glucose production in humans compared with placebo in the presence of similar venous insulin concentrations. Diabetes. 2015;64(3):766-774.
Ott V, Lehnert H, Staub J, Wonne K, Born J, Hallschmid M. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia. Diabetes. 2015;64(3):760-765.
Ramnanan CJ, Saraswathi V, Smith MS, et al. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs. J Clin Invest. 2011;121(9):3713-3723.
Pederson BA, Cope CR, Schroeder JM, et al. Exercise capacity of mice genetically lacking muscle glycogen synthase: in mice, muscle glycogen is not essential for exercise. J Biol Chem. 2005;280(17):17260-17265.
Ivy JL. Role of carbohydrate in physical activity. Clin Sports Med. 1999;18(3):469-484.
Baldwin KM, Reitman JS, Terjung RL, Winder WW, Holloszy JO. Substrate depletion in different types of muscle and in liver during prolonged running. Am J Physiol. 1973;225(5):1045-1050.
Fujikawa T, Chuang JC, Sakata I, Ramadori G, Coppari R. Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice. Proc Natl Acad Sci USA. 2010;107(40):17391-17396.
German JP, Thaler JP, Wisse BE, et al. Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology. 2011;152(2):394-404.
Fujikawa T, Berglund ED, Patel VR, et al. Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin. Cell Metab. 2013;18(3):431-444.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425-432.
Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87-91.
White RT, Damm D, Hancock N, et al. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem. 1992;267(13):9210-9213.
Rosen BS, Cook KS, Yaglom J, et al. Adipsin and complement factor D activity: an immune-related defect in obesity. Science. 1989;244(4911):1483-1487.
Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263-1271.
Gautron L, Elmquist JK. Sixteen years and counting: an update on leptin in energy balance. J Clin Invest. 2011;121(6):2087-2093.
Hill JW, Elmquist JK, Elias CF. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab. 2008;294(5):E827-E832.
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995;269(5223):546-549.
Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543-546.
Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269:540-543.
Sivitz WI, Walsh SA, Morgan DA, Thomas MJ, Haynes WG. Effects of leptin on insulin sensitivity in normal rats. Endocrinology. 1997;138(8):3395-3401.
Barzilai N, Wang J, Massilon D, Vuguin P, Hawkins M, Rossetti L. Leptin selectively decreases visceral adiposity and enhances insulin action. J Clin Invest. 1997;100(12):3105-3110.
Schwartz MW, Baskin DG, Bukowski TR, et al. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes. 1996;45(4):531-535.
Yu X, Park BH, Wang MY, Wang ZV, Unger RH. Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci USA. 2008;105(37):14070-14075.
Wang MY, Chen L, Clark GO, et al. Leptin therapy in insulin-deficient type I diabetes. Proc Natl Acad Sci USA. 2010;107(11):4813-4819.
Thorel F, Nepote V, Avril I, et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature. 2010;464(7292):1149-1154.
Neumann UH, Denroche HC, Mojibian M, Covey SD, Kieffer TJ. Insulin knockout mice have extended survival but volatile blood glucose levels on leptin therapy. Endocrinology. 2016;157(3):1007-1012.
Szabat M, Page MM, Panzhinskiy E, et al. Reduced insulin production relieves endoplasmic reticulum stress and induces beta cell proliferation. Cell Metab. 2016;23:179-193.
Lee Y, Berglund ED, Wang MY, et al. Metabolic manifestations of insulin deficiency do not occur without glucagon action. Proc Natl Acad Sci USA. 2012;109:14972-14976.
Conarello SL, Jiang G, Mu J, et al. Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia. Diabetologia. 2007;50(1):142-150.
Lee Y, Berglund ED, Yu X, et al. Hyperglycemia in rodent models of type 2 diabetes requires insulin-resistant alpha cells. Proc Natl Acad Sci USA. 2014;111(36):13217-13222.
Pearson MJ, Unger RH, Holland WL. Clinical trials, triumphs, and tribulations of glucagon receptor antagonists. Diabetes Care. 2016;39(7):1075-1077.
Kazda CM, Ding Y, Kelly RP, et al. Evaluation of efficacy and safety of the glucagon receptor antagonist LY2409021 in patients with type 2 diabetes: 12- and 24-week phase 2 studies. Diabetes Care. 2016;39(7):1241-1249.
German JP, Wisse BE, Thaler JP, et al. Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. Diabetes. 2010;59(7):1626-1634.
Meek TH, Matsen ME, Faber CL, et al. In Uncontrolled diabetes, hyperglucagonemia and ketosis result from deficient leptin action in the parabrachial nucleus. Endocrinology. 2018;159(4):1585-1594.
Perry RJ, Zhang XM, Zhang D, et al. Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nat Med. 2014;20(7):759-763.
Damond N, Thorel F, Moyers JS, et al. Blockade of glucagon signaling prevents or reverses diabetes onset only if residual beta-cells persist. Elife. 2016;5:e13828.
Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346(8):570-578.
Singha A, Palavicini JP, Pan M, et al. Leptin receptors in RIP-Cre(25Mgn) neurons mediate anti-dyslipidemia effects of leptin in insulin-deficient mice. Front Endocrinol. 2020;11:588447.
Ahima RS, Prabakaran D, Mantzoros C, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382(6588):250-252.
Perry RJ, Peng L, Abulizi A, Kennedy L, Cline GW, Shulman GI. Mechanism for leptin's acute insulin-independent effect to reverse diabetic ketoacidosis. J Clin Invest. 2017;127(2):657-669.
Morton GJ, Meek TH, Matsen ME, Schwartz MW. Evidence against hypothalamic-pituitary-adrenal axis suppression in the antidiabetic action of leptin. J Clin Invest. 2015;125(12):4587-4591.
da Silva AA, Hall JE, do Carmo JM. Leptin reverses hyperglycemia and hyperphagia in insulin deficient diabetic rats by pituitary-independent central nervous system actions. PLoS One. 2017;12(11):e0184805.
Minokoshi Y, Kim YB, Peroni OD, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339-343.
Buettner C, Muse ED, Cheng A, et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med. 2008;14(6):667-675.
Hackl MT, Furnsinn C, Schuh CM, et al. Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis. Nat Commun. 2019;10(1):2717.
Denroche HC, Kwon MM, Quong WL, et al. Leptin induces fasting hypoglycaemia in a mouse model of diabetes through the depletion of glycerol. Diabetologia. 2015;58(5):1100-1108.
Coppari R, Ichinose M, Lee CE, et al. The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metab. 2005;1(1):63-72.
Berglund ED, Vianna CR, Donato J Jr, et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest. 2012;122(3):1000-1009.
Huo L, Gamber K, Greeley S, et al. Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab. 2009;9(6):537-547.
Egan OK, Inglis MA, Anderson GM. Leptin signaling in AgRP neurons modulates puberty onset and adult fertility in mice. J Neurosci. 2017;37(14):3875-3886.
Goncalves GH, Li W, Garcia AV, Figueiredo MS, Bjorbaek C. Hypothalamic agouti-related peptide neurons and the central melanocortin system are crucial mediators of leptin's antidiabetic actions. Cell Rep. 2014;7(4):1093-1103.
Haque MS, Minokoshi Y, Hamai M, Iwai M, Horiuchi M, Shimazu T. Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes. 1999;481:706-712.
Meek TH, Matsen ME, Dorfman MD, et al. Leptin action in the ventromedial hypothalamic nucleus is sufficient, but not necessary, to normalize diabetic hyperglycemia. Endocrinology. 2013;154(9):3067-3076.
Vong L, Ye C, Yang Z, Choi B, Chua S Jr, Lowell BB. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron. 2011;71(1):142-154.
Xu J, Bartolome CL, Low CS, et al. Genetic identification of leptin neural circuits in energy and glucose homeostases. Nature. 2018;556(7702):505-509.
Singha AK, Yamaguchi J, Gonzalez NS, Ahmed N, Toney GM, Fujikawa T. Glucose-lowering by leptin in the absence of insulin does not fully rely on the central melanocortin system in male mice. Endocrinology. 2019;160(3):651-663.
Takahashi KA, Cone RD. Fasting induces a large, leptin-dependent increase in the intrinsic action potential frequency of orexigenic arcuate nucleus neuropeptide Y/Agouti-related protein neurons. Endocrinology. 2005;146(3):1043-1047.
van de Wall E, Leshan R, Xu AW, et al. Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology. 2008;149(4):1773-1785.
Xiao E, Xia-Zhang L, Vulliemoz NR, Ferin M, Wardlaw SL. Agouti-related protein stimulates the hypothalamic-pituitary-adrenal (HPA) axis and enhances the HPA response to interleukin-1 in the primate. Endocrinology. 2003;144(5):1736-1741.
Atasoy D, Betley JN, Su HH, Sternson SM. Deconstruction of a neural circuit for hunger. Nature. 2012;488(7410):172-177.
Krashes MJ, Shah BP, Madara JC, et al. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature. 2014;507(7491):238-242.
Lu XY, Barsh GS, Akil H, Watson SJ. Interaction between alpha-melanocyte-stimulating hormone and corticotropin-releasing hormone in the regulation of feeding and hypothalamo-pituitary-adrenal responses. J Neurosci. 2003;23(21):7863-7872.
Scott MM, Lachey JL, Sternson SM, et al. Leptin targets in the mouse brain. J Comp Neurol. 2009;514(5):518-532.
Nijenhuis WA, Oosterom J, Adan RA. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol. 2001;15(1):164-171.
Haskell-Luevano C, Monck EK. Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Regul Pept. 2001;99(1):1-7.
Ollmann MM, Wilson BD, Yang YK, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997;278(5335):135-138.
Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005;123(3):493-505.
Berglund ED, Liu T, Kong X, et al. Melanocortin 4 receptors in autonomic neurons regulate thermogenesis and glycemia. Nat Neurosci. 2014;17(7):911-913.
Shah BP, Vong L, Olson DP, et al. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. Proc Natl Acad Sci USA. 2014;111(36):13193-13198.
Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518(7538): 197-206.
Meek TH, Matsen ME, Damian V, Cubelo A, Chua SC Jr, Morton GJ. Role of melanocortin signaling in neuroendocrine and metabolic actions of leptin in male rats with uncontrolled diabetes. Endocrinology. 2014;155(11):4157-4167.
da Silva AA, Spradley FT, Granger JP, Hall JE, do Carmo JM. Brain-mediated antidiabetic, anorexic, and cardiovascular actions of leptin require melanocortin-4 receptor signaling. J Neurophysiol. 2015;113(7):2786-2791.
Mehran AE, Templeman NM, Brigidi GS, et al. Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metab. 2012;16(6):723-737.
Wicksteed B, Brissova M, Yan W, et al. Conditional gene targeting in mouse pancreatic ss-Cells: analysis of ectopic Cre transgene expression in the brain. Diabetes. 2010;59(12):3090-3098.
Covey SD, Wideman RD, McDonald C, et al. The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis. Cell Metab. 2006;4(4):291-302.
Soedling H, Hodson DJ, Adrianssens AE, et al. Limited impact on glucose homeostasis of leptin receptor deletion from insulin- or proglucagon-expressing cells. Mol Metab. 2015;4(9):619-630.
Denroche HC, Kwon MM, Glavas MM, et al. The role of autonomic efferents and uncoupling protein 1 in the glucose-lowering effect of leptin therapy. Mol Metab. 2016;5(8):716-724.
da Silva AA, Hall JE, Moak SP, et al. Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin. Am J Physiol Endocrinol Metab. 2017;312(5):E420-E428.
Coleman DL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia. 1973;9(4):294-298.
Castellano JM, Mosher KI, Abbey RJ, et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature. 2017;544(7651):488-492.
Saladin R, De Vos P, Guerre-Millo M, et al. Transient increase in obese gene expression after food intake or insulin administration. Nature. 1995;377(6549):527-529.
Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1(11):1155-1161.
Reitman ML, Arioglu E, Gavrilova O, Taylor SI. Lipoatrophy revisited. Trends Endocrinol Metab. 2000;11(10):410-416.
Brown RJ, Valencia A, Startzell M, et al. Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy. J Clin Invest. 2018;128(8):3504-3516.
Toyoshima Y, Gavrilova O, Yakar S, et al. Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes. Endocrinology. 2005;146(9):4024-4035.
Rossetti L, Massillon D, Barzilai N, et al. Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J Biol Chem. 1997;272(44):27758-27763.
Chinookoswong N, Wang JL, Shi ZQ. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes. 1999;48(7):1487-1492.
Koch C, Augustine RA, Steger J, et al. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity. J Neurosci. 2010;30(48):16180-16187.
Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Rep. 2012;13(12):1079-1086.
Williams KW, Scott MM, Elmquist JK. Modulation of the central melanocortin system by leptin, insulin, and serotonin: co-ordinated actions in a dispersed neuronal network. Eur J Pharmacol. 2011;660(1):2-12.
Lieu L, Chau D, Afrin S, et al. Effects of metabolic state on the regulation of melanocortin circuits. Physiol Behav. 2020;224:113039.
Huang Y, He Z, Gao Y, et al. Phosphoinositide 3-kinase is integral for the acute activity of leptin and insulin in male arcuate NPY/AgRP neurons. J Endocr Soc. 2018;2(6):518-532.
Al-Qassab H, Smith MA, Irvine EE, et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab. 2009;10(5):343-354.
Hill JW, Williams KW, Ye C, et al. Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest. 2008;118(5):1796-1805.
Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci. 2000;3(8):757-758.
Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford ML. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature. 1997;390(6659):521-525.
Carey M, Lontchi-Yimagou E, Mitchell W, et al. Central KATP channels modulate glucose effectiveness in humans and rodents. Diabetes. 2020;69(6):1140-1148.
Vasandani C, Clark GO, Adams-Huet B, Quittner C, Garg A. Efficacy and safety of metreleptin therapy in patients with type 1 diabetes: a pilot study. Diabetes Care. 2017;40(5):694-697.
Contributed Indexing :
Keywords: central nervous system; glucose metabolism; hypothalamus; insulin; leptin
Entry Date(s) :
Date Created: 20210218 Latest Revision: 20210419
Update Code :
20210419
DOI :
10.1111/jne.12941
PMID :
33599044
Czasopismo naukowe
The central nervous system (CNS) contributes significantly to glucose homeostasis. The available evidence indicates that insulin directly acts on the CNS, in particular the hypothalamus, to regulate hepatic glucose production, thereby controlling whole-body glucose metabolism. Additionally, insulin also acts on the brain to regulate food intake and fat metabolism, which may indirectly regulate glucose metabolism. Studies conducted over the last decade have found that the CNS can regulate glucose metabolism in an insulin-independent manner. Enhancement of central leptin signalling reverses hyperglycaemia in insulin-deficient rodents. Here, I review the mechanisms by which central insulin and leptin actions regulate glucose metabolism. Although clinical studies have shown that insulin treatment is currently indispensable for managing diabetes, unravelling the neuronal mechanisms underlying the central regulation of glucose metabolism will pave the way for the design of novel therapeutic drugs for diabetes.
(© 2021 British Society for Neuroendocrinology.)

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