Abstract
Appetite and satiety are subject to complex regulation, with neuroendocrine mechanisms
playing an important role. The central nervous system is attracting increasing attention
as a target tissue for many hormones such as leptin, PYY3-36, ghrelin, glucagon-like-peptide
1 and many others. Among its many well-known functions, insulin is also a potent anorexigenic
hormone, and insulin receptors are widely distributed throughout the central nervous
system. One way to advance our understanding of central nervous regulation of hunger
and satiety in humans is to develop suitable neuroimaging techniques for use in various
clinical and experimental conditions. Several studies have been performed using functional
magnetic resonance imaging and positron emission tomography to identify areas of the
brain that are differentially activated by alteration of the feeding state. These
preliminary data are taking shape as a complex neuronal network involving the hypothalamus,
thalamus, limbic and paralimbic areas including the insular cortex and the anterior
cingulate gyrus and the orbitofrontal cortex. Continuous efforts to understand hormonal
effects on these pathways may advance our understanding of human obesity.
Key words
Insulin - central nervous system - appetite and satiety - neuroimaging
References
- 1
Biessels GJ, Kamal A, Urban IJ, Spruijt BM, Erkelens DW, Gispen WH.
Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic
rats: effects of insulin treatment.
Brain Res.
1998;
800
125-135
- 2
Bingham EM, Hopkins D, Smith D, Pernet A, Hallett W, Reed L, Marsden PK, Amiel SA.
The role of insulin in human brain glucose metabolism: an 18fluoro-deoxyglucose positron
emission tomography study.
Diabetes.
2002;
51
3384-3390
- 3
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
514-516
- 4
Boyd FT, Clarke DW, Muther TF, Raizada MK.
Insulin receptors and insulin modulation of norepinephrine uptake in neuronal cultures
from rat brain.
J Biol Chem.
1985;
260
15880-15884
- 5
Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W,
Müller-Wieland D, Kahn CR.
Role of brain insulin receptor in control of body weight and reproduction.
Science.
2000;
289
2122-2125
- 6
Craft S, Newcomer J, Kanne S, gogo-Jack S, Cryer P, Sheline Y, Luby J, gogo-Jack A,
Alderson A.
Memory improvement following induced hyperinsulinemia in Alzheimer's disease.
Neurobiol Aging.
1996;
17
123-130
- 7
Cranston I, Marsden P, Matyka K, Evans M, Lomas J, Sonksen P, Maisey M, Amiel SA.
Regional differences in cerebral blood flow and glucose utilization in diabetic man:
the effect of insulin.
J Cereb Blood Flow Metab.
1998;
18
130-140
- 8
de Graaf C, Blom WA, Smeets PA, Stafleu A, Hendriks HF.
Biomarkers of satiation and satiety.
Am J Clin Nutr.
2004;
79
946-961
- 9
Del Parigi A, Gautier JF, Chen K, Salbe AD, Ravussin E, Reiman E, Tataranni PA.
Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans
using positron emission tomography.
Ann N Y Acad Sci.
2002;
967
389-397
- 10
Eastman RC, Carson RE, Gordon MR, Berg GW, Lillioja S, Larson SM, Roth J.
Brain glucose metabolism in noninsulin-dependent diabetes mellitus: a study in Pima
Indians using positron emission tomography during hyperinsulinemia with euglycemic
glucose clamp.
J Clin Endocrinol Metab.
1990;
71
1602-1610
- 11
Gottfried JA, O’Doherty J, Dolan RJ.
Encoding predictive reward value in human amygdala and orbitofrontal cortex.
Science.
2003;
301
1104-1107
- 12
Hallschmid M, Benedict C, Schultes B, Fehm HL, Born J, Kern W.
Intranasal insulin reduces body fat in men but not in women.
Diabetes.
2004;
53
3024-3029
- 13
Hallschmid M, Schultes B, Marshall L, Molle M, Kern W, Bredthauer J, Fehm HL, Born J.
Transcortical direct current potential shift reflects immediate signaling of systemic
insulin to the human brain.
Diabetes.
2004;
53
2202-2208
- 14
Hasselbalch SG, Knudsen GM, Videbaek C, Pinborg LH, Schmidt JF, Holm S, Paulson OB.
No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism
in humans.
Diabetes.
1999;
48
1915-1921
- 15
Havrankova J, Roth J, Brownstein M.
Insulin receptors are widely distributed in the central nervous system of the rat.
Nature.
1978;
272
827-829
- 16
Hopkins DF, Williams G.
Insulin receptors are widely distributed in human brain and bind human and porcine
insulin with equal affinity.
Diabet Med.
1997;
14
1044-1050
- 17
Kern W, Born J, Schreiber H, Fehm HL.
Central nervous system effects of intranasally administered insulin during euglycemia
in men.
Diabetes.
1999;
48
557-563
- 18
Kern W, Peters A, Fruehwald-Schultes B, Deininger E, Born J, Fehm HL.
Improving influence of insulin on cognitive functions in humans.
Neuroendocrinology.
2001;
74
270-280
- 19
Killgore WD, Young AD, Femia LA, Bogorodzki P, Rogowska J, Yurgelun-Todd DA.
Cortical and limbic activation during viewing of high- versus low-calorie foods.
Neuroimage.
2003;
19
1381-1394
- 20
Killgore WD, Yurgelun-Todd DA.
Body mass predicts orbitofrontal activity during visual presentations of high-calorie
foods.
Neuroreport.
2005;
16
859-863
- 21
Niswender KD, Schwartz MW.
Insulin and leptin revisited: adiposity signals with overlapping physiological and
intracellular signaling capabilities.
Front Neuroendocrinol.
2003;
24
1-10
- 22
Obici S, Zhang BB, Karkanias G, Rossetti L.
Hypothalamic insulin signaling is required for inhibition of glucose production.
Nat Med.
2002;
8
1376-1382
- 23
Porte D, Seeley RJ, Woods SC, Baskin DG, Figlewicz DP, Schwartz MW.
Obesity, diabetes and the central nervous system.
Diabetologia.
1998;
41
863-881
- 24
Rosenthal JM, Amiel SA, Yaguez L, Bullmore E, Hopkins D, Evans M, Pernet A, Reid H,
Giampietro V, Andrew CM, Suckling J, Simmons A, Williams SCR.
The Effect of Acute Hypoglycemia on Brain Function and Activation: A Functional Magnetic
Resonance Imaging Study.
Diabetes.
2001;
50
1618-1626
- 25
Rotte M, Baerecke C, Pottag G, Klose S, Kanneberg E, Heinze HJ, Lehnert H.
Insulin affects the neuronal response in the medial temporal lobe in humans.
Neuroendocrinology.
2005;
81
49-55
- 26
Schulingkamp RJ, Pagano TC, Hung D, Raffa RB.
Insulin receptors and insulin action in the brain: review and clinical implications.
Neurosci Biobehav Rev.
2000;
24
855-872
- 27
Schwartz MW, Bergman RN, Kahn SE, Taborsky GJ, Fisher LD, Sipols AJ, Woods SC, Steil GM,
Porte D.
Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate
compartment in dogs. Quantitative aspects and implications for transport.
J Clin Invest.
1991;
88
1272-1281
- 28
Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG.
Central nervous system control of food intake.
Nature.
2000;
404
661-671
- 29
Simmons WK, Martin A, Barsalou LW.
Pictures of Appetizing Foods Activate Gustatory Cortices for Taste and Reward.
Cereb Cortex.
2005;
15
1602-1608
- 30
Tataranni PA, DelParigi A.
Functional neuroimaging: a new generation of human brain studies in obesity research.
Obes Rev.
2003;
4
229-238
- 31 Tschritter O, Preissl H, Fritsche A, Haap M, Shirkavand F, Birbaumer N, Häring H,
Stumvoll M. Decreased insulin response in the cerebral cortex of healthy overweight
humans. Diabetes und Stoffwechsel 13(P-258), 119. (Conference Proceeding) 2004
- 32
Vandenbergh J, Dupont P, Fischler B, Bormans G, Persoons P, Janssens J, Tack J.
Regional brain activation during proximal stomach distention in humans: A positron
emission tomography study.
Gastroenterology.
2005;
128
564-573
- 33
Wang GJ, Volkow ND, Telang F, Jayne M, Ma J, Rao M, Zhu W, Wong CT, Pappas NR, Geliebter A,
Fowler JS.
Exposure to appetitive food stimuli markedly activates the human brain.
Neuroimage.
2004;
21
1790-1797
- 34
Watson GS, Peskind ER, Asthana S, Purganan K, Wait C, Chapman D, Schwartz MW, Plymate S,
Craft S.
Insulin increases CSF Abeta42 levels in normal older adults.
Neurology.
2003;
60
1899-1903
- 35
Woods SC, Lotter EC, McKay LD, Porte D.
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight
of baboons.
Nature.
1979;
282
503-505
Correspondence
Michael StumvollMD
Professor of Medicine·University of Leipzig·III. Medical Department
Philipp-Rosenthal-Str. 27·04103 Leipzig·Germany
Telefon: +49/341/971 33 80
Fax: +49/341/971 33 89
eMail: michael.stumvoll@medizin.uni-leipzig.de