Skip to main content
SpringerLink
Log in

Molekulare Grundlagen altersspezifischer Erkrankungen des Endokriniums

  • Chapter
Molekularmedizinische Grundlagen von altersspezifischen Erkrankungen

Part of the book series: Molekulare Medizin ((MOLMED))

  • 178 Accesses

Zusammenfassung

Der als Somatopause, Menopause bzw. Andropause bezeichnete Abfall der Serumkonzentration von Wachstumshormonen und Sexualsteroiden im Alter ist mit Veränderungen der Körperzusammensetzung und von kognitiven wie physischen Fähigkeiten verbunden, die mit selektiven Störungen der jeweiligen Hormonachsen in der Jugend gut vergleichbar sind. Da eine Hormonersatztherapie die Symptomatik zumindest teilweise normalisieren kann, ist diskutiert worden, dass auch Alterungsvorgänge wesentlich durch die Veränderung der humoralen Steuerung beeinflusst werden. Sowohl der Ausfall der somatotropen wie der gonadotropen Achse führt in der Jugend zu einem Abbau der Muskulatur und einer Zunahme der Körperfettmasse. Vergleichbare Verschiebungen der Körperzusammensetzung finden sich bei physiologischen Alterungsvorgängen, welche bereits in der 2. bis 3. Lebensdekade erkennbar sind. Dies wird belegt durch Querschnittsuntersuchungen wie das Monica-Projekt, aber auch durch Longitudinalstudien (Mayo Clinic, Baltimore, Longitudinal Study on Ageing), in deren Verlauf gesunde Erwachsene über mehrere Jahrzehnte hinsichtlich ihrer Körperzusammensetzung mit sehr präzisen Messmethoden untersucht wurden (Forbes u. Reina 1970, Liese et al. 2001, Metter et al. 2002, Roy et al. 2002). Als Ergebnis dieser verschiedenen Ansätze fand sich eine Abnahme der Muskelmasse zwischen dem 20. und 60. Lebensjahr von 5–10 kg bei einem Gewichtsanstieg von insgesamt 10–15 kg. Diese Daten unterstützen die deutliche Verschiebung der Körperzusammensetzung mit einem erheblichen Verlust von Muskelmasse und einer ausgeprägten Akkumulation von Körperfett im physiologischen Alterungsprozess. Eng mit der Verminderung der Muskelmasse ist auch eine Verschlechterung der Muskelfunktion verbunden, welche die Gebrechlichkeit alter Menschen erhöht, Stürze leichter möglich macht und damit eine Pflegeabhängigkeit bei älteren Menschen auslösen kann. Ziel der vorliegenden Übersicht soll es sein, die Veränderung der Sexualsteroide beim Mann, der Wachstumshormonachse und von metabolischen Vorgängen in der altersspezifischen Physiologie mit Bezug auf die bisher bekannten molekularen Mechanismen darzustellen.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  • Almind K, Bjorbaek C, Vestergaard H, Hansen T, Echwald S, Pedersen O (1993) Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet 342:828–832

    PubMed  CAS  Google Scholar 

  • Altshuler D, Hirschhorn JN, Klannemark M, et al(2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76–80

    PubMed  CAS  Google Scholar 

  • Arvat E, Broglio F, Ghigo E (2000) Insulin-like growth factor I: implications in aging. Drugs Aging 16:29–40

    PubMed  CAS  Google Scholar 

  • Auwerx J (1999) PPARgamma, the ultimate thrifty gene. Diabetologia 42:1033–1049

    PubMed  CAS  Google Scholar 

  • Barsh GS, Schwartz MW (2002) Genetic approaches to studying energy balance: perception and integration. Nat Rev Genet 3:589–600

    PubMed  CAS  Google Scholar 

  • Bartke A (1998) Growth hormone and aging. Endocrine 8:103–108

    PubMed  CAS  Google Scholar 

  • Bartke A (2000) Delayed aging in Ames dwarf mice. Relationships to endocrine function and body size. Results Probi Cell Differ 29:181–202

    CAS  Google Scholar 

  • Batterham RL, Cowley MA, Small CJ, et al(2002) Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418:650–654

    PubMed  CAS  Google Scholar 

  • Beld van den AW, Lamberts SW (2002) Endocrine aspects of healthy ageing in men. Novartis Found Symp 242:3–16

    PubMed  Google Scholar 

  • Beld van den AW, Bots ML, Janssen JA, Pols HA, Lamberts SW, Grobbee DE (2003) Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol 157:25–31

    PubMed  Google Scholar 

  • Bell GI, Pilkis SJ, Weber IT, Polonsky KS (1996) Glucokinase mutations, insulin secretion, and diabetes mellitus. Annu Rev Physiol 58:171–186

    PubMed  CAS  Google Scholar 

  • Beral V, Banks E, Reeves (2002) Evidence from randomised trials on the long-term effects of hormone replacement therapy. Lancet 360:942–944

    PubMed  Google Scholar 

  • Bjorbaek C, Hollenberg AN (2002) Leptin and melanocortin signaling in the hypothalamus. Vitam Horm 65:281–311

    PubMed  CAS  Google Scholar 

  • Boden G (1996) Fatty acids and insulin resistance. Diabetes Care 19:394–395

    PubMed  CAS  Google Scholar 

  • Boden G, Chen X, Ruiz J, White JV, Rossetti L (1994) Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93:2438–2446

    PubMed  CAS  Google Scholar 

  • Bonavera JJ, Swerdloff RS, Sinha Hakim AP, Lue YH, Wang C (1998) Aging results in attenuated gonadotropin releasing hormone-luteinizing hormone axis responsiveness to glutamate receptor agonist N-methyl-D-aspartate. J Neuroendocrinol 10:93–99

    PubMed  CAS  Google Scholar 

  • Brabant G, von zur Muhlen A, Wuster C, et al (2003) Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res 60(2):53–60

    PubMed  CAS  Google Scholar 

  • Brabant G, Horn R, Muhlen von zur A, et al(2000) Free and protein bound leptin are distinct and independently controlled factors in energy regulation. Diabetologia 43:438–442

    PubMed  CAS  Google Scholar 

  • Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384:33

    PubMed  CAS  Google Scholar 

  • Butler AA, Kesterson RA, Khong K, et al(2000) A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141:3518–3521

    PubMed  CAS  Google Scholar 

  • Carroll PV, Christ ER, Bengtsson BA, et al(1998) Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 83:382–395

    PubMed  CAS  Google Scholar 

  • Cheatham B, Volchuk A, Kahn CR, Wang L, Rhodes CJ, Klip A (1996) Insulin-stimulated translocation of GLUT4 glucose transporters requires SNARE-complex proteins. PNAS 93:15169–15173

    PubMed  CAS  Google Scholar 

  • Chen AS, Marsh DJ, Trumbauer ME, et al(2000) Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 26:97–102

    PubMed  CAS  Google Scholar 

  • Chen H, Hardy MP, Zirkin BR (2002) Age-related decreases in Leydig cell testosterone production are not restored by exposure to LH in vitro. Endocrinology 143:1637–1642

    PubMed  CAS  Google Scholar 

  • Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, Kaestner KH, et al (2001) Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ). Science 292:1728–1731

    PubMed  CAS  Google Scholar 

  • Clement K, Vaisse C, Lahlou N, et al(1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398–401

    PubMed  CAS  Google Scholar 

  • Clement S, Krause U, Desmedt F, et al(2001) The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409:92–97

    PubMed  CAS  Google Scholar 

  • Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141:2608–2613

    PubMed  CAS  Google Scholar 

  • Cseh K, Winkler G, Melczer Z, Baranyi E (2000) The role of tumour necrosis factor (TNF)-alpha resistance in obesity and insulin resistance. Diabetologia 43:525

    PubMed  CAS  Google Scholar 

  • Davey HW, Park SH, Grattan DR, McLachlan MJ, Waxman DJ (1999) STAT5b-deficient mice are growth hormone pulse-resistant. Role of STAT5b in sex-specific liver p450 expression. J Biol Chem 274:35331–35336

    PubMed  CAS  Google Scholar 

  • Davidson MB (1979) The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly. Metabolism 28:688–705

    PubMed  CAS  Google Scholar 

  • Della-Zuana O, Presse F, Ortola C, Duhault J, Nahon JL, Levens N (2002) Acute and chronic administration of melanin-concentrating hormone enhances food intake and body weight in Wistar and Sprague-Dawley rats. Int J Obes Relat Metab Disord 26:1289–1295

    PubMed  CAS  Google Scholar 

  • Erickson JC, Clegg KE, Palmiter RD (1996) Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381:415–421

    PubMed  CAS  Google Scholar 

  • Eriksson J, Franssila-Kallunki A, Ekstrand A, et al(1989) Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med 321:337–343

    PubMed  CAS  Google Scholar 

  • Fajans SS, Bell GI, Polonsky KS (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 345:971–980

    PubMed  CAS  Google Scholar 

  • Fantin VR, Wang Q, Lienhard GE, Keller SR (2000) Mice lacking insulin receptor substrate 4 exhibit mild defects in growth, reproduction, and glucose homeostasis. Am J Physiol Endocrinol Metab 278:127–133

    Google Scholar 

  • Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G, Smith U (1996) Insulin action and age. European Group for the Study of Insulin Resistance (EGIR). Diabetes 45:947–953

    PubMed  CAS  Google Scholar 

  • Fink G, Sumner BE, McQueen JK, Wilson H, Rosie R (1998) Sex steroid control of mood, mental state and memory. Clin Exp Pharmacol Physiol 25:764–775

    PubMed  CAS  Google Scholar 

  • Flurkey K, Papaconstantinou J, Miller RA, Harrison DE (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98:6736–6741

    PubMed  CAS  Google Scholar 

  • Forbes GB, Reina JC (1970) Adult lean body mass declines with age: some longitudinal observations. Metabolism 19:653–663

    PubMed  CAS  Google Scholar 

  • Froguel P, Vaxillaire M, Sun F, et al(1992) Close linkage of glucokinase locus on chromosome 7p to early-onset noninsulin-dependent diabetes mellitus. Nature 356:162–164

    PubMed  CAS  Google Scholar 

  • Fruman DA, Mauvais-Jarvis F, Pollard DA, et al(2000) Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat Genet 26:379–382

    PubMed  CAS  Google Scholar 

  • Garg A, Misra A (2002) Hepatic steatosis, insulin resistance, and adipose tissue disorders. J Clin Endocrinol Metab 87:3019–3022

    PubMed  CAS  Google Scholar 

  • Gebert CA, Park SH, Waxman DJ (1997) Regulation of signal transducer and activator of transcription (STAT) 5b activation by the temporal pattern of growth hormone stimulation. Mol Endocrinol 11:400–414

    PubMed  CAS  Google Scholar 

  • Gerbitz KD, Gempel K, Brdiczka D (1996) Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit. Diabetes 45:113–126

    PubMed  CAS  Google Scholar 

  • Gerbitz KD, Ouweland van den JM, Maassen JA, Jaksch M (1995) Mitochondrial diabetes mellitus: a review. Biochim Biophys Acta 1271:253–260

    PubMed  Google Scholar 

  • Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797

    PubMed  CAS  Google Scholar 

  • Gruenewald DA, Naai MA, Marck BT, Matsumoto AM (2000) Age-related decrease in hypothalamic gonadotropin-releasing hormone (GnRH) gene expression, but not pituitary responsiveness to GnRH, in the male Brown Norway rat. J Androl 21:72–84

    PubMed  CAS  Google Scholar 

  • Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM (1997) Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci USA 94:8878–8883

    PubMed  CAS  Google Scholar 

  • Hanis CL, Boerwinkle E, Chakraborty R, et al(1996) A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet 13:161–166

    PubMed  CAS  Google Scholar 

  • Hansen L, Hansen T, Vestergaard H, et al(1995) A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin. Hum Mol Genet 4:1313–1320

    PubMed  CAS  Google Scholar 

  • Hansen L, Reneland R, Berglund L, et al(2000) Polymorphism in the glycogen-associated regulatory subunit of type 1 protein phosphatase (PPP1R3) gene and insulin sensitivity. Diabetes 49:298–301

    PubMed  CAS  Google Scholar 

  • Hara J, Beuckmann CT, Nambu T, et al(2001) Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30:345–354

    PubMed  CAS  Google Scholar 

  • Harris MI, Eastman RC, Cowie CC, Flegal KM, Eberhardt MS (1997) Comparison of diabetes diagnostic categories in the U.S. population according to the 1997 American Diabetes Association and 1980-1985 World Health Organization diagnostic criteria. Diabetes Care 20:1859–1862

    PubMed  CAS  Google Scholar 

  • Harris MI, Flegal KM, Cowie CC, et al(1998) Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third Natlonal Health and Nutrition Examination Survey, 1988-1994. Diabetes Care 21:518–524

    PubMed  CAS  Google Scholar 

  • Hebebrand J, Fichter M, Gerber G, et al(2002) Genetic predisposition to obesity in bulimia nervosa: a mutation screen of the melanocortin-4 receptor gene. Mol Psychiatry 7:647–651

    PubMed  CAS  Google Scholar 

  • Hegele RA (2000) Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. Mol Genet Metab 71:539–544

    PubMed  CAS  Google Scholar 

  • Herbert J (1995) The age of dehydroepiandrosterone. Lancet 345:1193–1194

    PubMed  CAS  Google Scholar 

  • Hollopeter G, Erickson JC, Palmiter RD (1998) Role of neuropeptide Y in diet-, chemical-and genetic-induced obesity of mice. Int J Obes Relat Metab Disord 22:506–512

    PubMed  CAS  Google Scholar 

  • Holzenberger M, Dupont J, Ducos B, et al(2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–187

    PubMed  CAS  Google Scholar 

  • Horikawa Y, Iwasaki N, Hara M, et al(1997) Mutation in he-patocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 17:384–385

    PubMed  CAS  Google Scholar 

  • Horikawa Y, Oda N, Cox NJ, et al(2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 26:163–175

    PubMed  CAS  Google Scholar 

  • Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRSI-mediated inhibition of insulin receptor tyrosine kinase activity in TNFa and obesity-induced insulin resistance. Science 271:665–668

    PubMed  CAS  Google Scholar 

  • Howard AD, Feighner SD, Cully DF, et al(1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273:974–977

    PubMed  CAS  Google Scholar 

  • Inoue H, Ferrer J, Welling CM, et al(1996) Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians. Diabetes 45:825–831

    PubMed  CAS  Google Scholar 

  • Jackson RS, Creemers JW, Ohagi S, et al(1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303–306

    PubMed  CAS  Google Scholar 

  • Kadowaki T, Kadowaki H, Mori Y, et al(1994) A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med 330:962–968

    PubMed  CAS  Google Scholar 

  • Kahn CR, Flier JS, Bar RS, et al(1976) The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 294:739–745

    PubMed  CAS  Google Scholar 

  • Kalmijn S, Janssen JA, Pols HA, Lamberts SW, Breteler MM (2000) A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly. J Clin Endocrinol Metab 85:4551–4555

    PubMed  CAS  Google Scholar 

  • Katz EB, Stenbit AE, Hatton K, De Pinho R, Charron MJ (1995) Cardiac and adipose tissue abnormalities but not diabetes in mice deficient in GLUT4. Nature 377:151–155

    PubMed  CAS  Google Scholar 

  • Kaufmann S, Jones M, Culler FL, Jones KL (1986) Growth hormone deficiency in the Rothmund-Thomson syndrome. Am J Med Genet 23:861–868

    PubMed  CAS  Google Scholar 

  • Kimm SY, Glynn NW, Kriska AM, et al(2002) Decline in physical activity in black girls and white girls during adolescence. N Engl J Med 347:709–715

    PubMed  Google Scholar 

  • Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946

    PubMed  CAS  Google Scholar 

  • Kristensen P, Judge ME, Thim L, et al(1998) Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393:72–76

    PubMed  CAS  Google Scholar 

  • Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155–157

    PubMed  CAS  Google Scholar 

  • Kruszynska YT, Mukherjee R, Jow L, Dana S, Paterniti JR, Olefsky JM (1998) Skeletal muscle peroxisome proliferator-activated receptor-gamma expression in obesity and non-insulin-dependent diabetes mellitus. J Clin Invest 101:543–548

    PubMed  CAS  Google Scholar 

  • Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL (1994) Increasing prevalence of overweight among US adults. The Natlonal Health and Nutrition Examination Surveys, 1960 to 1991. JAMA 272:205–211

    PubMed  CAS  Google Scholar 

  • Landerman HM (1995) Is maturity-onset diabetes at young age (MODY) more common in Europe than previously assumed? Lancet 345:648

    Google Scholar 

  • Lanni A, Moreno M, Lombardi A, Lange de P, Goglia F (2001) Control of energy metabolism by iodothyronines. J Endocrinol Invest 24:897–913

    PubMed  CAS  Google Scholar 

  • Laron Z, Klinger B (1993) Body fat in Laron syndrome patients: effect of insulin-like growth factor I treatment. Horm Res 40:16–22

    PubMed  CAS  Google Scholar 

  • Larsen PJ, Vrang N, Tang-Christensen M, et al(2002) Ups and downs for neuropeptides in body weight homeostasis: pharmacological potential of cocaine amphetamine regulated transcript and pre-proglucagon-derived peptides. Eur J Pharmacol 440:159–172

    PubMed  CAS  Google Scholar 

  • Leifke E, Gorenoi V, Wichers C, Muhlen von zur A, Buren von E, Brabant G (2000) Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort. Clin Endocrinol (Oxf) 53:689–695

    CAS  Google Scholar 

  • Liese AD, Doring A, Hense HW, Keil U (2001) Five year changes in waist circumference, body mass index and obesity in Augsburg, Germany. Eur J Nutr 40:282–288

    PubMed  CAS  Google Scholar 

  • Lillioja S, Mott DM, Spraul M, et al(1993) Insulin resistance and insulin secretory dysfunction as precursors of noninsulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329:1988–1992

    PubMed  CAS  Google Scholar 

  • Liu SC, Wang Q, Lienhard GE, Keller SR (1999) Insulin receptor substrate 3 is not essential for growth or glucose homeostasis. J Biol Chem 274:18093–18099

    PubMed  CAS  Google Scholar 

  • Maccario M, Veldhuis JD, Broglio F, et al(2002) Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans. Eur J Endocrinol 146:310–318

    PubMed  Google Scholar 

  • Maeda N, Shimomura I, Kishida K, et al(2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8:731–737

    PubMed  CAS  Google Scholar 

  • Maffei M, Fei H, Lee GH, et al(1995) Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci USA 92:6957–6960

    PubMed  CAS  Google Scholar 

  • Mahtani MM, Widen E, Lehto M, et al(1996) Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families. Nat Genet 14:90–94

    PubMed  CAS  Google Scholar 

  • Malecki MT, Jhala US, Antonellis A, et al(1999) Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet 23:323–328

    PubMed  CAS  Google Scholar 

  • Marion E, Kaisaki PJ, Pouillon V, et al(2002) The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man. Diabetes 51:2012–2017

    PubMed  CAS  Google Scholar 

  • Matsuda M, Shimomura I, Sata M, et al(2002) Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 277:37487–37491

    PubMed  CAS  Google Scholar 

  • Matthaei S, Stumvoll M, Kellerer M, Haring HU (2000) Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 21:585–618

    PubMed  CAS  Google Scholar 

  • Metter EJ, Talbot LA, Schrager M, Conwit R (2002) Skeletal muscle strength as a predictor of all-cause mortality in healthy men. J Gerontol A Biol Sci Med Sci 57:359–365

    Google Scholar 

  • Mikuma N, Kumamoto Y, Maruta H, Nitta T (1994) Role of the hypothalamic opioidergic system in the control of gonadotropin secretion in elderly men. Andrologia 26:39–45

    PubMed  CAS  Google Scholar 

  • Moller DE (2000) Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11:212–217

    PubMed  CAS  Google Scholar 

  • Moller DE, Benecke H, Flier JS (1991) Biologic activities of naturally occurring human insulin receptor mutations. Evidence that metabolic effects of insulin can be mediated by a kinase-deficient insulin receptor mutant. J Biol Chem 266:10995–11001

    PubMed  CAS  Google Scholar 

  • Montague CT, Farooqi IS, Whitehead JP, et al(1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908

    PubMed  CAS  Google Scholar 

  • Morley JE, Perry HM 3rd, Miller DK (2002) Editorial: Something about frailty. J Gerontol A Biol Sci Med Sci 57:698–704

    Google Scholar 

  • Mulligan T, Iranmanesh A, Kerzner R, Demers LW, Veldhuis JD (1999) Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis. Eur J Endocrinol 141:257–266

    PubMed  CAS  Google Scholar 

  • Nance MA, Berry SA (1992) Cockayne syndrome: review of 140 cases. Am J Med Genet 42:68–84

    PubMed  CAS  Google Scholar 

  • Neel JV, Weder AB, Julius S (1998) Type II diabetes, essential hypertension, and obesity as „syndromes of impaired genetic homeostasis“: the „thrifty genotype“ hypothesis enters the 21st century. Perspect Biol Med 42:44–74

    PubMed  CAS  Google Scholar 

  • Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD (1987) Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia 30:763–768

    PubMed  CAS  Google Scholar 

  • Nishimura DY, Searby CC, Carmi R, et al(2001) Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2). Hum Mol Genet 10:865–874

    PubMed  CAS  Google Scholar 

  • Ollmann MM, Wilson BD, Yang YK, et al(1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135–138

    PubMed  CAS  Google Scholar 

  • Patel YM, Lane MD (1999) Role of calpain in adipocyte differentiation. PNAS 96:1279–1284

    PubMed  CAS  Google Scholar 

  • Petersen S, Rasch AC, Penshorn M, Beil FU, Schulte HM (2001) Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor. Endocrinology 142:2649–2659

    Google Scholar 

  • Randeva HS, Murray RD, Lewandowski KC, et al(2002) Differential effects of GH replacement on the components of the leptin system in GH-deficient individuals. J Clin Endocrinol Metab 87:798–804

    PubMed  CAS  Google Scholar 

  • Roy TA, Blackman MR, Harman SM, Tobin JD, Schrager M, Metter EJ (2002) Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men. Am J Physiol Endocrinol Metab 283:284–394

    Google Scholar 

  • Rubin CD, Reed B (1996) Twenty-four hour growth hormone secretion in a patient with Werner’s syndrome. Exp Gerontol 31:557–561

    PubMed  CAS  Google Scholar 

  • Rudman D, Feller AG, Nagraj HS, et al(1990) Effects of human growth hormone in men over 60 years old. N Engl J Med 323:1–6

    PubMed  CAS  Google Scholar 

  • Savage DB, Tan GD, Acerini CL, et al(2003) Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-γ. Diabetes 52:910–917

    PubMed  CAS  Google Scholar 

  • Schwartz MW, Morton GJ (2002) Obesity: keeping hunger at bay. Nature 418:595–597

    PubMed  CAS  Google Scholar 

  • Shackleton S, Lloyd DJ, Jackson SN, et al(2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet 24:153–156

    PubMed  CAS  Google Scholar 

  • Shaw JT, Lovelock PK, Resting JB, et al(1998) Novel susceptibility gene for late-onset NIDDM is localized to human chromosome 12q. Diabetes 47:1793–1796

    PubMed  CAS  Google Scholar 

  • Shimokata H, Muller DC, Fleg JL, Ziemba AW, Andres R (1991) Age as an independent determinant of glucose tolerance. Diabetes 40:44–51

    PubMed  CAS  Google Scholar 

  • Smith LK, Rice KM, Garner CW (1996) The insulin-induced down-regulation of IRS-1 in 3T3-L1 adipocytes is mediated by a calcium-dependent thiol protease. Mol Cell Endocrinol 122:81–92

    PubMed  CAS  Google Scholar 

  • Sohn EH, Wolden-Hanson T, Matsumoto AM (2002) Testosterone (T)-induced changes in arcuate nucleus cocaine-amphetamine-regulated transcript and NPY mRNA are attenuated in old compared to young male brown Norway rats: contribution of T to age-related changes in cocaineamphetamine-regulated transcript and NPY gene expression. Endocrinology 143:954–963

    PubMed  CAS  Google Scholar 

  • Steppan CM, Lazar MA (2002) Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 13:18–23

    PubMed  CAS  Google Scholar 

  • Stoffers DA, Ferrer J, Clarke WL, Habener JF (1997) Earlyonset type-II diabetes mellitus (M0DY4) linked to IPF1. Nat Genet 17:138–139

    PubMed  CAS  Google Scholar 

  • Stumvoll M, Haring H (2002) Resistin and adiponectin of mice and men. Obes Res 10:1197–1199

    PubMed  Google Scholar 

  • Tamemoto H, Kadowaki T, Tobe K, et al(1994) Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372:182–186

    PubMed  CAS  Google Scholar 

  • Terauchi Y, Tsuji Y, Satoh S, et al(1999) Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nat Genet 21:230–235

    PubMed  CAS  Google Scholar 

  • Tollet-Egnell P, Flores-Morales A, Stahlberg N, Malek RL, Lee N, Norstedt G (2001) Gene expression profile of the aging process in rat liver: normalizing effects of growth hormone replacement. Mol Endocrinol 15:308–318

    PubMed  CAS  Google Scholar 

  • Tritos NA, Maratos-Flier E (1999) Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone. Neuropeptides 33:339–349

    PubMed  CAS  Google Scholar 

  • Urban JH, Das I, Levine JE (1996) Steroid modulation of neuropeptide Y-induced luteinizing hormone releasing hormone release from median eminence fragments from male rats. Neuroendocrinology 63:112–119

    PubMed  CAS  Google Scholar 

  • Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610–614

    PubMed  CAS  Google Scholar 

  • Vaisse C, Clement K, Guy-Grand B, Froguel P (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 20:113–114

    PubMed  CAS  Google Scholar 

  • Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest 106:253–262

    PubMed  CAS  Google Scholar 

  • Veldhuis JD, Iranmanesh A, Mulligan T, Bowers CY (2002) Mechanisms of conjoint failure of the somatotropic and gonadal axes in ageing men. Novartis Found Symp 242:98–118

    PubMed  CAS  Google Scholar 

  • Velho G, Blanche H, Vaxillaire M, et al(1997) Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia 40:217–224

    PubMed  CAS  Google Scholar 

  • Villee DB, Nichols G Jr, Talbot NB (1969) Metabolic studies in two boys with classical progeria. Pediatrics 43:207–216

    PubMed  CAS  Google Scholar 

  • Wang C, Hikim AS, Ferrini M, et al(2002) Male reproductive ageing: using the brown Norway rat as a model for man. Novartis Found Symp 242:82–95

    PubMed  CAS  Google Scholar 

  • Waxman DJ, Pampori NA, Ram PA, Agrawal AK, Shapiro BH (1991) Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450. Proc Natl Acad Sci USA 88:6868–6872

    PubMed  CAS  Google Scholar 

  • Weyer C, Funahashi T, Tanaka S, et al(2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935

    PubMed  CAS  Google Scholar 

  • WHO (1985) Diabetes mellitus: report of a WHO Study Group. WHO Tech Rep Ser

    Google Scholar 

  • Withers DJ, Gutierrez JS, Towery H, et al(1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391:900–904

    PubMed  CAS  Google Scholar 

  • Wren AM, Seal LJ, Cohen MA, et al (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992

    PubMed  CAS  Google Scholar 

  • Xu H, Uysal KT, Becherer JD, Arner P, Hotamisligil GS (2002) Altered tumor necrosis factor-alpha (TNF-alpha) processing in adipocytes and increased expression of transmembrane TNF-alpha in obesity. Diabetes 51:1876–1883

    PubMed  CAS  Google Scholar 

  • Yamada K, Yuan X, Ishiyama S, et al(1998) Codon 972 polymorphism of the insulin receptor substrate-1 gene in impaired glucose tolerance and late-onset NIDDM. Diabetes Care 21:753–756

    PubMed  CAS  Google Scholar 

  • Yamagata K, Oda N, Kaisaki PJ, et al(1996) Mutations in the hepatocyte nuclear factor-1alpha gene in maturityonset diabetes of the young (MODY3). Nature 384:455–458

    PubMed  CAS  Google Scholar 

  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Jens Behrends
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georg Brabant
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13122, Berlin-Buch, Germany

    Detlev Ganten  & Klaus Ruckpaul  & 

  2. Instituto Universitario de Investigación Gerontológica, Diego de León 62, E-28006, Madrid, Germany

    Antonio Ruiz-Torres

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Behrends, J., Brabant, G. (2004). Molekulare Grundlagen altersspezifischer Erkrankungen des Endokriniums. In: Ganten, D., Ruckpaul, K., Ruiz-Torres, A. (eds) Molekularmedizinische Grundlagen von altersspezifischen Erkrankungen. Molekulare Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18741-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18741-4_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62272-4

  • Online ISBN: 978-3-642-18741-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation