Skip to main content

High-Fat Programming of β-Cell Dysfunction

  • Living reference work entry
  • First Online:
Islets of Langerhans, 2. ed.
  • 124 Accesses

Abstract

High saturated fat intake contributes to insulin resistance, β-cell dysfunction, and type 2 diabetes. Developmental programming refers to a stimulus or insult during critical periods of life which includes fetal and subsequent early neonatal life. Programming alters progeny physiology and metabolism with immediate, transient, and durable effects. Maternal nutrition and metabolic state in gestation and lactation shapes progeny development and health. However, paternal nutrition and metabolic state also shapes progeny outcomes, albeit to a lesser extent. A high saturated fat diet ingested by mothers during gestation and/or lactation presents a nutritional insult that induces diabetogenic changes in progeny physiology and metabolism. High-fat programming is induced by maternal high saturated fat intake during defined periods of gestation and/or lactation and programs the physiology and metabolism of the progeny throughout life. This more recently adopted form of developmental programming reflects society in both affluent and developing countries. High-fat programming induces adverse changes in β-cell development and function in neonatal, weanling, and adolescent progeny. These changes are characterized by compromised β-cell development and function, evident by altered expression of key factors that maintain the β-cell phenotype. High-fat programming likely prompts β-cell dysfunction and eventual type 2 diabetes. Dietary consumption, limited in high saturated fat content, particularly in fetal and early postnatal life should be adopted in progeny. Healthy parental nutrition and metabolism pre-, during, and postconception, particularly maternal, should be maintained to enhance progeny health outcomes. These early intervention strategies may prevent the onset of metabolic disease.

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

Access this chapter

Institutional subscriptions

References

  • Ackermann AM, Gannon M (2007) Molecular regulation of pancreatic β-cell mass development, maintenance, and expansion. J Mol Endocrinol 38:193–206

    Article  PubMed  CAS  Google Scholar 

  • Anderson JW, Kendall CW, Jenkins DJ (2003) Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr 22:331–339

    Article  PubMed  Google Scholar 

  • Ashcroft FM, Rorsman P (2012) Diabetes mellitus and the beta cell: the last ten years. Cell 148:1160–1171

    Article  PubMed  CAS  Google Scholar 

  • Bhargava SK, Sachdev HS, Fall CH, Osmond C, Lakshmy R, Barker DJ, Biswas SK, Ramji S, Prabhakaran D, Reddy KS (2004) Relation of serial changes in childhood body mass index to impaired glucose tolerance in young adulthood. N Engl J Med 350:865–875

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Brunner Y, Schvartz D, Priego-Capote F, Coute Y, Sanchez JC (2009) Glucotoxicity and pancreatic proteomics. J Proteomics 71:576–591

    Article  PubMed  CAS  Google Scholar 

  • Cai EP, Casimir M, Schroer SA, Luk CT, Shi SY, Choi D, Dai XQ, Hajmrle C, Spigelman AF, Zhu D, Gaisano HY, MacDonald PE, Woo M (2012) In vivo role of focal adhesion kinase in regulating pancreatic beta-cell mass and function through insulin signaling, actin dynamics, and granule trafficking. Diabetes 61:1708–1718

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cerf ME (2007) High fat diet modulation of glucose sensing in the beta-cell. Med Sci Monit 13:RA12–RA17

    PubMed  CAS  Google Scholar 

  • Cerf ME (2011) Parental high-fat programming of offspring development, health and beta-cells. Islets 3:118–120

    Article  PubMed  Google Scholar 

  • Cerf ME (2012) Developmental programming, hyperglycemia and metabolic outcomes. Nova Science, Hauppauge, pp 73–84

    Google Scholar 

  • Cerf ME, Louw J (2008) High fat-induced programming of beta-cell development and function in neonatal and weanling offspring. Transworld Research Network, Kerala, pp 133–158

    Google Scholar 

  • Cerf ME, Louw J (2010) High fat programming induces glucose intolerance in weanling Wistar rats. Horm Metab Res 42:307–310

    Article  PubMed  CAS  Google Scholar 

  • Cerf ME, Williams K, Nkomo XI, Muller CJ, Du Toit DF, Louw J, Wolfe-Coote SA (2005) Islet cell response in the neonatal rat after exposure to a high-fat diet during pregnancy. Am J Physiol Regul Integr Comp Physiol 288:R1122–R1128

    Article  PubMed  CAS  Google Scholar 

  • Cerf ME, Muller CJ, Du Toit DF, Louw J, Wolfe-Coote SA (2006) Hyperglycaemia and reduced glucokinase expression in weanling offspring from dams maintained on a high fat diet. Br J Nutr 95:391–396

    Article  PubMed  CAS  Google Scholar 

  • Cerf ME, Williams K, Chapman CS, Louw J (2007) Compromised beta-cell development and beta-cell dysfunction in weanling offspring from dams maintained on a high-fat diet during gestation. Pancreas 34:347–353

    Article  PubMed  CAS  Google Scholar 

  • Cerf ME, Chapman CS, Muller CJ, Louw J (2009) Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal wistar rats. Metabolism 58:1787–1792

    Article  PubMed  CAS  Google Scholar 

  • Cerf ME, Chapman CS, Louw J (2012) High-fat programming of hyperglycemia, hyperinsulinemia, insulin resistance, hyperleptinemia, and altered islet architecture in 3-month-old wistar rats. ISRN Endocrinol 2012:627270

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen C, Hosokawa H, Bumbalo LM, Leahy JL (1994) Regulatory effects of glucose on the catalytic activity and cellular content of glucokinase in the pancreatic beta cell. Study using cultured rat islets. J Clin Invest 94:1616–1620

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Donath MY, Halban PA (2004) Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia 47:581–589

    Article  PubMed  CAS  Google Scholar 

  • Donath MY, Gross DJ, Cerasi E, Kaiser N (1999) Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48:738–744

    Article  PubMed  CAS  Google Scholar 

  • Dubois M, Vacher P, Roger B, Huyghe D, Vandewalle B, Kerr-Conte J, Pattou F, Moustaid- Moussa N, Lang J (2007) Glucotoxicity inhibits late steps of insulin exocytosis. Endocrinology 148:1605–1614

    Article  PubMed  CAS  Google Scholar 

  • Ehses JA, Perren A, Eppler E, Ribaux P, Pospisilik JA, Maor-Cahn R, Gueripel X, Ellingsgaard H, Schneider MK, Biollaz G, Fontana A, Reinecke M, Homo-Delarche F, Donath MY (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356–2370

    Article  PubMed  CAS  Google Scholar 

  • Ferreira MR, Lombardo YB, Chicco A (2010) Beta-cell adaptation/dysfunction in an animal model of dyslipidemia and insulin resistance induced by the chronic administration of a sucrose-rich diet. Islets 2:367–373

    Article  Google Scholar 

  • Giacca A, Xiao C, Oprescu AI, Carpentier AC, Lewis GF (2011) Lipid-induced pancreatic beta-cell dysfunction: focus on in vivo studies. Am J Physiol Endocrinol Metab 300:E255–E262

    Article  PubMed  CAS  Google Scholar 

  • Gluckman PD, Hanson MA (2004a) The developmental origins of the metabolic syndrome. Trends Endocrinol Metab 15:183–187

    Article  PubMed  CAS  Google Scholar 

  • Gluckman PD, Hanson MA (2004b) Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res 56:311–317

    Article  PubMed  Google Scholar 

  • Gniuli D, Calcagno A, Caristo ME, Mancuso A, Macchi V, Mingrone G, Vettor R (2008) Effects of high-fat diet exposure during fetal life on type 2 diabetes development in the progeny. J Lipid Res 49:1936–1945

    Article  PubMed  CAS  Google Scholar 

  • Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA (2007) Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res 61:5R–10R

    Article  PubMed  Google Scholar 

  • Grasemann C, Devlin MJ, Rzeczkowska PA, Herrmann R, Horsthemke B, Hauffa BP, Grynpas M, Alm C, Bouxsein ML, Palmert MR (2012) Parental diabetes: the Akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring. PLoS One 7:e50210

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gregorio BM, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB (2013) Maternal high-fat diet is associated with altered pancreatic remodelling in mice offspring. Eur J Nutr 52:759–769

    Article  PubMed  CAS  Google Scholar 

  • Gremlich S, Bonny C, Waeber G, Thorens B (1997) Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels. J Biol Chem 272:30261–30269

    Article  PubMed  CAS  Google Scholar 

  • Heywood WE, Mian N, Milla PJ, Lindley KJ (2004) Programming of defective rat pancreatic beta-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods. Clin Sci (Lond) 107:37–45

    Article  CAS  Google Scholar 

  • Jansson N, Nilsfelt A, Gellerstedt M, Wennergren M, Rossander-Hulthen L, Powell TL, Jansson T (2008) Maternal hormones linking maternal body mass index and dietary intake to birth weight. Am J Clin Nutr 87:1743–1749

    PubMed  CAS  Google Scholar 

  • Jorns A, Tiedge M, Ziv E, Shafrir E, Lenzen S (2002) Gradual loss of pancreatic beta-cell insulin, glucokinase and GLUT2 glucose transporter immunoreactivities during the time course of nutritionally induced type-2 diabetes in Psammomys obesus (sand rat). Virchows Arch 440:63–69

    Article  PubMed  CAS  Google Scholar 

  • Kasuga M (2006) Insulin resistance and pancreatic beta cell failure. J Clin Invest 116:1756–1760

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Khaldi MZ, Guiot Y, Gilon P, Henquin JC, Jonas JC (2004) Increased glucose sensitivity of both triggering and amplifying pathways of insulin secretion in rat islets cultured for 1 wk in high glucose. Am J Physiol Endocrinol Metab 287:E207–E217

    Article  PubMed  CAS  Google Scholar 

  • Kim JW, Yoon KH (2011) Glucolipotoxicity in pancreatic beta-cells. Diabetes Metab J 35:444–450

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim Y, Iwashita S, Tamura T, Tokuyama K, Suzuki M (1995) Effect of high-fat diet on the gene expression of pancreatic GLUT2 and glucokinase in rats. Biochem Biophys Res Commun 208:1092–1098

    Article  PubMed  CAS  Google Scholar 

  • Kiraly MA, Bates HE, Kaniuk NA, Yue JT, Brumell JH, Matthews SG, Riddell MC, Vranic M (2008) Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of beta-cell function. Am J Physiol Endocrinol Metab 294:E271–E283

    Article  PubMed  CAS  Google Scholar 

  • Kulkarni RN, Mizrachi EB, Ocana AG, Stewart AF (2012) Human beta-cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes 61:2205–2213

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • LeRoith D (2002) Beta-cell dysfunction and insulin resistance in type 2 diabetes: role of metabolic and genetic abnormalities. Am J Med 113:3S–11S

    Article  PubMed  CAS  Google Scholar 

  • Li D, Yin X, Zmuda EJ, Wolford CC, Dong X, White MF, Hai T (2008) The repression of IRS2 gene by ATF3, a stress-inducible gene, contributes to pancreatic beta-cell apoptosis. Diabetes 57:635–644

    Article  PubMed  CAS  Google Scholar 

  • Ludvik B, Nolan JJ, Baloga J, Sacks D, Olefsky J (1995) Effect of obesity on insulin resistance in normal subjects and patients with NIDDM. Diabetes 44:1121–1125

    Article  PubMed  CAS  Google Scholar 

  • Masiello P (2006) Animal models of type 2 diabetes with reduced pancreatic beta-cell mass. Int J Biochem Cell Biol 38:873–893

    Article  PubMed  CAS  Google Scholar 

  • Muoio DM, Newgard CB (2008) Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9:193–205

    Article  PubMed  CAS  Google Scholar 

  • Navarro-Tableros V, Fiordelisio T, Hernandez-Cruz A, Hiriart M (2007) Physiological development of insulin secretion, calcium channels and GLUT2 expression of pancreatic rat β-cells. Am J Physiol Endocrinol Metab 292:E1018–E1029

    Article  PubMed  CAS  Google Scholar 

  • Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467:963–966

    Article  PubMed  CAS  Google Scholar 

  • Park JH, Stoffers DA, Nicholls RD, Simmons RA (2008) Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 118:2316–2324

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pick A, Clark J, Kubstrup C, Levisetti M, Pugh W, Bonner-Weir S, Polonsky KS (1998) Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat. Diabetes 47:358–364

    Article  PubMed  CAS  Google Scholar 

  • Poitout V, Robertson RP (2002) Minireview: secondary beta-cell failure in type 2 diabetes - a convergence of glucotoxicity and lipotoxicity. Endocrinology 143:339–342

    Article  PubMed  CAS  Google Scholar 

  • Poitout V, Robertson RP (2008) Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 29:351–366

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Popkin BM (2001) Nutrition in transition: the changing global nutrition challenge. Asia Pac J Clin Nutr 10:S13–S18

    Article  PubMed  Google Scholar 

  • Portha B, Chavey A, Movassat J (2011) Early-life origins of type 2 diabetes: fetal programming of the beta-cell mass. Exp Diabetes Res 2011:105076

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Prentice AM, Moore SE (2005) Early programming of adult diseases in resource poor countries. Arch Dis Child 90:429–432

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Prentki M, Nolan CJ (2006) Islet beta cell failure in type 2 diabetes. J Clin Invest 116:1802–1812

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Prentki M, Joly E, El-Assaad W, Roduit R (2002) Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. Diabetes 51:S405–S413

    Article  PubMed  CAS  Google Scholar 

  • Reimer MK, Ahren B (2002) Altered beta-cell distribution of pdx-1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6 J mice. Diabetes 51:S138–S143

    Article  PubMed  CAS  Google Scholar 

  • Reusens B, Theys N, Dumortier O, Goosse K, Remacle C (2011) Maternal malnutrition programs the endocrine pancreas in progeny. Am J Clin Nutr 94:1824S–1829S

    Article  PubMed  CAS  Google Scholar 

  • Rhodes CJ (2005) Type 2 diabetes-a matter of beta-cell life and death? Science 307:380–384

    Article  PubMed  CAS  Google Scholar 

  • Ruderman N, Prentki M (2004) AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 3:340–351

    Article  PubMed  CAS  Google Scholar 

  • Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148:852–871

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Siebel AL, Mibus A, De Blasio MJ, Westcott KT, Morris MJ, Prior L, Owens JA, Wlodek ME (2008) Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring. Endocrinology 149:3067–3076

    Article  PubMed  CAS  Google Scholar 

  • Skelly RH, Bollheimer LC, Wicksteed BL, Corkey BE, Rhodes CJ (1998) A distinct difference in the metabolic stimulus–response coupling pathways for regulating proinsulin biosynthesis and insulin secretion that lies at the level of a requirement for fatty acyl moieties. Biochem J 331:553–561

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sone H, Kagawa Y (2005) Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia 48:58–67

    Article  PubMed  CAS  Google Scholar 

  • Terauchi Y, Sakura H, Yasuda K, Iwamoto K, Takahashi N, Ito K, Kasai H, Suzuki H, Ueda O, Kamada N (1995) Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose. J Biol Chem 270:30253–30256

    Article  PubMed  CAS  Google Scholar 

  • Terauchi Y, Takamoto I, Kubota N, Matsui J, Suzuki R, Komeda K, Hara A, Toyoda Y, Miwa I, Aizawa S, Tsutsumi S, Tsubamoto Y, Hashimoto S, Eto K, Nakamura A, Noda M, Tobe K, Aburatani H, Nagai R, Kadowaki T (2007) Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance. J Clin Invest 117:246–257

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Utzschneider KM, Carr DB, Hull RL, Kodama K, Shofer JB, Retzlaff BM, Knopp RH, Kahn SE (2004) Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function. Diabetes 53:2867–2872

    Article  PubMed  CAS  Google Scholar 

  • Van Raalte DH, Diamant M (2011) Glucolipotoxicity and beta cells in type 2 diabetes mellitus: target for durable therapy? Diabetes Res Clin Pract 93:S37–S46

    Article  PubMed  CAS  Google Scholar 

  • Weyer C, Bogardus C, Mott DM, Pratley RE (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391:900–904

    Article  PubMed  CAS  Google Scholar 

  • Zambrano E, Bautista CJ, Deas M, Martinez-Samayoa PM, Gonzalez-Zamorano M, Ledesma H, Morales J, Larrea F, Nathanielsz PW (2006) A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol 571:221–230

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marlon E. Cerf .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Cerf, M.E. (2014). High-Fat Programming of β-Cell Dysfunction. In: Islam, M. (eds) Islets of Langerhans, 2. ed.. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6884-0_3-6

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6884-0_3-6

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6884-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics