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International Journal of Endocrinology
Volume 2012 (2012), Article ID 320482, 13 pages
http://dx.doi.org/10.1155/2012/320482
Pancreatic Function, Type 2 Diabetes, and Metabolism in Aging
1Department of Pediatrics, Divisions of Endocrinology and Geriatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2Department of Medicine, Divisions of Endocrinology and Geriatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Received 2 December 2011; Revised 15 February 2012; Accepted 2 March 2012
Academic Editor: Huan Cai
Copyright © 2012 Zhenwei Gong and Radhika H. Muzumdar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Linked References
- M. M. Engelgau, L. S. Geiss, J. B. Saaddine et al., “The evolving diabetes burden in the United States,” Annals of Internal Medicine, vol. 140, no. 11, pp. 945–950, 2004. View at Google Scholar · View at Scopus
- U. Gunasekaran and M. Gannon, “Type 2 diabetes and the aging pancreatic beta cell,” Aging, vol. 3, pp. 565–575, 2011. View at Google Scholar
- P. Iozzo, H. Beck-Nielsen, M. Laakso et al., “Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance,” The Journal of Clinical Endocrinology & Metabolism, vol. 84, pp. 863–868, 1999. View at Google Scholar
- C. C. Cowie, K. F. Rust, D. D. Byrd-Holt et al., “Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health and Nutrition Examination Survey 1999–2002,” Diabetes Care, vol. 29, no. 6, pp. 1263–1268, 2006. View at Publisher · View at Google Scholar · View at Scopus
- C. C. Cowie, K. F. Rust, E. S. Ford et al., “Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005-2006,” Diabetes Care, vol. 32, no. 2, pp. 287–294, 2009. View at Publisher · View at Google Scholar · View at Scopus
- G. M. Reaven, “Role of insulin resistance in human disease,” Diabetes, vol. 37, no. 12, pp. 1595–1607, 1988. View at Google Scholar · View at Scopus
- T. Kadowaki, “Insights into insulin resistance and type 2 diabetes from knockout mouse models,” Journal of Clinical Investigation, vol. 106, no. 4, pp. 459–465, 2000. View at Google Scholar · View at Scopus
- M. Chen, R. N. Bergman, G. Pacini, and D. Porte Jr., “Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta-cell function,” The Journal of Clinical Endocrinology & Metabolism, vol. 60, pp. 13–20, 1985. View at Google Scholar
- L. P. van der Heide, G. M. J. Ramakers, and M. P. Smidt, “Insulin signaling in the central nervous system: learning to survive,” Progress in Neurobiology, vol. 79, no. 4, pp. 205–221, 2006. View at Publisher · View at Google Scholar · View at Scopus
- A. M. Chang and J. B. Halter, “Aging and insulin secretion,” The Journal of Clinical Endocrinology & Metabolism, vol. 284, pp. E7–E12, 2003. View at Google Scholar
- K. M. Ramsey, K. F. Mills, A. Satoh, and S. I. Imai, “Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice,” Aging Cell, vol. 7, no. 1, pp. 78–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
- R. C. Cooksey, H. A. Jouihan, R. S. Ajioka et al., “Oxidative stress, β-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis,” Endocrinology, vol. 145, no. 11, pp. 5305–5312, 2004. View at Publisher · View at Google Scholar · View at Scopus
- E. Montanya, V. Nacher, M. Biarnes, and J. Soler, “Linear correlation between β-cell mass and body weight throughout the lifespan in Lewis rats. Role of β-cell hyperplasia and hypertrophy,” Diabetes, vol. 49, no. 8, pp. 1341–1346, 2000. View at Google Scholar · View at Scopus
- S. Y. Wang, P. A. Halban, and J. W. Rowe, “Effects of aging on insulin synthesis and secretion. Differential effects on preproinsulin messenger RNA levels, proinsulin biosynthesis, and secretion of newly made and preformed insulin in the rat,” Journal of Clinical Investigation, vol. 81, no. 1, pp. 176–184, 1988. View at Google Scholar · View at Scopus
- S. Del Guerra, R. Lupi, L. Marselli et al., “Functional and molecular defects of pancreatic islets in human type 2 diabetes,” Diabetes, vol. 54, no. 3, pp. 727–735, 2005. View at Publisher · View at Google Scholar · View at Scopus
- K. Ohtsubo, S. Takamatsu, M. T. Minowa, A. Yoshida, M. Takeuchi, and J. D. Marth, “Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes,” Cell, vol. 123, no. 7, pp. 1307–1321, 2005. View at Publisher · View at Google Scholar · View at Scopus
- C. Hou, D. Williams, J. Vicogne, and J. E. Pessin, “The glucose transporter 2 undergoes plasma membrane endocytosis and lysosomal degradation in a secretagogue-dependent manner,” Endocrinology, vol. 150, no. 9, pp. 4056–4064, 2009. View at Publisher · View at Google Scholar · View at Scopus
- J. Kramer, E. L. Moeller, A. Hachey, K. G. Mansfield, and L. M. Wachtman, “Differential expression of GLUT2 in pancreatic islets and kidneys of New and Old World nonhuman primates,” American Journal of Physiology, vol. 296, no. 3, pp. R786–R793, 2009. View at Publisher · View at Google Scholar · View at Scopus
- S. H. Ihm, H. J. Moon, J. G. Kang et al., “Effect of aging on insulin secretory function and expression of beta cell function-related genes of islets,” Diabetes Research and Clinical Practice, vol. 77, no. 3, supplement, pp. S150–S154, 2007. View at Publisher · View at Google Scholar · View at Scopus
- M. Ohneda, J. H. Johnson, L. R. Inman et al., “GLUT2 expression and function in β-cells of GK rats with NIDDM: dissociation between reductions in glucose transport and glucose-stimulated insulin secretion,” Diabetes, vol. 42, no. 7, pp. 1065–1072, 1993. View at Google Scholar · View at Scopus
- L. J. McCulloch, M. van de Bunt, M. Braun et al., “GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus,” Molecular Genetics and Metabolism, vol. 104, no. 4, pp. 648–653, 2011. View at Google Scholar
- M. Anello, R. Lupi, D. Spampinato et al., “Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients,” Diabetologia, vol. 48, no. 2, pp. 282–289, 2005. View at Publisher · View at Google Scholar · View at Scopus
- G. I. Bell, S. J. Pilkis, I. T. Weber, and K. S. Polonsky, “Glucokinase mutations, insulin secretion, and diabetes mellitus,” Annual Review of Physiology, vol. 58, pp. 171–186, 1996. View at Google Scholar · View at Scopus
- T. Frese, I. Bazwinsky, E. Muhlbauer, and E. Peschke, “Circadian and age-dependent expression patterns of GLUT2 and glucokinase in the pancreatic beta-cell of diabetic and nondiabetic rats,” Hormone and Metabolic Research, vol. 39, pp. 567–574, 2007. View at Google Scholar
- G. M. Reaven and P. D. Reaven, “Effect of age on glucose oxidation by isolated rat islets,” Diabetologia, vol. 18, no. 1, pp. 69–71, 1980. View at Google Scholar · View at Scopus
- R. C. Bonadonna, L. C. Groop, D. C. Simonson, and R. A. DeFronzo, “Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle,” American Journal of Physiology., vol. 266, no. 3, pp. E501–E509, 1994. View at Google Scholar · View at Scopus
- M. J. MacDonald, “High content of mitochondrial glycerol-3-phosphate dehydrogenase in pancreatic islets and its inhibition by diazoxide,” The Journal of Biological Chemistry, vol. 256, no. 16, pp. 8287–8290, 1981. View at Google Scholar · View at Scopus
- S. Azhar, H. Ho, E. P. Reaven, and G. M. Reaven, “Evidence of an age-related decline in mitochondrial glycerophosphate dehydrogenase activity of isolated rat islets,” Metabolism, vol. 32, no. 11, pp. 1019–1021, 1983. View at Google Scholar · View at Scopus
- H. P. T. Ammon, A. Fahmy, and M. Mark, “The effect of glucose on insulin release and ion movements in isolated pancreatic islets of rats in old age,” Journal of Physiology, vol. 384, pp. 347–354, 1987. View at Google Scholar · View at Scopus
- J. Lang, “Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion,” European Journal of Biochemistry, vol. 259, no. 1-2, pp. 3–17, 1999. View at Publisher · View at Google Scholar · View at Scopus
- R. Fernandez-Chacon and G. Alvarez de Toledo, “Cytosolic calcium facilitates release of secretory products after exocytotic vesicle fusion,” FEBS Letters, vol. 363, no. 3, pp. 221–225, 1995. View at Publisher · View at Google Scholar · View at Scopus
- R. Heidelberger, C. Heinemann, E. Neher, and G. Matthews, “Calcium dependence of the rate of exocytosis in a synaptic terminal,” Nature, vol. 371, no. 6497, pp. 513–515, 1994. View at Publisher · View at Google Scholar · View at Scopus
- G. Jacobsson, A. J. Bean, R. H. Scheller et al., “Identification of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 26, pp. 12487–12491, 1994. View at Publisher · View at Google Scholar · View at Scopus
- C. E. Kiraly-Borri, A. Morgan, R. D. Burgoyne, U. Weller, C. B. Wollheim, and J. Lang, “Soluble N-ethylmaleimide-sensitive-factor attachment protein and N-ethylmaleimide-insensitive factors are required for Ca2+-stimulated exocytosis of insulin,” Biochemical Journal, vol. 314, no. 1, pp. 199–203, 1996. View at Google Scholar · View at Scopus
- R. Regazzi, C. B. Wollheim, J. Lang et al., “VAMP-2 and cellubrevin are expressed in pancreatic β-cells and are essential for Ca2+—but not for GTPγS-induced insulin secretion,” EMBO Journal, vol. 14, no. 12, pp. 2723–2730, 1995. View at Google Scholar · View at Scopus
- K. Sadoul, J. Lang, C. Montecucco et al., “SNAP-25 is expressed in islets of Langerhans and is involved in insulin release,” Journal of Cell Biology, vol. 128, no. 6, pp. 1019–1028, 1995. View at Publisher · View at Google Scholar · View at Scopus
- S. N. Yang, O. Larsson, R. Bränström et al., “Syntaxin 1 interacts with the LD subtype of voltage-gated Ca2+ channels in pancreatic β cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 18, pp. 10164–10169, 1999. View at Google Scholar · View at Scopus
- M. N. Wu, J. T. Littleton, M. A. Bhat, A. Prokop, and H. J. Bellen, “ROP, the Drosophila Sec1 homolog, interacts with syntaxin and regulates neurotransmitter release in a dosage-dependent manner,” EMBO Journal, vol. 17, no. 1, pp. 127–139, 1998. View at Publisher · View at Google Scholar · View at Scopus
- S. Orita, A. Naito, G. Sakaguchi et al., “Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent exocytotic machinery,” The Journal of Biological Chemistry, vol. 272, no. 26, pp. 16081–16084, 1997. View at Publisher · View at Google Scholar · View at Scopus
- H. D. Vanguilder, H. Yan, J. A. Farley, W. E. Sonntag, and W. M. Freeman, “Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome,” Journal of Neurochemistry, vol. 113, no. 6, pp. 1577–1588, 2010. View at Publisher · View at Google Scholar · View at Scopus
- K. Maedler, D. M. Schumann, F. Schulthess et al., “Aging correlates with decreased β-cell proliferative capacity and enhanced sensitivity to apoptosis: a potential role for fas and pancreatic duodenal homeobox-1,” Diabetes, vol. 55, no. 9, pp. 2455–2462, 2006. View at Publisher · View at Google Scholar · View at Scopus
- A. E. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, R. A. Rizza, and P. C. Butler, “β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes,” Diabetes, vol. 52, no. 1, pp. 102–110, 2003. View at Publisher · View at Google Scholar · View at Scopus
- K. Maedler, G. A. Spinas, R. Lehmann et al., “Glucose induces β-cell apoptosis via upregulation of the Fas receptor in human islets,” Diabetes, vol. 50, no. 8, pp. 1683–1690, 2001. View at Google Scholar · View at Scopus
- C. Reers, S. Erbel, I. Esposito et al., “Impaired islet turnover in human donor pancreata with aging,” European Journal of Endocrinology, vol. 160, no. 2, pp. 185–191, 2009. View at Publisher · View at Google Scholar · View at Scopus
- Z. Gu, Y. Du, Y. Liu et al., “Effect of aging on islet beta-cell function and its mechanisms in Wistar rats,” Age. In press.
- P. C. Butler, J. Chou, W. B. Carter et al., “Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans,” Diabetes, vol. 39, no. 6, pp. 752–756, 1990. View at Google Scholar · View at Scopus
- P. Westermark, A. Andersson, and G. T. Westermark, “Islet amyloid polypeptide, islet amyloid, and diabetes mellitus,” Physiological Reviews, vol. 91, no. 3, pp. 795–826, 2011. View at Publisher · View at Google Scholar · View at Scopus
- E. Law, S. Lu, T. J. Kieffer et al., “Differences between amyloid toxicity in alpha and beta cells in human and mouse islets and the role of caspase-3,” Diabetologia, vol. 53, no. 7, pp. 1415–1427, 2010. View at Publisher · View at Google Scholar · View at Scopus
- J. Janson, R. H. Ashley, D. Harrison, S. McIntyre, and P. C. Butler, “The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles,” Diabetes, vol. 48, no. 3, pp. 491–498, 1999. View at Google Scholar · View at Scopus
- C. B. Verchere, D. A. D'Alessio, R. D. Palmiter et al., “Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 8, pp. 3492–3496, 1996. View at Publisher · View at Google Scholar · View at Scopus
- A. M. Ackermann and M. Gannon, “Molecular regulation of pancreatic β-cell mass development, maintenance, and expansion,” Journal of Molecular Endocrinology, vol. 38, no. 1-2, pp. 193–206, 2007. View at Publisher · View at Google Scholar · View at Scopus
- J. A. Parsons, T. C. Brelje, and R. L. Sorenson, “Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion,” Endocrinology, vol. 130, no. 3, pp. 1459–1466, 1992. View at Publisher · View at Google Scholar · View at Scopus
- F. Levine and P. Itkin-Ansari, “β-cell regeneration: neogenesis, replication or both?” Journal of Molecular Medicine, vol. 86, no. 3, pp. 247–258, 2008. View at Publisher · View at Google Scholar · View at Scopus
- X. Xu, J. D'Hoker, G. Stangé et al., “β cells can be generated from endogenous progenitors in injured adult mouse pancreas,” Cell, vol. 132, no. 2, pp. 197–207, 2008. View at Publisher · View at Google Scholar · View at Scopus
- N. A. Hanley, K. P. Hanley, P. J. Miettinen, and T. Otonkoski, “Weighing up β-cell mass in mice and humans: self-renewal, progenitors or stem cells?” Molecular and Cellular Endocrinology, vol. 288, no. 1-2, pp. 79–85, 2008. View at Publisher · View at Google Scholar · View at Scopus
- S. I. Tschen, S. Dhawan, T. Gurlo, and A. Bhushan, “Age-dependent decline in β-cell proliferation restricts the capacity of β-cell regeneration in mice,” Diabetes, vol. 58, no. 6, pp. 1312–1320, 2009. View at Publisher · View at Google Scholar · View at Scopus
- M. M. Rankin and J. A. Kushner, “Adaptive β-cell proliferation is severely restricted with advanced age,” Diabetes, vol. 58, no. 6, pp. 1365–1372, 2009. View at Publisher · View at Google Scholar · View at Scopus
- I. K. Park, S. J. Morrison, and M. F. Clarke, “Bmi1, stem cells, and senescence regulation,” Journal of Clinical Investigation, vol. 113, no. 2, pp. 175–179, 2004. View at Publisher · View at Google Scholar · View at Scopus
- S. W. Lowe and C. J. Sherr, “Tumor suppression by Ink4a-Arf: progress and puzzles,” Current Opinion in Genetics and Development, vol. 13, no. 1, pp. 77–83, 2003. View at Publisher · View at Google Scholar · View at Scopus
- S. G. Rane, P. Dubus, R. V. Mettus et al., “Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in β-islet cell hyperplasia,” Nature Genetics, vol. 22, no. 1, pp. 44–54, 1999. View at Publisher · View at Google Scholar · View at Scopus
- I. Cozar-Castellano, M. Weinstock, M. Haught, S. Velázquez-Garcia, D. Sipula, and A. F. Stewart, “Evaluation of β-cell replication in mice transgenic for hepatocyte growth factor and placental lactogen: comprehensive characterization of the G1/S regulatory proteins reveals unique involvement of p21 cip,” Diabetes, vol. 55, no. 1, pp. 70–77, 2006. View at Publisher · View at Google Scholar · View at Scopus
- J. Krishnamurthy, C. Torrice, M. R. Ramsey et al., “Ink4a/Arf expression is a biomarker of aging,” Journal of Clinical Investigation, vol. 114, no. 9, pp. 1299–1307, 2004. View at Publisher · View at Google Scholar · View at Scopus
- N. M. Fiaschi-Taesch, F. Salim, J. Kleinberger et al., “Induction of human β-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6,” Diabetes, vol. 59, no. 8, pp. 1926–1936, 2010. View at Publisher · View at Google Scholar · View at Scopus
- J. Krishnamurthy, M. R. Ramsey, K. L. Ligon et al., “p16INK4a induces an age-dependent decline in islet regenerative potential,” Nature, vol. 443, no. 7110, pp. 453–457, 2006. View at Publisher · View at Google Scholar · View at Scopus
- J. Martín, S. L. Hunt, P. Dubus et al., “Genetic rescue of Cdk4 null mice restores pancreatic β-cell proliferation but not homeostatic cell number,” Oncogene, vol. 22, no. 34, pp. 5261–5269, 2003. View at Publisher · View at Google Scholar · View at Scopus
- J. A. Kushner, M. A. Ciemerych, E. Sicinska et al., “Cyclins D2 and D1 are essential for postnatal pancreatic β-cell growth,” Molecular and Cellular Biology, vol. 25, no. 9, pp. 3752–3762, 2005. View at Publisher · View at Google Scholar · View at Scopus
- U. Eriksson and I. Swenne, “Diabetes in pregnancy: growth of the fetal pancreatic B cells in the rat,” Biology of the Neonate, vol. 42, no. 5-6, pp. 239–248, 1982. View at Google Scholar · View at Scopus
- L. Baeyens, S. De Breuck, J. Lardon, J. K. Mfopou, I. Rooman, and L. Bouwens, “In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells,” Diabetologia, vol. 48, no. 1, pp. 49–57, 2005. View at Publisher · View at Google Scholar · View at Scopus
- B. Blondeau, A. Garofano, P. Czernichow, and B. Bréant, “Age-dependent inability of the endocrine pancreas to adapt to pregnancy: a long-term consequence of perinatal malnutrition in the rat,” Endocrinology, vol. 140, no. 9, pp. 4208–4213, 1999. View at Google Scholar · View at Scopus
- L. Rosenberg, W. P. Duguid, R. A. Brown, and A. I. Vinik, “Induction of nesidioblastosis will reverse diabetes in Syrian golden hamster,” Diabetes, vol. 37, no. 3, pp. 334–341, 1988. View at Google Scholar · View at Scopus
- M. Lipsett, R. Aikin, M. Castellarin et al., “Islet neogenesis: a potential therapeutic tool in type 1 diabetes,” International Journal of Biochemistry and Cell Biology, vol. 38, no. 4, pp. 498–503, 2006. View at Publisher · View at Google Scholar · View at Scopus
- G. L. Pittenger, D. A. Taylor-Fishwick, R. H. Johns, N. Burcus, S. Kosuri, and A. I. Vinik, “Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs,” Pancreas, vol. 34, no. 1, pp. 103–111, 2007. View at Publisher · View at Google Scholar · View at Scopus
- S. C. Hanley, A. Pilotte, B. Massie, and L. Rosenberg, “Cellular origins of adult human islet in vitro dedifferentiation,” Laboratory Investigation, vol. 88, no. 7, pp. 761–772, 2008. View at Publisher · View at Google Scholar · View at Scopus
- R. Rafaeloff, G. L. Pittenger, S. W. Barlow et al., “Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters,” Journal of Clinical Investigation, vol. 99, no. 9, pp. 2100–2109, 1997. View at Google Scholar · View at Scopus
- W. L. Suarez-Pinzon, J. R. Lakey, S. J. Brand, and A. Rabinovitch, “Combination therapy with epidermal growth factor and gastrin induces neogenesis of human islet β-cells from pancreatic duct cells and an increase in functional β-cell mass,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, pp. 3401–3409, 2005. View at Google Scholar
- C. Tourrel, D. Bailbé, M. J. Meile, M. Kergoat, and B. Portha, “Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age,” Diabetes, vol. 50, no. 7, pp. 1562–1570, 2001. View at Google Scholar · View at Scopus
- M. Chen, R. N. Bergman, and D. Porte Jr., “Insulin resistance and beta-cell dysfunction in aging: the importance of dietary carbohydrate,” The Journal of Clinical Endocrinology & Metabolism, vol. 67, pp. 951–957, 1988. View at Google Scholar
- R. A. DeFronzo, “Glucose intolerance and aging,” Diabetes Care, vol. 4, no. 4, pp. 493–501, 1981. View at Google Scholar · View at Scopus
- J. W. Rowe, K. L. Minaker, J. A. Pallotta, and J. S. Flier, “Characterization of the insulin resistance of aging,” Journal of Clinical Investigation, vol. 71, no. 6, pp. 1581–1587, 1983. View at Google Scholar · View at Scopus
- M. I. Harris, W. C. Hadden, W. C. Knowler, and P. H. Bennett, “Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 yr,” Diabetes, vol. 36, no. 4, pp. 523–534, 1987. View at Google Scholar · View at Scopus
- H. Yki-Järvinen, “Role of insulin resistance in the pathogenesis of NIDDM,” Diabetologia, vol. 38, no. 12, pp. 1378–1388, 1995. View at Publisher · View at Google Scholar · View at Scopus
- B. Bryhni, T. G. Jenssen, K. Olafsen, and J. H. Eikrem, “Age or waist as determinant of insulin action?” Metabolism, vol. 52, no. 7, pp. 850–857, 2003. View at Publisher · View at Google Scholar · View at Scopus
- K. J. Catalano, R. N. Bergman, and M. Ader, “Increased susceptibility to insulin resistance associated with abdominal obesity in aging rats,” Obesity Research, vol. 13, no. 1, pp. 11–20, 2005. View at Google Scholar · View at Scopus
- D. B. Carr, K. M. Utzschneider, R. L. Hull et al., “Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome,” Diabetes, vol. 53, no. 8, pp. 2087–2094, 2004. View at Publisher · View at Google Scholar · View at Scopus
- G. Enzi, M. Gasparo, and P. R. Biondetti, “Subcutaneous and visceral fat distribution according to sex, age, and overweight, evaluated by computed tomography,” American Journal of Clinical Nutrition, vol. 44, no. 6, pp. 739–746, 1986. View at Google Scholar · View at Scopus
- G. A. Borkan, D. E. Hults, S. G. Gerzof, and A. H. Robbins, “Comparison of body composition in middle-aged and elderly males using computed tomography,” American Journal of Physical Anthropology, vol. 66, no. 3, pp. 289–295, 1985. View at Google Scholar · View at Scopus
- G. A. Borkan, D. E. Hults, and S. G. Gerzof, “Age changes in body composition revealed by computed tomography,” Journals of Gerontology, vol. 38, no. 6, pp. 673–677, 1983. View at Google Scholar · View at Scopus
- K. Kotani, K. Tokunaga, S. Fujioka et al., “Sexual dimorphism of age-related changes in whole-body fat distribution in the obese,” International Journal of Obesity, vol. 18, no. 4, pp. 207–212, 1994. View at Google Scholar · View at Scopus
- D. Rudman, M. H. Kutner, C. M. Rogers et al., “Impaired growth hormone secretion in the adult population. Relation to age and adiposity,” Journal of Clinical Investigation, vol. 67, no. 5, pp. 1361–1369, 1981. View at Google Scholar · View at Scopus
- P. Bjorntorp, ““Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes,” Arteriosclerosis, vol. 10, no. 4, pp. 493–496, 1990. View at Google Scholar · View at Scopus
- I. Gabriely, X. H. Ma, X. M. Yang et al., “Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?” Diabetes, vol. 51, no. 10, pp. 2951–2958, 2002. View at Google Scholar · View at Scopus
- S. E. Borst, C. F. Conover, and G. J. Bagby, “Association of resistin with visceral fat and muscle insulin resistance,” Cytokine, vol. 32, no. 1, pp. 39–44, 2005. View at Publisher · View at Google Scholar · View at Scopus
- L. K. Heilbronn and E. Ravussin, “Calorie restriction and aging: review of the literature and implications for studies in humans,” American Journal of Clinical Nutrition, vol. 78, no. 3, pp. 361–369, 2003. View at Google Scholar · View at Scopus
- R. Muzumdar, D. B. Allison, D. M. Huffman et al., “Visceral adipose tissue modulates mammalian longevity,” Aging Cell, vol. 7, no. 3, pp. 438–440, 2008. View at Publisher · View at Google Scholar · View at Scopus
- E. E. Kershaw and J. S. Flier, “Adipose tissue as an endocrine organ,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2548–2556, 2004. View at Publisher · View at Google Scholar · View at Scopus
- G. Atzmon, X. M. Yang, R. Muzumdar, X. H. Ma, I. Gabriely, and N. Barzilai, “Differential gene expression between visceral and subcutaneous fat depots,” Hormone and Metabolic Research, vol. 34, no. 11-12, pp. 622–628, 2002. View at Publisher · View at Google Scholar · View at Scopus
- M. Alvehus, J. Buren, M. Sjostrom et al., “The human visceral fat depot has a unique inflammatory profile,” Obesity, vol. 18, pp. 879–883, 2010. View at Google Scholar
- D. M. Huffman and N. Barzilai, “Role of visceral adipose tissue in aging,” Biochimica et Biophysica Acta, vol. 1790, no. 10, pp. 1117–1123, 2009. View at Publisher · View at Google Scholar · View at Scopus
- L. Liu, C. Ji, J. Chen et al., “A global genomic view of MIF knockdown-mediated cell cycle arrest,” Cell Cycle, vol. 7, no. 11, pp. 1678–1692, 2008. View at Google Scholar · View at Scopus
- R. A. Mitchell, H. Liao, J. Chesney et al., “Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 1, pp. 345–350, 2002. View at Publisher · View at Google Scholar · View at Scopus
- J. M. Harper, J. E. Wilkinson, and R. A. Miller, “Macrophage migration inhibitory factor-knockout mice are long lived and respond to caloric restriction,” FASEB Journal, vol. 24, no. 7, pp. 2436–2442, 2010. View at Publisher · View at Google Scholar · View at Scopus
- A. Salminen and K. Kaarniranta, “Control of p53 and NF-κB signaling by WIP1 and MIF: role in cellular senescence and organismal aging,” Cellular Signalling, vol. 23, no. 5, pp. 747–752, 2011. View at Publisher · View at Google Scholar · View at Scopus
- S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante, “Obesity is associated with macrophage accumulation in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003. View at Publisher · View at Google Scholar · View at Scopus
- F. H. Einstein, D. M. Huffman, S. Fishman et al., “Aging per se increases the susceptibility to free fatty acid-induced insulin resistance,” Journals of Gerontology—Series A, vol. 65, no. 8, pp. 800–808, 2010. View at Publisher · View at Google Scholar · View at Scopus
- F. Licastro, G. Candore, D. Lio et al., “Innate immunity and inflammation in ageing: a key for understanding age-related diseases,” Immunity and Ageing, vol. 2, article 8, 2005. View at Publisher · View at Google Scholar · View at Scopus
- G. Boden, F. Jadali, J. White et al., “Effects of fat on insulin-stimulated carbohydrate metabolism in normal men,” Journal of Clinical Investigation, vol. 88, no. 3, pp. 960–966, 1991. View at Google Scholar · View at Scopus
- G. Boden and X. Chen, “Effects of fat on glucose uptake and utilization in patients with non- insulin-dependent diabetes,” Journal of Clinical Investigation, vol. 96, no. 3, pp. 1261–1268, 1995. View at Google Scholar · View at Scopus
- M. Roden, T. B. Price, G. Perseghin et al., “Mechanism of free fatty acid-induced insulin resistance in humans,” Journal of Clinical Investigation, vol. 97, no. 12, pp. 2859–2865, 1996. View at Google Scholar · View at Scopus
- A. T. M. G. Santomauro, G. Boden, M. E. R. Silva et al., “Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects,” Diabetes, vol. 48, no. 9, pp. 1836–1841, 1999. View at Publisher · View at Google Scholar · View at Scopus
- G. Boden, X. Chen, J. Ruiz, J. V. White, and L. Rossetti, “Mechanisms of fatty acid-induced inhibition of glucose uptake,” Journal of Clinical Investigation, vol. 93, no. 6, pp. 2438–2446, 1994. View at Google Scholar · View at Scopus
- A. Dresner, D. Laurent, M. Marcucci et al., “Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity,” Journal of Clinical Investigation, vol. 103, no. 2, pp. 253–259, 1999. View at Google Scholar · View at Scopus
- S. I. Itani, N. B. Ruderman, F. Schmieder, and G. Boden, “Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α,” Diabetes, vol. 51, no. 7, pp. 2005–2011, 2002. View at Google Scholar · View at Scopus
- V. T. Samuel, K. F. Petersen, and G. I. Shulman, “Lipid-induced insulin resistance: unravelling the mechanism,” The Lancet, vol. 375, no. 9733, pp. 2267–2277, 2010. View at Publisher · View at Google Scholar · View at Scopus
- L. Koch, F. T. Wunderlich, J. Seibler et al., “Central insulin action regulates peripheral glucose and fat metabolism in mice,” Journal of Clinical Investigation, vol. 118, no. 6, pp. 2132–2147, 2008. View at Publisher · View at Google Scholar · View at Scopus
- R. W. Gelling, G. J. Morton, C. D. Morrison et al., “Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes,” Cell Metabolism, vol. 3, no. 1, pp. 67–73, 2006. View at Publisher · View at Google Scholar · View at Scopus
- J. Zemva and M. Schubert, “Central insulin and insulin-like growth factor-1 signaling: implications for diabetes associated dementia,” Current Diabetes Reviews, vol. 7, pp. 356–366, 2011. View at Google Scholar
- E. Steen, B. M. Terry, E. J. Rivera et al., “Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease—is this type 3 diabetes?” Journal of Alzheimer's Disease, vol. 7, no. 1, pp. 63–80, 2005. View at Google Scholar · View at Scopus
- S. Craft, J. Newcomer, S. Kanne et al., “Memory improvement following induced hyperinsulinemia in Alzheimer's disease,” Neurobiology of Aging, vol. 17, no. 1, pp. 123–130, 1996. View at Publisher · View at Google Scholar · View at Scopus
- S. Craft, S. Asthana, J. W. Newcomer et al., “Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose,” Archives of General Psychiatry, vol. 56, no. 12, pp. 1135–1140, 1999. View at Google Scholar · View at Scopus
- M. A. Reger, G. S. Watson, P. S. Green et al., “Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults,” Journal of Alzheimer's Disease, vol. 13, no. 3, pp. 323–331, 2008. View at Google Scholar · View at Scopus
- S. Craft, L. D. Baker, T. J. Montine et al., “Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial,” Archives of Neurology, vol. 69, pp. 29–38, 2012. View at Google Scholar
- M. L. D. L. A. Fernandes, M. J. A. Saad, and L. A. Velloso, “Effects of age on elements of insulin-signaling pathway in central nervous system of rats,” Endocrine, vol. 16, no. 3, pp. 227–234, 2001. View at Publisher · View at Google Scholar · View at Scopus
- M. Garcia-San Frutos, T. Fernandez-Agullo, and A. J. De Solis, “Impaired central insulin response in aged Wistar rats: role of adiposity,” Endocrinology, vol. 148, pp. 5238–5247, 2007. View at Google Scholar
- D. Porte Jr., D. G. Baskin, and M. W. Schwartz, “Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans,” Diabetes, vol. 54, no. 5, pp. 1264–1276, 2005. View at Publisher · View at Google Scholar · View at Scopus
- D. A. Sandoval, S. Obici, and R. J. Seeley, “Targeting the CNS to treat type 2 diabetes,” Nature Reviews Drug Discovery, vol. 8, no. 5, pp. 386–398, 2009. View at Publisher · View at Google Scholar · View at Scopus
- A. L. McCall, “Diabetes mellitus and the central nervous system,” International Review of Neurobiology, vol. 51, pp. 415–453, 2002. View at Google Scholar · View at Scopus
- H. Li, M. Matheny, M. Nicolson, N. Tümer, and P. J. Scarpace, “Leptin gene expression increases with age independent of increasing adiposity in rats,” Diabetes, vol. 46, no. 12, pp. 2035–2039, 1997. View at Google Scholar · View at Scopus
- M. A. Banerji, N. Faridi, R. Atluri et al., “Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men,” The Journal of Clinical Endocrinology & Metabolism, vol. 84, pp. 137–144, 1999. View at Google Scholar
- Z. W. Wang, W. T. Pan, Y. Lee, T. Kakuma, Y. T. Zhou, and R. H. Unger, “The role of leptin resistance in the lipid abnormalities of aging,” FASEB Journal, vol. 15, no. 1, pp. 108–114, 2001. View at Publisher · View at Google Scholar · View at Scopus
- D. L. Eizirik, A. K. Cardozo, and M. Cnop, “The role for endoplasmic reticulum stress in diabetes mellitus,” Endocrine Reviews, vol. 29, no. 1, pp. 42–61, 2008. View at Publisher · View at Google Scholar · View at Scopus
- S. G. Hussain and K. V. Ramaiah, “Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging,” Biochemical and Biophysical Research Communications, vol. 355, pp. 365–370, 2007. View at Google Scholar
- N. Naidoo, “ER and aging-protein folding and the ER stress response,” Ageing Research Reviews, vol. 8, no. 3, pp. 150–159, 2009. View at Publisher · View at Google Scholar · View at Scopus
- R. Kerkela, L. Kockeritz, K. MacAulay et al., “Deletion of GSK-3β in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation,” Journal of Clinical Investigation, vol. 118, no. 11, pp. 3609–3618, 2008. View at Publisher · View at Google Scholar · View at Scopus
- P. J. Coon, E. M. Rogus, D. Drinkwater et al., “Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age,” The Journal of Clinical Endocrinology & Metabolism, vol. 75, pp. 1125–1132, 1992. View at Google Scholar
- G. S. Meneilly, K. L. Minaker, D. Elahi, and J. W. Rowe, “Insulin action in aging man: evidence for tissue-specific differences at low physiologic insulin levels,” Journals of Gerontology, vol. 42, no. 2, pp. 196–201, 1987. View at Google Scholar · View at Scopus
- A. Natali, E. Toschi, S. Camastra et al., “Determinants of postabsorptive endogenous glucose output in non-diabetic subjects. European Group for the Study of Insulin Resistance (EGIR),” Diabetologia, vol. 43, pp. 1266–1272, 2000. View at Google Scholar
- G. S. Meneilly, T. Elliott, D. Tessier, L. Hards, and H. Tildesley, “NIDDM in the elderly,” Diabetes Care, vol. 19, no. 12, pp. 1320–1325, 1996. View at Google Scholar · View at Scopus
- A. J. Scheen, “Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion?” Diabetes and Metabolism, vol. 31, no. 2, pp. 5–27, 2005. View at Google Scholar · View at Scopus
- J. A. Houmard, M. D. Weidner, P. L. Dolan et al., “Skeletal muscle GLUT4 protein concentration and aging in humans,” Diabetes, vol. 44, no. 5, pp. 555–560, 1995. View at Google Scholar · View at Scopus
- E. Ferrannini, S. Vichi, H. Beck-Nielsen et al., “Insulin action and age. European Group for the Study of Insulin Resistance (EGIR),” Diabetes, vol. 45, pp. 947–953, 1996. View at Google Scholar
- C. L. Rice, D. A. Cunningham, D. H. Paterson, and M. S. Lefcoe, “Arm and leg composition determined by computed tomography in young and elderly men,” Clinical Physiology, vol. 9, no. 3, pp. 207–220, 1989. View at Google Scholar · View at Scopus