Role of Insulin in Cognitive Functions of the Central Nervous System

Document Type : Review Article

Authors

1 Student, Department of Physiology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Biosensor Research Center AND Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

It was previously believed that insulin only has environmental performance and is not capable of crossing the blood-brain barrier or affecting the central nervous system. However, it is now clear that insulin and its receptors are present in the central nervous system. This hormone not only passes the blood-brain barrier, but may also be synthesized by neurons in the brain. As a neuropeptide, insulin is involved in the development and function of the nervous system. Deficiency of this hormone or dysfunction of its central receptors causes serious damage to cognitive processes including learning and memory. Such effects might be due to the non-metabolic effects of insulin. This study reviewed the role of insulin in neuronal processes.

Keywords

References

  1. Kahn CR. The molecular mechanism of insulin action. Annu Rev Med 1985; 36: 429-51.
  2. Laron Z. Insulin and the brain. Arch Physiol Biochem 2009; 115(2): 112-6.
  3. Debons AF, Krimsky I, From A. A direct action of insulin on the hypothalamic satiety center. Am J Physiol 1970; 219(4): 938-43.
  4. Reisi P, Alaei H, Babri S, Sharifi MR, Mohaddes G. Effects of treadmill running on spatial learning and memory in streptozotocin-induced diabetic rats. Neurosci Lett 2009; 455(2): 79-83.
  5. Reisi P, Babri S, Alaei H, Sharifi MR, Mohaddes G, Lashgari R. Effects of treadmill running on short-term pre-synaptic plasticity at dentate gyrus of streptozotocin-induced diabetic rats. Brain Res 2008; 1211: 30-6.
  6. Hoybergs YM, Meert TF. The effect of low-dose insulin on mechanical sensitivity and allodynia in type I diabetes neuropathy. Neurosci Lett 2007; 417(2): 149-54.
  7. Dobretsov M, Romanovsky D, Stimers JR. Early diabetic neuropathy: triggers and mechanisms. World J Gastroenterol 2007; 13(2): 175-91.
  8. Bloomgarden ZT. Diabetic neuropathy. Diabetes Care 2007; 30(4): 1027-32.
  9. Reisi P, Babri S, Alaei H, Sharifi MR, Mohaddes G, Noorbakhsh SM, et al. Treadmill running improves long-term potentiation (LTP) defects in streptozotocin-induced diabetes at dentate gyrus in rats. Pathophysiology 2010; 17(1): 33-8.
  10. Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gispen WH. Cerebral function in diabetes mellitus. Diabetologia 1994; 37(7): 643-50.
  11. Gispen WH, Biessels GJ. Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 2000; 23(11): 542-9.
  12. Araki Y, Nomura M, Tanaka H, Yamamoto H, Yamamoto T, Tsukaguchi I, et al. MRI of the brain in diabetes mellitus. Neuroradiology 1994; 36(2): 101-3.
  13. Di MU, Morano S, Valle E, Pozzessere G. Electrophysiological alterations of the central nervous system in diabetes mellitus. Diabetes Metab Rev 1995; 11(3): 259-77.
  14. Ryan CM. Neurobehavioral complications of type I diabetes. Examination of possible risk factors. Diabetes Care 1988; 11(1): 86-93.
  15. Strachan MW, Deary IJ, Ewing FM, Frier BM. Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care 1997; 20(3): 438-45.
  16. Liang XC, Guo SS, Hagino N. Current status of clinical and experimental researches on cognitive impairment in diabetes. Chin J Integr Med 2006; 12(1): 68-74.
  17. Malone JI, Hanna S, Saporta S, Mervis RF, Park CR, Chong L, et al. Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory. Pediatr Diabetes 2008; 9(6): 531-9.
  18. Gold AE, Deary IJ, Jones RW, O'Hare JP, Reckless JP, Frier BM. Severe deterioration in cognitive function and personality in five patients with long-standing diabetes: a complication of diabetes or a consequence of treatment? Diabet Med 1994; 11(5): 499-505.
  19. McEwen BS, Magarinos AM, Reagan LP. Studies of hormone action in the hippocampal formation: possible relevance to depression and diabetes. J Psychosom Res 2002; 53(4): 883-90.
  20. Beauquis J, Homo-Delarche F, Revsin Y, De Nicola AF, Saravia F. Brain alterations in autoimmune and pharmacological models of diabetes mellitus: focus on hypothalamic-pituitary-adrenocortical axis disturbances. Neuroimmunomodulation 2008; 15(1): 61-7.
  21. Schechter R, Sadiq HF, Devaskar SU. Insulin and insulin mRNA are detected in neuronal cell cultures maintained in an insulin-free/serum-free medium. J Histochem Cytochem 1990; 38(6): 829-36.
  22. Young WS, III. Periventricular hypothalamic cells in the rat brain contain insulin mRNA. Neuropeptides 1986; 8(2): 93-7.
  23. Banks WA. The source of cerebral insulin. Eur J Pharmacol 2004; 490(1-3): 5-12.
  24. Woods SC, Seeley RJ, Baskin DG, Schwartz MW. Insulin and the blood-brain barrier. Curr Pharm Des 2003; 9(10): 795-800.
  25. Zhao WQ, Chen H, Quon MJ, Alkon DL. Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 2004; 490(1-3): 71-81.
  26. Sharifi MR, Alaei H, Reisi P. The Effect of insulin on electrical activity of the brain in rat. J Isfahan Med sch 2005; 23(79): 56-62.
  27. Baura GD, Foster DM, Porte D, Jr., Kahn SE, Bergman RN, Cobelli C, et al. Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain. J Clin Invest 1993; 92(4): 1824-30.
  28. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001; 414(6865): 799-806.
  29. Banks WA, Kastin AJ. Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin. Peptides 1998; 19(5): 883-9.
  30. Wallum BJ, Taborsky GJ, Jr., Porte D, Jr., Figlewicz DP, Jacobson L, Beard JC, et al. Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab 1987; 64(1): 190-4.
  31. Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH. Ageing and diabetes: implications for brain function. Eur J Pharmacol 2002; 441(1-2): 1-14.
  32. Freychet P. Insulin receptors and insulin actions in the nervous system. Diabetes Metab Res Rev 2000; 16(6): 390-2.
  33. Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature 1978; 272(5656): 827-9.
  34. Takahashi M, Yamada T, Tooyama I, Moroo I, Kimura H, Yamamoto T, et al. Insulin receptor mRNA in the substantia nigra in Parkinson's disease. Neurosci Lett 1996; 204(3): 201-4.
  35. Marks JL, Porte D, Jr., Stahl WL, Baskin DG. Localization of insulin receptor mRNA in rat brain by in situ hybridization. Endocrinology 1990; 127(6): 3234-6.
  36. Unger JW, Betz M. Insulin receptors and signal transduction proteins in the hypothalamo-hypophyseal system: a review on morphological findings and functional implications. Histol Histopathol 1998; 13(4): 1215-24.
  37. Baskin DG, Sipols AJ, Schwartz MW, White MF. Immunocytochemical detection of insulin receptor substrate-1 (IRS-1) in rat brain: colocalization with phosphotyrosine. Regul Pept 1993; 48(1-2): 257-66.
  38. Unger J, McNeill TH, Moxley RT, III, White M, Moss A, Livingston JN. Distribution of insulin receptor-like immunoreactivity in the rat forebrain. Neuroscience 1989; 31(1): 143-57.
  39. Adamo M, Raizada MK, LeRoith D. Insulin and insulin-like growth factor receptors in the nervous system. Mol Neurobiol 1989; 3(1-2): 71-100.
  40. Heidenreich KA, Brandenburg D. Oligosaccharide heterogeneity of insulin receptors. Comparison of N-linked glycosylation of insulin receptors in adipocytes and brain. Endocrinology 1986; 118(5): 1835-42.
  41. Baskin DG, Porte D, Jr., Guest K, Dorsa DM. Regional concentrations of insulin in the rat brain. Endocrinology 1983; 112(3): 898-903.
  42. Koch L, Wunderlich FT, Seibler J, Konner AC, Hampel B, Irlenbusch S, et al. Central insulin action regulates peripheral glucose and fat metabolism in mice. J Clin Invest 2008; 118(6): 2132-47.
  43. Konner AC, Hess S, Tovar S, Mesaros A, Sanchez-Lasheras C, Evers N, et al. Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis. Cell Metab 2011; 13(6): 720-8.
  44. O'Brien RM, Granner DK. Regulation of gene expression by insulin. Physiol Rev 1996; 76(4): 1109-61.
  45. Bessman SP, Mohan C. Insulin as a probe of mitochondrial metabolism in situ. Mol Cell Biochem 1997; 174(1-2): 91-6.
  46. Dehghani Dolatabadi HR, Reisi P, Alaei H, Azizi MH, Pilehvarian AA. Folic Acid and coenzyme q10 ameliorate cognitive dysfunction in the rats with intracerebroventricular injection of streptozotocin. Iran J Basic Med Sci 2012; 15(2): 719-24.
  47. Gasparini L, Xu H. Potential roles of insulin and IGF-1 in Alzheimer's disease. Trends Neurosci 2003; 26(8): 404-6.
  48. Boyd FT, Jr., 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(29): 15880-4.
  49. Boyd FT, Jr., Raizada MK. Effects of insulin and tunicamycin on neuronal insulin receptors in culture. Am J Physiol 1983; 245(3): C283-C287.
  50. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D, Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998; 50(1): 164-8.
  51. Abbott MA, Wells DG, Fallon JR. The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosci 1999; 19(17): 7300-8.
  52. Unger JW, Livingston JN, Moss AM. Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog Neurobiol 1991; 36(5): 343-62.
  53. Yamato T, Misumi Y, Yamasaki S, Kino M, Aomine M. Diabetes mellitus decreases hippocampal release of neurotransmitters: an in vivo microdialysis study of awake, freely moving rats. Diabetes Nutr Metab 2004; 17(3): 128-36.
  54. Magarinos AM, Verdugo JM, McEwen BS. Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci U S A 1997; 94(25): 14002-8.
  55. Magarinos AM, McEwen BS. Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci U S A 2000; 97(20): 11056-61.
  56. Gardoni F, Kamal A, Bellone C, Biessels GJ, Ramakers GM, Cattabeni F, et al. Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats. J Neurochem 2002; 80(3): 438-47.
  57. Jahagirdar V, McNay EC. Thyroid hormone's role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes. Metab Brain Dis 2012; 27(2): 101-11.
  58. Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D, et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A 2004; 101(9): 3100-5.
  59. Taylor SI, Accili D, Haft CR, Hone J, Imai Y, Levy-Toledano R, et al. Mechanisms of hormone resistance: lessons from insulin-resistant patients. Acta Paediatr Suppl 1994; 399: 95-104.
  60. Lazarus R, Prettyman R, Cherryman G. White matter lesions on magnetic resonance imaging and their relationship with vascular risk factors in memory clinic attenders. Int J Geriatr Psychiatry 2005; 20(3): 274-9.
  61. Nistico R, Cavallucci V, Piccinin S, Macri S, Pignatelli M, Mehdawy B, et al. Insulin receptor beta-subunit haploinsufficiency impairs hippocampal late-phase LTP and recognition memory. Neuromolecular Med 2012; 14(4): 262-9.
  62. Grillo CA, Piroli GG, Hendry RM, Reagan LP. Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent. Brain Res 2009; 1296: 35-45.
  63. Kopf SR, Baratti CM. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism. Behav Neural Biol 1994; 62(3): 237-43.
  64. Parkes M, White KG. Glucose attenuation of memory impairments. Behav Neurosci 2000; 114(2): 307-19.
  65. Park CR, Seeley RJ, Craft S, Woods SC. Intracerebroventricular insulin enhances memory in a passive-avoidance task. Physiol Behav 2000; 68(4): 509-14.
  66. Park CR. Cognitive effects of insulin in the central nervous system. Neurosci Biobehav Rev 2001; 25(4): 311-23.
  67. Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 2004; 3(3): 169-78.
  68. Smith MA, Sayre LM, Monnier VM, Perry G. Radical AGEing in Alzheimer's disease. Trends Neurosci 1995; 18(4): 172-6.
  69. Lee CC, Huang CC, Wu MY, Hsu KS. Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway. J Biol Chem 2005; 280(18): 18543-50.
  70. Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM. A role for adult neurogenesis in spatial long-term memory. Neuroscience 2005; 130(4): 843-52.
  71. Sweatt JD. Toward a molecular explanation for long-term potentiation. Learn Mem 1999; 6(5): 399-416.
  72. Lynch MA. Long-term potentiation and memory. Physiol Rev 2004; 84(1): 87-136.
  73. Craft S, Asthana S, Cook DG, Baker LD, Cherrier M, Purganan K, et al. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 2003; 28(6): 809-22.
  74. Caccamo A, Oddo S, Sugarman MC, Akbari Y, LaFerla FM. Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol Aging 2005; 26(5): 645-54.
  75. Bernstein HG, Schwarzberg H, Reiser M, Gunther O, Dorn A. Intracerebroventricular infusion of insulin alters the behavior of rats not related to food intake. Endocrinol Exp 1986; 20(4): 387-92.
  76. Benedict C, Hallschmid M, Schultes B, Born J, Kern W. Intranasal insulin to improve memory function in humans. Neuroendocrinology 2007; 86(2): 136-42.
  77. Benedict C, Kern W, Schultes B, Born J, Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab 2008; 93(4): 1339-44.
  78. 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(4): 270-80.
  79. Hallschmid M, Benedict C, Schultes B, Born J, Kern W. Obese men respond to cognitive but not to catabolic brain insulin signaling. Int J Obes (Lond) 2008; 32(2): 275-82.
  80. Maret W. Zinc and diabetes. BioMetals 2005; 18(4): 293-4.
  81. Robertson RP. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 2004; 279(41): 42351-4.
  82. Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res 2012; 2012: 384017.
  83. Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev 2008; 29(4): 494-511.
  84. Reagan LP. Insulin signaling effects on memory and mood. Curr Opin Pharmacol 2007; 7(6): 633-7.
  85. Miles WR, Root HF. Psychologic tests applied to diabetic patients. Arch Intern Med 1922: 30(6): 767–77.
  86. Biessels GJ, Bravenboer B, Gispen WH. Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease: a preface. Eur J Pharmacol 2004; 490(1-3): 1-4.
  87. Jiang LY, Tang SS, Wang XY, Liu LP, Long Y, Hu M, et al. PPARgamma agonist pioglitazone reverses memory impairment and biochemical changes in a mouse model of type 2 diabetes mellitus. CNS Neurosci Ther 2012; 18(8): 659-66.
  88. Messier C, Gagnon M. Glucose regulation and cognitive functions: relation to Alzheimer's disease and diabetes. Behav Brain Res 1996; 75(1-2): 1-11.
  89. Selvarajah D, Wilkinson ID, Davies J, Gandhi R, Tesfaye S. Central nervous system involvement in diabetic neuropathy. Curr Diab Rep 2011; 11(4): 310-22.
  90. Brundel M, van den Berg E, Reijmer YD, de BJ, Kappelle LJ, Biessels GJ. Cerebral haemodynamics, cognition and brain volumes in patients with type 2 diabetes. J Diabetes Complications 2012; 26(3): 205-9.
  91. Reijmer YD, van den Berg E, de BJ, Kessels RP, Kappelle LJ, Algra A, et al. Accelerated cognitive decline in patients with type 2 diabetes: MRI correlates and risk factors. Diabetes Metab Res Rev 2011; 27(2): 195-202.
  92. Ryan CM, Williams TM, Finegold DN, Orchard TJ. Cognitive dysfunction in adults with type 1 (insulin-dependent) diabetes mellitus of long duration: effects of recurrent hypoglycaemia and other chronic complications. Diabetologia 1993; 36(4): 329-34.
  93. Wessels AM, Rombouts SA, Remijnse PL, Boom Y, Scheltens P, Barkhof F, et al. Cognitive performance in type 1 diabetes patients is associated with cerebral white matter volume. Diabetologia 2007; 50(8): 1763-9.
  94. Weinger K, Jacobson AM, Musen G, Lyoo IK, Ryan CM, Jimerson DC, et al. The effects of type 1 diabetes on cerebral white matter. Diabetologia 2008; 51(3): 417-25.
  95. Northam EA, Anderson PJ, Jacobs R, Hughes M, Warne GL, Werther GA. Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset. Diabetes Care 2001; 24(9): 1541-6.
  96. Brands AM, Biessels GJ, de Haan EH, Kappelle LJ, Kessels RP. The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care 2005; 28(3): 726-35.
  97. Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care 2006; 29(8): 1794-9.
  98. Reaven GM, Thompson LW, Nahum D, Haskins E. Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care 1990; 13(1): 16-21.
  99. Fontbonne A, Berr C, Ducimetiere P, Alperovitch A. Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 2001; 24(2): 366-70.
  100. Messier C. Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging. Neurobiol Aging 2005; 26 (Suppl 1): 26-30.
  101. Perlmuter LC, Hakami MK, Hodgson-Harrington C, Ginsberg J, Katz J, Singer DE, et al. Decreased cognitive function in aging non-insulin-dependent diabetic patients. Am J Med 1984; 77(6): 1043-8.
  102. Tojo C, Takao T, Nishioka T, Numata Y, Suemaru S, Hashimoto K. Hypothalamic-pituitary-adrenal axis in WBN/Kob rats with non-insulin dependent diabetes mellitus. Endocr J 1996; 43(2): 233-9.
  103. Lee ZS, Chan JC, Yeung VT, Chow CC, Lau MS, Ko GT, et al. Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients. Diabetes Care 1999; 22(9): 1450-7.
  104. Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer's disease. Eur J Pharmacol 2004; 490(1-3): 97-113.
  105. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 2004; 61(5): 661-6.
  106. MacKnight C, Rockwood K, Awalt E, McDowell I. Diabetes mellitus and the risk of dementia, Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord 2002; 14(2): 77-83.
  107. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (author's transl). Diabete Metab 1977; 3(2): 97-107. [In French].
  108. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329(14): 977-86.
  109. Ferguson SC, Blane A, Wardlaw J, Frier BM, Perros P, McCrimmon RJ, et al. Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function. Diabetes Care 2005; 28(6): 1431-7.
  110. Peila R, Rodriguez BL, Launer LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes 2002; 51(4): 1256-62.
  111. Suzuki M, Sasabe J, Furuya S, Mita M, Hamase K, Aiso S. Type 1 diabetes mellitus in mice increases hippocampal D-serine in the acute phase after streptozotocin injection. Brain Res 2012; 1466: 167-76.
  112. Stolk RP, Breteler MM, Ott A, Pols HA, Lamberts SW, Grobbee DE, et al. Insulin and cognitive function in an elderly population. The Rotterdam Study. Diabetes Care 1997; 20(5): 792-5.
  113. Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 2004; 490(1-3): 115-25.
  114. Craft S. Insulin resistance and cognitive impairment: a view through the prism of epidemiology. Arch Neurol 2005; 62(7): 1043-4.
  115. Lester-Coll N, Rivera EJ, Soscia SJ, Doiron K, Wands JR, de la Monte SM. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. J Alzheimers Dis 2006; 9(1): 13-33.
  116. Schioth HB, Frey WH, Brooks SJ, Benedict C. Insulin to treat Alzheimer's disease: just follow your nose? Expert Rev Clin Pharmacol 2012; 5(1): 17-20.
  117. Ott V, Benedict C, Schultes B, Born J, Hallschmid M. Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism. Diabetes Obes Metab 2012; 14(3): 214-21.
  118. Han X, Ma Y, Liu X, Wang L, Qi S, Zhang Q, et al. Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model. J Neural Transm 2012; 119(11): 1407-16.
  119. Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol 2007; 64(4): 570-5.
  120. Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 2001; 154(7): 635-41.
  121. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis 2005; 7(1): 63-80.
  122. de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2008; 2(6): 1101-13.
  123. Craft S, Asthana S, Newcomer JW, Wilkinson CW, Matos IT, Baker LD, et al. Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Arch Gen Psychiatry 1999; 56(12): 1135-40.
Journal of Isfahan Medical School
Volume 31, Issue 227 - Serial Number 227
January and February 2013
Pages 224-236

Files

History

  • Receive Date: 22 October 2012
  • Revise Date: 02 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics