Diabetes, the Brain, and Cognition

Scientists once thought the brain played little part in diabetes—a disease in which the body is unable to produce or use the hormone insulin from the pancreas. Now, new research indicates that the brain has its own insulin receptors and plays a big role in normal blood sugar control. Scientists are only beginning to understand the details of the brain’s role in normal insulin and glucose control, diabetes, and the cognitive deficits associated with the disease. Better treatments for people with diabetes are sure to follow.

Prick my finger, again. My blood sugar is too high, too low. Inject insulin, again. Will I be one of the many at risk for Alzheimer’s disease? Will I gain more weight? These are just some of the worries that people with diabetes face on a daily basis. But thankfully, new brain research may soon benefit people with this chronic disease.

Scientists once thought the brain played little part in diabetes—a disease in which the body is unable to produce or use insulin from the pancreas, the organ that produces it. It was long believed that insulin was made exclusively by the pancreas and that the hormone’s effects were limited to the body’s peripheral tissues. These tissues respond to insulin by letting in blood sugar, or glucose—energy for the body’s cells.

Now, new studies indicate that the brain has its own insulin receptors—proteins located on the surface of brain cells—and play a big role in normal glucose control.

Diabetes can damage many parts of the body, leading to loss of vision and sensation, strokes, and heart disease. Nearly 73,000 Americans die from diabetes annually, making it one of the top disease killers. Diabetes also is associated with impaired cognitive function and increased risk for dementia, including Alzheimer’s disease.

Advanced knowledge of how the brain is involved in normal insulin and glucose control, and in diabetes, could lead to:

• Better understanding of the two types of diabetes: Type I and the more common Type II, which accounts for almost 95 percent of all diabetes cases in North America.
• Enhanced treatments for diabetes—even obesity and other metabolic disorders.

New research is helping to uncover the link between diabetes and Alzheimer’s disease. When diabetes strikes and insulin’s signal is ignored by cells, the brain may not get the large amount of glucose energy it needs, especially for memory. Loss of brain cells and memory function may result, especially in the hippocampus—a brain region involved in learning and memory. Increased insulin concentrations also appear to boost levels of beta-amyloid—a protein involved in the formation of senile plaques that can lead to Alzheimer’s.

Scientists are only beginning to understand how general cognitive deficits occur, but new studies are providing some clues.

Insulin and related growth proteins in the brain are vital for cell survival, and both glucose and insulin appear to regulate many brain functions, including learning and memory. Dysfunction of these chemicals contributes to cognitive deficits. Chronic episodes of high or low levels of blood glucose may directly affect insulin’s actions in the brain or damage brain cells, leading to cognitive impairments. Diabetes may be wreaking havoc especially in the hippocampus. The hypothalamus—a brain region that regulates metabolic processes and activities like hunger, thirst, and body temperature—also appears to be involved, especially areas that respond to low blood sugar and regulate energy balance, body weight, and the sensitivity of the liver and muscles to insulin.

Current treatments for diabetes involve a healthful diet and exercise, pills that control glucose levels, or frequent injections of insulin, often accompanied by unwanted side effects, such as weight gain. But studying the role that the brain plays in diabetes and its treatment is giving hope for more effective medications.

Recently, scientists improved rats’ reaction to insulin therapy twofold—thus reducing the need for insulin. By enhancing brain cell signaling involved in normal insulin response in the hypothalamus, scientists heightened insulin’s ability to lower blood sugar in the treatment of diabetes.

In another study, researchers reduced the incidence of diabetes in mice by 80 percent by removing pain nerves that innervate the pancreas. Scientists discovered that these nerves played a role in regulating blood sugar control and were functioning abnormally in animal models of diabetes. Researchers also reversed diabetes by injecting the pancreas with a small protein secreted by these pain nerves.

Better and more efficient treatments will help combat diabetes and also decrease unwanted side effects. Research into the brain’s role in diabetes and its treatment may be the key to helping people with diabetes worry about one less thing.

For additional information, check out:

J Alzheimer's Dis. 2005 Feb;7(1):63-80. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease - is this type 3 diabetes? Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM.

Psychology Today. May-June 2005. New form of diabetes may damage the brain. Tan K.

Cell Metabolism. Jan2006;3(1): 67–73. Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Gelling RW, Morton GJ, Morrison CD, Niswender KD, Myers MG Jr, Rhodes CJ, Schwartz MW.

The Harvard Mahoney Neuroscience Institute Letter: On the Brain. Fall 1994;3(4). A common mechanism in Alzheimer’s and Adult-onselt diabetes. Yanker, BA.

Eur. J. Pharmacol. 2004;490:169–175. The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations. Allen KV, Frier BM, Strachan MW.

Lancet Neurol. 2006;5:64–74. Risk of dementia in diabetes mellitus: a systematic review. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P.

Arch. Gen. Psychiatry. 1999;56:1135-1140. Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Craft S, Asthana S, Newcomer JW, Wilkinson CW, Matos IT, Baker LD, Cherrier M, Lofgreen C, Latendresse S, Petrova A, Plymate S, Raskind M, Grimwood K, Veith RC.

Neurology. 1998;50:164-168. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr.

Science. 2003 July 4;301(5629):40-41. Insulin insults may spur Alzheimer’s disease. Taubes, G.

Diabetes Care. 2006 Nov;29(11):2539-2548. Brain imaging in patients with diabetes: a systematic review. van Harten B, de Leeuw FE, Weinstein HC, Scheltens P, Biessels GJ.

Diabetes. 2006 Feb;55(2):326-333. Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry. Musen G, Lyoo IK, Sparks CR, Weinger K, Hwang J, Ryan CM, Jimerson DC, Hennen J, Renshaw PF, Jacobson AM.

Science. 1998 April 24;280(5363):517-519. Tracking insulin to the mind. Wickelgren I.

Am. J. Clin. Nutr. 1998 Apr. 67(4):764S-771S. Glucose, memory, and aging. Korol DL, Gold PE.

Dosch, HM, et al. TRPV1+ Sensory Neurons Control ß Cell Stress and Islet Inflammation in Autoimmune Diabetes. Cell. Dec15, 2007;127(6):1123-1135.

Voltarelli, JC, et al. Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus. JAMA. 2007;297:1568-1576.

van Harten, et al. Brain Imaging in Patients with Diabetes. ADA: Diabetes Care 2006;29:2539-2548.

Biessels GJ, et al. Ageing and diabetes: implications for brain function. Eur. J. Pharmacol. 2002;441:1–14.