Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?

Abstract

Ever since Claude Bernards discovery in the mid 19th-century that a lesion in the floor of the third ventricle in dogs led to altered systemic glucose levels, a role of the CNS in whole-body glucose regulation has been acknowledged. However, this finding was later overshadowed by the isolation of pancreatic hormones in the 20th century. Since then, the understanding of glucose homeostasis and pathology has primarily evolved around peripheral mechanism. Due to scientific advances over these last few decades, however, increasing attention has been given to the possibility of the brain as a key player in glucose regulation and the pathogenesis of metabolic disorders such as type 2 diabetes. Studies of animals have enabled detailed neuroanatomical mapping of CNS structures involved in glucose regulation and key neuronal circuits and intracellular pathways have been identified. Furthermore, the development of neuroimaging techniques has provided methods to measure changes of activity in specific CNS regions upon diverse metabolic challenges in humans. In this narrative review, we discuss the available evidence on the topic. We conclude that there is much evidence in favor of active CNS involvement in glucose homeostasis but the relative importance of central vs. peripheral mechanisms remains to be elucidated. An increased understanding of this field may lead to new CNS-focusing pharmacologic strategies in the treatment of type 2 diabetes.

Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review

“…Brain metabolism accounts for 50% of total body glucose as its main energy source having neurons with the highest energy demand (1)(2)(3). Neuronal energetic dyshomeostasis is behind the onset of numerous devastating pathologic nervous conditions, characterized by reduced neuronal survival and an overall deterioration of cognitive abilities (4).…”

Altered hormonal and autonomic nerve responses to hypo- and hyperglycaemia are found in overweight and insulin-resistant individuals and may contribute to the development of type 2 diabetes

“…Hypoglycaemia elicits a typical response consisting of secretion of counter-regulatory hormones (glucagon, cortisol, catecholamines and growth hormone) and activation of the autonomic nervous system (ANS), which collectively act to raise glucose levels [2,3]. Dysregulation in some of these hormonal and neural systems has been demonstrated in type 2 diabetes, prediabetes and obesity, suggesting a possible role in the development of type 2 diabetes [4][5][6][7][8][9][10].…”

“…A biphasic glucagon response to different glucose levels has been described in mouse islets in vitro, with increased secretion in hyperglycaemic as well as hypoglycaemic conditions [ 15 ] but there is no evidence of this phenomena in human islets to our knowledge. The response of cortisol, adrenocorticotropic hormone (ACTH) and catecholamines to hypoglycaemia is reportedly, albeit inconsistently, augmented in obesity and/or type 2 diabetes, whereas basal levels have not been significantly different compared with healthy controls [ 7 – 10 , 16 , 17 ]. The growth hormone response to hypoglycaemia, on the other hand, has been consistently shown to be attenuated in obese individuals [ 18 , 19 ].…”

No Effects of Acute Psychosocial Stress on Working Memory in Older People With Type 2 Diabetes

“…Consequently, large amounts of alpha-amylase (an indirect marker of SNS) and cortisol (C), the main human glucocorticoid, are secreted. The chronic activation of these two systems produces an increase in BG levels, contributing to T2D development ( Boaz et al, 2013 ; Lundqvist et al, 2019 ).…”