Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia

Abstract

SUMMARYRecent evidence suggests a key role for the brain in the control of energy metabolism, body fat content and glucose metabolism. Neuronal systems, which regulate energy intake, energy expenditure, and endogenous glucose production, sense and respond to input from hormonal and nutrient-related signals that convey information regarding both body energy stores and current energy availability. In response to this input, adaptive changes occur that promote energy homeostasis and the maintenance of blood glucose levels in the normal range. Defects in this control system are implicated in the link between obesity and type 2 diabetes mellitus. Central nervous system may be considered as the conductor of an orchestra implicating many peripheral organs involved in these homeostatic processes. However, brain is mainly a glucose-dependent organ, which can be damaged by both hypoglycaemia and hyperglycaemia. Hypoglycaemia unawareness is a major problem in clinical practice and is associated with an increased risk of coma. Stroke is another acute complication associated with diabetes mellitus, especially in elderly people, and control of glucose level in this emergency situation remains challenging. The prognosis of stroke is worse in diabetic patients and both the prevention management of at risk patients should be improved. Finally, chronic diabetic encephalopathies, which may lead to cognitive dysfunction and even dementia, are also recognized. They may result from recurrent hypoglycaemia and/or from chronic hyperglycaemia leading to cerebral vascular damages. Functional imaging is of interest to explore diabetes-associated cerebral abnormalities. Thus, the intimate relationship between brain and diabetes is increasingly acknowledged in both research and clinical practice. Key-words

Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance

“…Plasma concentration of fructosamine indicates the amount of glycated protein and is considered a good index of glucose levels over a preceding period of 2-3 weeks; in our particular case of suckling piglets, this parameter may be even more reliable that a single-point glucose determination. Thus, these results would indicate a certain impairment of glucose regulation, possibly related to increases in fat-content because adiposity increases insulin resistance in human young individuals (Elder et al 2006, Scheen 2010.…”

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

“…A severe hyperglycemia in DM1, mild hyperglycemia typical of DM2, and recurrent hypoglycemia induced by inadequate insulin therapy are the major factors responsible for the development of CNS complications in DM. The brain is mainly a glucose-dependent organ, which can be damaged by hyper-as well as by hypoglycemia (Scheen, 2010). Being a major problem in clinical practice, hypoglycemia unawareness is associated with an increased risk of coma.…”

“…The disturbances of neuronal glucose transport and metabolism in hyperglycemia are similar to those in hypoglycemia and also induce neuronal damages and CNS disorders. For example, chronic diabetic encephalopathy leading to cognitive dysfunctions and dementia may be the result of recurrent hypoglycaemia and/or chronic hyperglycaemia, both inducing cerebral vascular damages (Scheen, 2010). A new view of the nature and pathogenesis of DM-induced cerebral complications shared by many specialists nowadays has been prompted by the results of study of functional activity of hormonal signaling systems regulated by insulin, insulin-like growth factor-1 (IGF-1), leptin, biogenic amines, purines, glutamate, and peptide hormones controlling the fundamental processes in the neuronal and glial cells.…”

Cibler la voie métabolique du cortisol comme action thérapeutique dans le diabète de type 2

“…Par ailleurs, il existe certaines similitudes entre les complications liées au diabète et celles liées à l'âge avec, outre les maladies vasculaires, une augmentation des pathologies neurodégénératives [40]. Le cerveau joue un rôle central dans le contrôle des régulations métaboliques [40], et la présence de la 11βHSD1 dans l'hypothalamus suggère que cette enzyme pourrait jouer un rôle dans le contrôle de l'appétit [11]. La présence de la 11βHSD1 dans le cerveau est connue depuis au moins une vingtaine d'années [12], et son rôle dans certaines anomalies du fonctionnement cérébral est suspectée [41].…”