Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Thorens, Bernard

doi:10.1038/ijo.2008.208

Cited by 61 publications

(53 citation statements)

References 117 publications

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“…These organs and tissues have major roles in the use and storage of nutrients in the form of glycogen or triglycerides and in the release of glucose or free fatty acids into the blood, in periods of metabolic needs [18]. These mechanisms are tightly regulated by hormonal and nervous signals, which are generated by specialized cells that detect variations in blood glucose or lipid concentrations.…”

Section: Cns Orchestrates Energy and Glucose Homeostasismentioning

confidence: 99%

“…Work from several laboratories has explored the physiological role of glucose as a signal that regulates these homeostatic processes and has tested the hypothesis that the mechanism of glucose sensing that controls insulin secretion by the pancreatic B cells is also used by other cell types. These mechanisms integrate signals from other nutrients such as lipids and their deregulation may initiate metabolic diseases [18].…”

Section: Cns Orchestrates Energy and Glucose Homeostasismentioning

confidence: 99%

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

Scheen

2010

Diabetes & Metabolism

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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

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Section: Cns Orchestrates Energy and Glucose Homeostasismentioning

confidence: 99%

Section: Cns Orchestrates Energy and Glucose Homeostasismentioning

confidence: 99%

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

Scheen

2010

Diabetes & Metabolism

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“…Ghrelin is a peptide secreted primarily by the stomach and appears to increase appetite (8,9). Glucose is hypothesized to play a role in meal initiation, because feeding is usually preceded by a decrease in blood glucose concentrations (10)(11)(12)(13). Glucose triggers insulin secretion by the b cells of the pancreatic islets (10,11).…”

Section: Introductionmentioning

confidence: 99%

Changes in gut hormone and glucose concentrations in relation to hunger and fullness

Lemmens¹,

Martens²,

Kester³

et al. 2011

The American Journal of Clinical Nutrition

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Background: The search for biomarkers of appetite is very active. Objectives: The aims were to compare dynamics of hunger and fullness ratings on a visual analog scale (VAS) with dynamics of glucagon-like peptide 1, peptide tyrosine-tyrosine, ghrelin, glucose, and insulin concentrations throughout different meal patterns-and thus different timings of nutrient delivery to the gut-by using a statistical approach that focuses on within-subject relations of these observations and to investigate whether appetite ratings are synchronized with or lag behind or in front of changes in hormone and glucose concentrations. Design: Subjects (n = 38) with a mean (6SD) age of 24 6 6 y and BMI (in kg/m 2 ) of 25.1 6 3.1 came to the university twice for consumption of a 4-course lunch in 0.5 or 2 h (randomized crossover design). Per subject regression slopes and R 2 values of VAS scores on hormone and glucose concentrations were calculated. We tested whether the means of the slopes were different from zero. Regarding possible lags in the relations, the analyses were repeated with VAS scores related to hormone and glucose concentrations of the relevant previous and following measurement periods. Results: VAS scores and hormone and glucose concentrations changed synchronously (P , 0.005, R 2 = 0.4-0.7). Changes in ghrelin concentrations lagged behind (10-30 min) changes in hunger scores (P , 0.005, R 2 = 0.7) and insulin concentrations (P , 0.005, R 2 = 0.6), which suggests a role for insulin as a possible negative regulator of ghrelin. No major differences in slopes and R 2 values were found between the meal patterns. Conclusions: This method may be useful for understanding possible differences in relations between VAS scores and hormone and glucose concentrations between subjects or conditions. Yet, the reported explained variation of 40% to 70% seems to be too small to use hormone and glucose concentrations as appropriate biomarkers for appetite, at least at the individual level and probably at the group level. This study started in 2007, which means that it was not registered as a clinical trial.Am J Clin Nutr 2011;94:717-25.

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“…In fasted Glut2-deficient mice, intracerebroventricular glucose injection failed to reduce orexigenic NPY and to induce anorexigenic POMC expression [92]. These data indicate that GLUT2 is required for the physiological control of feeding by glucose.…”

Section: Glucose Sensingmentioning

confidence: 75%

Control of metabolism by nutrient-regulated nuclear receptors acting in the brain

Bantubungi¹,

Prawitt²,

Staels³

2012

The Journal of Steroid Biochemistry and Molecular Biology

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Today, we are witnessing a rising incidence of obesity worldwide. This increase is due to a sedentary life style, an increased caloric intake and a decrease in physical activity. Obesity contributes to the appearance of type 2 diabetes, dyslipidemia and cardiovascular complications due to atherosclerosis, and nephropathy. Therefore, the development of new therapeutic strategies may become a necessity. Given the metabolism controlling properties of nuclear receptors in peripheral organs (such as liver, adipose tissues, pancreas) and their implication in various processes underlying metabolic diseases, they constitute interesting therapeutic targets for obesity, dyslipidemia, cardiovascular disease and type 2 diabetes. The recent identification of the central nervous system as a player in the control of peripheral metabolism opens new avenues to our understanding of the pathophysiology of obesity and type 2 diabetes and potential novel ways to treat these diseases. While the metabolic functions of nuclear receptors in peripheral organs have been extensively investigated, little is known about their functions in the brain, in particular with respect to brain control of energy homeostasis. This review provides an overview of the relationships between nuclear receptors in the brain, mainly at the hypothalamic level, and the central regulation of energy homeostasis. In this context, we will particularly focus on the role of PPARα, PPARγ, LXR and Rev-erb.

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Glucose sensing and the pathogenesis of obesity and type 2 diabetes

Cited by 61 publications

References 117 publications

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

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

Changes in gut hormone and glucose concentrations in relation to hunger and fullness

Control of metabolism by nutrient-regulated nuclear receptors acting in the brain

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