The metabolic impact of small intestinal nutrient sensing

AbstractThe gastrointestinal tract maintains energy and glucose homeostasis, in part through nutrient-sensing and subsequent signaling to the brain and other tissues. In this review, we highlight the role of small intestinal nutrient-sensing in metabolic homeostasis, and link high-fat feeding, obesity, and diabetes with perturbations in these gut-brain signaling pathways. We identify how lipids, carbohydrates, and proteins, initiate gut peptide release from the enteroendocrine cells through small intestinal sensing pathways, and how these peptides regulate food intake, glucose tolerance, and hepatic glucose production. Lastly, we highlight how the gut microbiota impact small intestinal nutrient-sensing in normal physiology, and in disease, pharmacological and surgical settings. Emerging evidence indicates that the molecular mechanisms of small intestinal nutrient sensing in metabolic homeostasis have physiological and pathological impact as well as therapeutic potential in obesity and diabetes.

Download Full-text

Upper Small Intestinal Fatty Acid Sensing Improves Glucose Tolerance Through Suppression of Hepatic Glucose Production

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2015.09.079 ◽

2015 ◽

Vol 39 (6) ◽

pp. 547

Author(s):

Paige V. Bauer ◽

Sophie C. Hamr ◽

Frank A. Duca ◽

Brittany A. Rasmussen ◽

Tony K.T. Lam

Keyword(s):

Fatty Acid ◽

Glucose Tolerance ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Hepatic Glucose ◽

Small Intestinal ◽

Fatty Acid Sensing

Download Full-text

Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90887.2008 ◽

2009 ◽

Vol 296 (3) ◽

pp. E415-E421 ◽

Cited By ~ 90

Author(s):

Safina Ali ◽

Daniel J. Drucker

Keyword(s):

Type 2 Diabetes ◽

Therapeutic Potential ◽

Receptor Gene ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Glucagon Receptor ◽

Hepatic Glucose ◽

Extrahepatic Tissues ◽

Glucagon Receptor Gene

Glucagon is secreted from the α-cells of the pancreatic islets and regulates glucose homeostasis through modulation of hepatic glucose production. As elevated glucagon levels contribute to the pathophysiology of hyperglycemia in subjects with type 2 diabetes, reduction of glucagon receptor gene (Gcgr) activity represents a potential target for the treatment of T2DM. Herein, we review current concepts of glucagon action in hepatic and extrahepatic tissues and evaluate the therapeutic potential, mechanisms of action, and safety of reducing Gcgr signaling for the treatment of T2DM.

Download Full-text

Upper Small Intestinal Protein Sensing Improves Glucose Tolerance Through Suppression of Hepatic Glucose Production

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2015.09.061 ◽

2015 ◽

Vol 39 (6) ◽

pp. 542

Author(s):

Sophie Hamr ◽

Brittany A. Rasmussen ◽

Paige V. Bauer ◽

Frank A. Duca ◽

Tony K.T. Lam

Keyword(s):

Glucose Tolerance ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Protein Sensing ◽

Hepatic Glucose ◽

Intestinal Protein ◽

Small Intestinal

Download Full-text

Nutritional Factors in Central Metabolic Regulation

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/v10046-012-0002-3 ◽

2012 ◽

Vol 66 (3) ◽

pp. 96-100

Author(s):

Alfrēds Jānis Sīpols

Keyword(s):

Negative Feedback ◽

Metabolic Regulation ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Pharmacological Intervention ◽

Mass Mobilization ◽

Metabolic Processes ◽

Hepatic Glucose ◽

Regulate Food Intake ◽

Treatment Of Obesity

Abstract The control of metabolism by direct negative feedback of macronutrients detected centrally has been until recently an attractive, though unconfirmed, hypothesis in the homeostatic model of energy regulation. Research advances in the last decade have greatly expanded our knowledge of how circulating carbohydrates, lipids, and proteins, reflecting amounts of recently ingested macronutrients, are detected in hypothalamic areas to not only regulate food intake, but also direct metabolic processes responsible for energy balance and anabolic pathways. For example, plasma glucose sensed centrally is a major regulator of hepatic glucose production, a process most likely mediated by ATP-sensitive potassium channels. More surprising, circulating lipids detected by hypothalamic structures also act as potent negative feedback regulators of glucose mobilization in the liver, independent of their peripheral detection in the intestines. Finally, central detection of circulating postprandial leucine levels has been shown to decrease abdominal fat mass mobilization and thermogenesis. These findings are consistent with the hypothesis that recognition of macronutrients directly by hypothalamic receptors plays a pivotal role in central regulation of metabolic processes. Moreover, the elucidated mechanisms suggest promising potential sites for pharmacological intervention in the treatment of obesity, already at epidemic proportions, although our modern environment is clearly the major cause.

Download Full-text